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Baskaran SP, Ranganathan G, Sahoo AK, Kumar K, Amaresan J, Ramesh K, Vivek-Ananth RP, Samal A. sCentInDB: a database of essential oil chemical profiles of Indian medicinal plants. Mol Divers 2025:10.1007/s11030-025-11215-5. [PMID: 40343630 DOI: 10.1007/s11030-025-11215-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2025] [Accepted: 05/03/2025] [Indexed: 05/11/2025]
Abstract
Essential oils are complex mixtures of volatile compounds produced by aromatic plants and widely used in personal care, food flavoring, and pharmaceutical industry due to their odor and therapeutic properties. As a high-value and low-volume organic product, optimizing plant yield and modifying composition by leveraging knowledge on chemical profiles of essential oils can lead to enhanced bioproducts. Additionally, overharvesting of wild medicinal plants, especially in India, threatens biodiversity. Essential oil profiles of such plants can help regulate their exploitation. Here, we present sCentInDB, a manually curated FAIR-compliant DataBase of Essential oil Chemical profiles of Medicinal plants of India, compiled from published literature. sCentInDB contains data on 554 Indian medicinal plants at the plant part level, encompassing 2170 essential oil profiles, 3420 chemicals, 471 plant-part-therapeutic use associations, 120 plant-part-odor associations, and 218 plant-part-color associations. sCentInDB also compiles metadata such as sample location, isolation, and analysis methods. Subsequently, an extensive analysis of the chemical space in sCentInDB was performed. By constructing a chemical similarity network, terpenoids were found to be distributed across the network, indicating greater structural diversity. Moreover, a comparison of the scaffold diversity of chemicals in sCentInDB was performed against three other aroma libraries using cyclic system retrieval curves. Altogether, sCentInDB will serve as a valuable resource for researchers working on plant volatiles and employing genetic engineering to enhance oil yield and composition. Further, sCentInDB will aid in the establishment of quality standards for essential oils and provide vital insights for therapeutic and perfumery applications. sCentInDB is accessible at https://cb.imsc.res.in/scentindb/ .
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Affiliation(s)
- Shanmuga Priya Baskaran
- The Institute of Mathematical Sciences (IMSc), Chennai, 600113, India
- Homi Bhabha National Institute (HBNI), Mumbai, 400094, India
| | | | - Ajaya Kumar Sahoo
- The Institute of Mathematical Sciences (IMSc), Chennai, 600113, India
- Homi Bhabha National Institute (HBNI), Mumbai, 400094, India
| | - Kishan Kumar
- The Institute of Mathematical Sciences (IMSc), Chennai, 600113, India
| | | | | | - R P Vivek-Ananth
- The Institute of Mathematical Sciences (IMSc), Chennai, 600113, India
- Homi Bhabha National Institute (HBNI), Mumbai, 400094, India
- Buck Institute for Research on Aging, Novato, CA, USA
| | - Areejit Samal
- The Institute of Mathematical Sciences (IMSc), Chennai, 600113, India.
- Homi Bhabha National Institute (HBNI), Mumbai, 400094, India.
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Rolim TDS, Sampaio ALF, Mazzei JL, Moreira DL, Siani AC. Synthesis, Bioproduction and Bioactivity of Perillic Acid-A Review. Molecules 2025; 30:528. [PMID: 39942631 PMCID: PMC11820084 DOI: 10.3390/molecules30030528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Revised: 01/21/2025] [Accepted: 01/22/2025] [Indexed: 02/16/2025] Open
Abstract
Perillic acid (PA) is a limonene derivative in which the exocyclic methyl is oxidized to a carboxyl group. Although endowed with potential anticancer activity, PA has been much less explored regarding its biological properties than analogous compounds such as perillyl alcohol, perillaldehyde, or limonene itself. PA is usually described in mixture with alcohols and ketones produced in the oxidation of monoterpenes, with relatively few existing reports focusing on the PA molecule. This study provides a comprehensive review of PA, addressing its origin, the processes of obtaining it through organic synthesis and biotransformation, and the pharmacological tests in which it is either the lead compound or reference for in vitro efficacy in experimental models. Although feasible and generally poorly yielded, the synthesis of PA from limonene requires multiple steps and the use of unusual catalysts. The most economical process involves using (-)-β-pinene epoxide as the starting material, ending up with (-)-PA. On the other hand, some bacteria and yeasts are successful in producing, exclusively or at satisfactory purity level, PA from limonene or a few other monoterpenes, through environmentally friendly approaches. The compiled data revealed that, with few exceptions, most reports on PA bioactivity are related to its ability to interfere with the prenylation process of oncogenic proteins, an essential step for the growth and dissemination of cancer cells. The present survey reveals that there is still a vast field to disclose regarding the obtaining and scaling of PA via the fermentative route, as well as extending prospective studies on its properties and possible pharmacological applications, especially in the preclinical oncology field.
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Affiliation(s)
- Thaís de Souza Rolim
- Institute of Drug Technology, Fiocruz, Sizenando Nabuco St. 100, Manguinhos, Rio de Janeiro 21041-250, RJ, Brazil; (T.d.S.R.); (A.L.F.S.); (J.L.M.)
| | - André Luiz Franco Sampaio
- Institute of Drug Technology, Fiocruz, Sizenando Nabuco St. 100, Manguinhos, Rio de Janeiro 21041-250, RJ, Brazil; (T.d.S.R.); (A.L.F.S.); (J.L.M.)
| | - José Luiz Mazzei
- Institute of Drug Technology, Fiocruz, Sizenando Nabuco St. 100, Manguinhos, Rio de Janeiro 21041-250, RJ, Brazil; (T.d.S.R.); (A.L.F.S.); (J.L.M.)
| | - Davyson Lima Moreira
- Institute of Drug Technology, Fiocruz, Sizenando Nabuco St. 100, Manguinhos, Rio de Janeiro 21041-250, RJ, Brazil; (T.d.S.R.); (A.L.F.S.); (J.L.M.)
- Rio de Janeiro Botanical Garden Research Institute, Pacheco Leão St. 915, Jardim Botânico, Rio de Janeiro 22460-030, RJ, Brazil
| | - Antonio Carlos Siani
- Institute of Drug Technology, Fiocruz, Sizenando Nabuco St. 100, Manguinhos, Rio de Janeiro 21041-250, RJ, Brazil; (T.d.S.R.); (A.L.F.S.); (J.L.M.)
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Kutyła M, Pięt M, Stankevič M, Junka A, Brożyna M, Dudek B, Paduch R, Trytek M. Oxidation of myrtenol to myrtenal epoxide in a porphyrin-based photocatalytic system - A novel terpene alcohol derivative with antimicrobial and anticancer properties. Bioorg Chem 2025; 154:108047. [PMID: 39708555 DOI: 10.1016/j.bioorg.2024.108047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Revised: 12/06/2024] [Accepted: 12/07/2024] [Indexed: 12/23/2024]
Abstract
Biomimetic catalysis using porphyrins enables gentle oxidation of terpenes with molecular oxygen and light. This study explores the photooxidation of (-)-myrtenol under visible light to synthesize new terpenoid products with promising biological activity. Among the porphyrins tested, tetraphenylporphyrin (H2TPP) exhibited the highest catalytic efficiency and stability in chloroform, producing myrtenal epoxide (ME) as the main product (with a molar conversion of myrtenol of 66.2 %), confirmed by NMR and MS analyses. Other substrates, i.e. perillyl alcohol and trans-pinocarveol, did not yield redox products. The antimicrobial activity of ME was assessed against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans using Disk Diffusion, Minimal Inhibitory Concentration, and Minimal Biofilm Eradication Concentration assays (using liquid ME) and the Quantitative Assay for Measuring the Antibiofilm Activity of Volatile Compounds (using volatile ME). Overall, ME displayed higher antimicrobial activity than myrtenol in the majority of the tests applied. The strongest effects were observed against C. albicans, followed by S. aureus, while the weakest activity was exhibited against Gram-negative bacteria. ME also showed cytotoxic effects on human colorectal cancer cells (HT-29) with significantly higher biological activity than that of (-)-myrtenol. Notably, ME at lower concentrations (5-50 µg/ml) promoted proliferation of normal cells while inhibiting the viability and proliferation of cancer cells. Porphyrin-based photooxidation is a sustainable method for converting biorenewable terpene feedstocks into new compounds that can be used in cancer treatment and antimicrobial therapy.
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Affiliation(s)
- Mateusz Kutyła
- Department of Industrial and Environmental Microbiology, Faculty of Biology and Biotechnology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland
| | - Mateusz Pięt
- Department of Virology and Immunology, Faculty of Biology and Biotechnology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland
| | - Marek Stankevič
- Department of Organic Chemistry and Crystallochemistry, Faculty of Chemistry, Institute of Chemistry Sciences, Maria Curie-Skłodowska University, Gliniana 33, 20-614 Lublin, Poland
| | - Adam Junka
- Platform for Unique Models Application, Department of Pharmaceutical Microbiology and Parasitology, Wroclaw Medical University, Wrocław, Poland
| | - Malwina Brożyna
- Platform for Unique Models Application, Department of Pharmaceutical Microbiology and Parasitology, Wroclaw Medical University, Wrocław, Poland
| | - Bartłomiej Dudek
- Platform for Unique Models Application, Department of Pharmaceutical Microbiology and Parasitology, Wroclaw Medical University, Wrocław, Poland
| | - Roman Paduch
- Department of Virology and Immunology, Faculty of Biology and Biotechnology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland
| | - Mariusz Trytek
- Department of Industrial and Environmental Microbiology, Faculty of Biology and Biotechnology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland.
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Batista Brochado AC, de Moraes JA, Rodrigues de Oliveira B, De Souza Lima VH, Mariano ED, Karande S, Romasco T, Leite PEC, Mourão CF, Gomes Alves G. Metabolic and Regulatory Pathways Involved in the Anticancer Activity of Perillyl Alcohol: A Scoping Review of In Vitro Studies. Cancers (Basel) 2024; 16:4003. [PMID: 39682189 PMCID: PMC11640718 DOI: 10.3390/cancers16234003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Revised: 11/25/2024] [Accepted: 11/27/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND/OBJECTIVES Perillyl alcohol (POH), a plant-derived compound, has demonstrated anti-tumor activity across various human cancers. Understanding the regulatory pathways through which POH exerts its effects is crucial for identifying new therapeutic opportunities and exploring potential drug repositioning strategies. Therefore, this scoping review aims to provide a comprehensive overview of the metabolic and regulatory pathways involved in the anticancer effects of POH, based on in vitro evidence. METHODS Following the PRISMA-ScR 2018 guidelines, a systematic search was conducted in the PUBMED, Web of Science, and Scopus databases. RESULTS A total of 39 studies were included, revealing that POH exerts its biological effects by modulating several pathways, including the regulation of cyclins, CDKs, and p21, thereby affecting cell cycle progression. It inhibits growth and promotes cell death by attenuating AKT phosphorylation, reducing PARP-1 activity, increasing caspase activity and the FAS receptor and its ligand FASL. Additionally, POH reduces ERK phosphorylation, inhibits RAS protein isoprenylation, and decreases Na/K-ATPase activity. CONCLUSIONS In conclusion, this review delineates the key regulatory pathways responsible for mediating the biological effects of POH in cancer.
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Affiliation(s)
- Ana Carolina Batista Brochado
- Post-Graduation Program in Science & Biotechnology, Institute of Biology, Fluminense Federal University, Niteroi 24220-900, Brazil
| | - Júlia Alves de Moraes
- Clinical Research Unit, Antonio Pedro University Hospital, Fluminense Federal University, Niteroi 24020-140, Brazil
| | - Bruna Rodrigues de Oliveira
- Clinical Research Unit, Antonio Pedro University Hospital, Fluminense Federal University, Niteroi 24020-140, Brazil
| | - Victor Hugo De Souza Lima
- Post-Graduation Program in Science & Biotechnology, Institute of Biology, Fluminense Federal University, Niteroi 24220-900, Brazil
| | | | - Sachin Karande
- Dental Research Division, Department of Periodontology and Oral Implantology, Fluminense Federal University, Niteroi 21941-617, Brazil
| | - Tea Romasco
- Division of Dental Research Administration, Tufts University School of Dental Medicine, Boston, MA 02111, USA
- Department of Medical, Oral and Biotechnological Sciences, Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
| | - Paulo Emilio Correa Leite
- Post-Graduation Program in Science & Biotechnology, Institute of Biology, Fluminense Federal University, Niteroi 24220-900, Brazil
| | - Carlos Fernando Mourão
- Department of Basic and Clinical Translational Sciences, Tufts University School of Dental Medicine, Boston, MA 02111, USA
| | - Gutemberg Gomes Alves
- Post-Graduation Program in Science & Biotechnology, Institute of Biology, Fluminense Federal University, Niteroi 24220-900, Brazil
- Clinical Research Unit, Antonio Pedro University Hospital, Fluminense Federal University, Niteroi 24020-140, Brazil
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Zhang L, Wang G, Li Z, Yang J, Li H, Wang W, Li Z, Li H. Molecular pharmacology and therapeutic advances of monoterpene perillyl alcohol. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 132:155826. [PMID: 38897045 DOI: 10.1016/j.phymed.2024.155826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Revised: 02/20/2024] [Accepted: 06/12/2024] [Indexed: 06/21/2024]
Abstract
BACKGROUND Perillyl alcohol (POH) is a aroma monoterpene commonly obtained from various plants' essential oil. Recently, increasing researches have demonstrated that POH may be useful, not only as flavor compound, but also as bioactive molecule because of a variety of biological activities. PURPOSE The aim of this review is to summarize the production, pharmacological activities and molecular mechanism, active derivatives, toxicity and parmacokinetics, and industrial application of POH. METHODS A systematic search of published articles up to January 2024 in Web of Science, China Knowledge Network, and PubMed databases is conducted using the following keywords: POH, POH derivatives, biological or pharmacological, production or synthesis, pharmacokinetics, toxicity and application. RESULTS Biotechnological production is considered to be a potential alternative approach to generate POH. POH provides diverse pharmacological benefits, including anticancer, antimicrobial, insecticidal, antioxidant, anti-inflammatory, hypotensive, vasorelaxant, antinociceptive, antiasthmatic, hepatoprotective effects, etc. The underlying mechanisms of action include modulation of NF-κB, JNK/c-Jun, Notch, Akt/mTOR, PI3K/Akt/eNOS, STAT3, Nrf2 and ERS response pathways, mitigation of mitochondrial dysfunction and membrane integrity damage, and inhibition of ROS accumulation, pro-inflammatory cytokines release and NLRP3 activation. What's more, the proteins or genes influenced by POH against diseases refer to Bax, Bcl-2, cyclin D1, CDK, p21, p53, HIF-1α, AP-1, caspase-3, M6P/IGF2R, PARP, VEGF, etc. Some clinical studies report that intranasal delivery of POH is a safe and effective treatment for cancer, but further clinical investigations are needed to confirm other health benefits of POH in human healthy. Depending on these health-promoting properties together with desirable flavor and safety, POH can be employed as dietary supplement, preservative and flavor additive in food and cosmetic fields, as building block in synthesis fields, as anticancer drug in medicinal fields, and as pesticides and herbicides in agricultural fields. CONCLUSION This review systematically summarizes the recent advances in POH and highlights its therapeutic effects and potential mechanisms as well as the clinical settings, which is helpful to develop POH into functional food and new candidate drug for prevention and management of diseases. Future studies are needed to conduct more biological activity studies of POH and its derivatives, and check their clinical efficacy and potential side effects.
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Affiliation(s)
- Lulu Zhang
- College of Food Science and Technology, Henan University of Technology, Zhengzhou, Henan 450001, PR China; Henan Province Wheat-flour Staple Food Engineering Technology Research Centre, Zhengzhou, Henan 450001, PR China.
| | - Guoguo Wang
- College of Food Science and Technology, Henan University of Technology, Zhengzhou, Henan 450001, PR China; Henan Province Wheat-flour Staple Food Engineering Technology Research Centre, Zhengzhou, Henan 450001, PR China
| | - Zehao Li
- College of Food Science and Technology, Henan University of Technology, Zhengzhou, Henan 450001, PR China; Henan Province Wheat-flour Staple Food Engineering Technology Research Centre, Zhengzhou, Henan 450001, PR China
| | - Jinchu Yang
- Technology Center, China Tobacco Henan Industrial Co., Ltd., Zhengzhou, Henan 450000, PR China.
| | - Haoliang Li
- Technology Center, China Tobacco Henan Industrial Co., Ltd., Zhengzhou, Henan 450000, PR China
| | - Wanying Wang
- College of Food Science and Technology, Henan University of Technology, Zhengzhou, Henan 450001, PR China; Henan Province Wheat-flour Staple Food Engineering Technology Research Centre, Zhengzhou, Henan 450001, PR China
| | - Zhijian Li
- College of Food Science and Technology, Henan University of Technology, Zhengzhou, Henan 450001, PR China; Henan Province Wheat-flour Staple Food Engineering Technology Research Centre, Zhengzhou, Henan 450001, PR China
| | - Hua Li
- College of Food Science and Technology, Henan University of Technology, Zhengzhou, Henan 450001, PR China; Henan Province Wheat-flour Staple Food Engineering Technology Research Centre, Zhengzhou, Henan 450001, PR China.
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Zagórska-Dziok M, Nowak A, Zgadzaj A, Oledzka E, Kędra K, Wiącek AE, Sobczak M. New Polymeric Hydrogels with Cannabidiol and α-Terpineol as Potential Materials for Skin Regeneration-Synthesis and Physicochemical and Biological Characterization. Int J Mol Sci 2024; 25:5934. [PMID: 38892121 PMCID: PMC11173307 DOI: 10.3390/ijms25115934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 05/26/2024] [Accepted: 05/27/2024] [Indexed: 06/21/2024] Open
Abstract
Dermatology and cosmetology currently prioritize healthy, youthful-looking skin. As a result, research is being conducted worldwide to uncover natural substances and carriers that allow for controlled release, which could aid in the battle against a variety of skin illnesses and slow the aging process. This study examined the biological and physicochemical features of novel hydrogels containing cannabidiol (CBD) and α-terpineol (TER). The hydrogels were obtained from ε-caprolactone (CL) and poly(ethylene glycol) (PEG) copolymers, diethylene glycol (DEG), poly(tetrahydrofuran) (PTHF), 1,6-diisocyanatohexane (HDI), and chitosan (CHT) components, whereas the biodegradable oligomers were synthesized using the enzyme ring-opening polymerization (e-ROP) method. The in vitro release rate of the active compounds from the hydrogels was characterized by mainly first-order kinetics, without a "burst release". The antimicrobial, anti-inflammatory, cytotoxic, antioxidant, and anti-aging qualities of the designed drug delivery systems (DDSs) were evaluated. The findings indicate that the hydrogel carriers that were developed have the ability to scavenge free radicals and impact the activity of antioxidant enzymes while avoiding any negative effects on keratinocytes and fibroblasts. Furthermore, they have anti-inflammatory qualities by impeding protein denaturation as well as the activity of proteinase and lipoxygenase. Additionally, their ability to reduce the multiplication of pathogenic bacteria and inhibit the activity of collagenase and elastase has been demonstrated. Thus, the developed hydrogel carriers may be effective systems for the controlled delivery of CBD, which may become a valuable tool for cosmetologists and dermatologists.
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Affiliation(s)
- Martyna Zagórska-Dziok
- Department of Technology of Cosmetic and Pharmaceutical Products, Faculty of Medicine, University of Information Technology and Management in Rzeszow, 2 Sucharskiego St., 35-225 Rzeszow, Poland;
| | - Anna Nowak
- Department of Cosmetic and Pharmaceutical Chemistry, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland;
| | - Anna Zgadzaj
- Department of Environmental Health Sciences, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha St., 02-097 Warsaw, Poland;
| | - Ewa Oledzka
- Department of Pharmaceutical Chemistry and Biomaterials, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland;
| | - Karolina Kędra
- Institute of Physical Chemistry, Polish Academy of Sciences, 44/52 Kasprzaka St., 01-224 Warsaw, Poland;
| | - Agnieszka Ewa Wiącek
- Department of Interfacial Phenomena, Faculty of Chemistry, Maria Curie-Skłodowska University, pl. Sq. M. Curie-Skłodowskiej 3, 20-031 Lublin, Poland;
| | - Marcin Sobczak
- Department of Pharmaceutical Chemistry and Biomaterials, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland;
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Citrus Essential Oils in Aromatherapy: Therapeutic Effects and Mechanisms. Antioxidants (Basel) 2022; 11:antiox11122374. [PMID: 36552586 PMCID: PMC9774566 DOI: 10.3390/antiox11122374] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 11/22/2022] [Accepted: 11/25/2022] [Indexed: 12/05/2022] Open
Abstract
Citrus is one of the main fruit crops cultivated in tropical and subtropical regions worldwide. Approximately half (40-47%) of the fruit mass is inedible and discarded as waste after processing, which causes pollution to the environment. Essential oils (EOs) are aromatic compounds found in significant quantities in oil sacs or oil glands present in the leaves, flowers, and fruit peels (mainly the flavedo part). Citrus EO is a complex mixture of ~400 compounds and has been found to be useful in aromatic infusions for personal health care, perfumes, pharmaceuticals, color enhancers in foods and beverages, and aromatherapy. The citrus EOs possess a pleasant scent, and impart relaxing, calming, mood-uplifting, and cheer-enhancing effects. In aromatherapy, it is applied either in message oils or in diffusion sprays for homes and vehicle sittings. The diffusion creates a fresh feeling and enhances relaxation from stress and anxiety and helps uplifting mood and boosting emotional and physical energy. This review presents a comprehensive outlook on the composition, properties, characterization, and mechanism of action of the citrus EOs in various health-related issues, with a focus on its antioxidant properties.
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Dudek T, Marć M, Zabiegała B. Chemical Composition of Atmospheric Air in Nemoral Scots Pine Forests and Submountainous Beech Forests: The Potential Region for the Introduction of Forest Therapy. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:15838. [PMID: 36497918 PMCID: PMC9736340 DOI: 10.3390/ijerph192315838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Revised: 11/24/2022] [Accepted: 11/25/2022] [Indexed: 06/17/2023]
Abstract
Studies show that forests are one of the main recreational destinations. This can be explained by their beneficial effects on the health of their visitors, which can be attributed to compounds from the terpene group. The aim of this research was to determine the chemical composition of air in the interiors of Nemoral Scots pine forests and submountainous beech forests, with the determination of compounds of the terpene group. Samples of organic compounds present in the air were collected with the use of Tenax TA sorbent tubes. The process of separation, identification, and determination of the extracted organic compounds was carried out with the use of the gas chromatography technique integrated with a flame ionization detector. Additional identification of the extracted compounds was carried out with the use of GC coupled with mass spectrometry. The most abundant group of compounds was the aliphatic hydrocarbons, both saturated (linear and branched) and unsaturated (terpenes). Carbonyl compounds were also found in the collected samples, but they constituted no more than 10% of all compounds present on the chromatograms. The concentrations of terpenes and terpenoids in the forest atmosphere varied from 10 to 74 µg·m-3, representing on average 33% of the total volatile organic compounds.
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Affiliation(s)
- Tomasz Dudek
- Department of Agroecology and Forest Utilization, University of Rzeszów, 35-601 Rzeszów, Poland
| | - Mariusz Marć
- Department of Analytical Chemistry, Faculty of Chemistry, Gdańsk University of Technology, 80-233 Gdańsk, Poland
| | - Bożena Zabiegała
- Department of Analytical Chemistry, Faculty of Chemistry, Gdańsk University of Technology, 80-233 Gdańsk, Poland
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Kamran S, Sinniah A, Abdulghani MAM, Alshawsh MA. Therapeutic Potential of Certain Terpenoids as Anticancer Agents: A Scoping Review. Cancers (Basel) 2022; 14:1100. [PMID: 35267408 PMCID: PMC8909202 DOI: 10.3390/cancers14051100] [Citation(s) in RCA: 83] [Impact Index Per Article: 27.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 01/19/2022] [Accepted: 02/05/2022] [Indexed: 02/01/2023] Open
Abstract
Cancer is a life-threatening disease and is considered to be among the leading causes of death worldwide. Chemoresistance, severe toxicity, relapse and metastasis are the major obstacles in cancer therapy. Therefore, introducing new therapeutic agents for cancer remains a priority to increase the range of effective treatments. Terpenoids, a large group of secondary metabolites, are derived from plant sources and are composed of several isoprene units. The high diversity of terpenoids has drawn attention to their potential anticancer and pharmacological activities. Some terpenoids exhibit an anticancer effect by triggering various stages of cancer progression, for example, suppressing the early stage of tumorigenesis via induction of cell cycle arrest, inhibiting cancer cell differentiation and activating apoptosis. At the late stage of cancer development, certain terpenoids are able to inhibit angiogenesis and metastasis via modulation of different intracellular signaling pathways. Significant progress in the identification of the mechanism of action and signaling pathways through which terpenoids exert their anticancer effects has been highlighted. Hence, in this review, the anticancer activities of twenty-five terpenoids are discussed in detail. In addition, this review provides insights on the current clinical trials and future directions towards the development of certain terpenoids as potential anticancer agents.
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Affiliation(s)
- Sareh Kamran
- Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia; (S.K.); (A.S.)
| | - Ajantha Sinniah
- Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia; (S.K.); (A.S.)
| | - Mahfoudh A. M. Abdulghani
- Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim University, Al Qassim 51911, Saudi Arabia;
| | - Mohammed Abdullah Alshawsh
- Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia; (S.K.); (A.S.)
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10
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Chebet JJ, Ehiri JE, McClelland DJ, Taren D, Hakim IA. Effect of d-limonene and its derivatives on breast cancer in human trials: a scoping review and narrative synthesis. BMC Cancer 2021; 21:902. [PMID: 34362338 PMCID: PMC8349000 DOI: 10.1186/s12885-021-08639-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 07/27/2021] [Indexed: 12/01/2022] Open
Abstract
BACKGROUND D-limonene and its derivatives have demonstrated potential chemopreventive and anticancer activity in preclinical and clinical studies. The aim of this scoping review was to assess and critically appraise current literature on the effect of these bioactive citrus peel compounds on breast cancer in human trials and to identify knowledge gaps for exploration in future studies. METHODS This study followed a scoping review framework. Peer-reviewed journal articles were included if they reported the effect of d-limonene or its derivatives on breast cancer in human subjects. Articles were retrieved from academic databases - PubMed, EMBASE, CINAHL, Web of Science, and Cochrane reviews - and iteratively through review of bibliographies of relevant manuscripts. Titles and abstracts were appraised against the aforementioned inclusion criteria in a first round of screening. Through consensus meetings and full article review by authors, a final set of studies were selected. Results were reported according to the PRISMA extension for scoping reviews. RESULTS Our search strategy yielded 367 records. Following screening and adjudication, five articles reporting on phase 1(n = 2), phase 2 (n = 2) and both trial phases (n = 1) were included as the final dataset for this review. Trials evaluating the effect of d-limonene (n = 2) showed it was well tolerated in subjects. One study (n = 43 participants) showed d-limonene concentrated in breast tissue (mean 41.3 μg/g tissue) and reduction in tumor cyclin D1 expression, which is associated with tumor proliferation arrest. This study did not show meaningful change in serum biomarkers associated with breast cancer, except for a statistically significant increase in insulin-like growth factor-1 (IGF-I) levels. While elevation of IGF-I is associated with increased cancer risk, the clinical implication of this study remains uncertain given its short duration. Trials with perillyl alcohol (n = 3) showed low tolerance and no effect on breast cancer. CONCLUSION This review demonstrated a dearth of clinical studies exploring the effect of d-limonene and its derivatives on breast cancer. Limited literature suggests d-limonene is safe and tolerable in human subjects compared to its derivative, perillyl alcohol. Our review demonstrates the need for additional well-powered placebo-controlled trials that assess d-limonene's efficacy on breast cancer compared to other therapies.
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Affiliation(s)
- Joy J Chebet
- Department of Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, 1295 N Martin Ave, Tucson, AZ, 85724, USA
| | - John E Ehiri
- Department of Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, 1295 N Martin Ave, Tucson, AZ, 85724, USA
| | | | - Douglas Taren
- Department of Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, 1295 N Martin Ave, Tucson, AZ, 85724, USA
| | - Iman A Hakim
- Department of Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, 1295 N Martin Ave, Tucson, AZ, 85724, USA.
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11
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Mekkaoui AA, Ben El Ayouchia H, Anane H, Chahboun R, El Firdoussi L, El Houssame S. Viable route and DFT study for the synthesis of optically active limonaketone: A barely available natural feedstock in Cedrus atlantica. J Mol Struct 2021. [DOI: 10.1016/j.molstruc.2021.130221] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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12
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Ravera M, Gabano E, Zanellato I, Rangone B, Perin E, Ferrari B, Bottone MG, Osella D. Cis,cis,trans-[Pt IVCl 2(NH 3) 2(perillato) 2], a dual-action prodrug with excellent cytotoxic and antimetastatic activity. Dalton Trans 2021; 50:3161-3177. [PMID: 33595015 DOI: 10.1039/d0dt04051g] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Two Pt(iv) conjugates containing one or two molecules of perillic acid (4-isopropenylcyclohexene-1-carboxylic acid), an active metabolite of limonene, were synthesized both with traditional and microwave-assisted methods and characterized. Their antiproliferative activity was tested on a panel of human tumor cell lines. In particular, cis,cis,trans-[PtIVCl2(NH3)2(perillato)2] exhibited excellent antiproliferative and antimetastatic activity on A-549 lung tumor cells at nanomolar concentrations. A number of in vitro biological tests were performed to decipher some aspects of its mechanism of action, including transwell migration and invasion as well as wound healing assay.
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Affiliation(s)
- Mauro Ravera
- Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale, Viale Michel 11, 15121 Alessandria, Italy.
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Dehsheikh AB, Sourestani MM, Dehsheikh PB, Mottaghipisheh J, Vitalini S, Iriti M. Monoterpenes: Essential Oil Components with Valuable Features. Mini Rev Med Chem 2021; 20:958-974. [PMID: 31969098 DOI: 10.2174/1389557520666200122144703] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Revised: 12/01/2019] [Accepted: 01/09/2020] [Indexed: 12/16/2022]
Abstract
Medicinal plants have a wide range of secondary metabolites including monoterpene. These volatile compounds are the main components of essential oils, belonging to the isoprenoid group and possessing valuable features for plants and humans. This review provides comprehensive information on chemical structures and classification of monoterpenes. It describes their biosynthesis pathways and introduces plant families and species rich in noteworthy monoterpenes. Bio-activities, pharmacological and pesticide effects as well as their mechanism of action are reported. Applications of these compounds in various industries are also included.
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Affiliation(s)
- Anahita Boveiri Dehsheikh
- Horticultural Science Department, Faculty of Agriculture, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | | | - Paria Boveiri Dehsheikh
- Horticultural Science Department, Faculty of Agriculture, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Javad Mottaghipisheh
- Department of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
| | - Sara Vitalini
- Department of Agricultural and Environmental Sciences, Milan State University, Milan, Italy
| | - Marcello Iriti
- Department of Agricultural and Environmental Sciences, Milan State University, Milan, Italy
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Kushwaha PP, Singh AK, Shuaib M, Prajapati KS, Vardhan PS, Gupta S, Kumar S. 3-O-(E)-p-Coumaroyl betulinic acid possess anticancer activity and inhibit Notch signaling pathway in breast cancer cells and mammosphere. Chem Biol Interact 2020; 328:109200. [PMID: 32702347 DOI: 10.1016/j.cbi.2020.109200] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Revised: 06/06/2020] [Accepted: 07/13/2020] [Indexed: 02/05/2023]
Abstract
Activation of Notch signaling is associated with tumor aggressiveness, poor clinical outcome and drug resistance in breast cancer patients. Targeting Notch signaling with small molecule inhibitors may be a better strategy for anticancer drug development. We identified 3-O-(E)-p-Coumaroylbetulinic acid (CB) as a lead compound and potent inhibitor of Notch signaling pathway. Treatment of human breast cancer MBA-MD-231 and T47D cells with CB resulted in a dose- and time-dependent inhibition of cell viability and G0/G1-phase cell cycle arrest. This effect was associated with a marked decrease in the expression of cyclin D1 and its activating partner, cyclin-dependent kinase 2 with concomitant increase in cyclin kinase inhibitor p21, operative in G1-phase of the cell cycle. CB treatment induced early apoptosis in breast cancer cells as evident by increase in cleaved caspase-3, decrease in Bcl2 and survivin, surge in reactive oxygen species and disruption of mitochondrial membrane potential. CB treatment altered Notch target genes viz. Hes1, Hey1 and E-cadherin at mRNA and protein level in time-dependent manner along with decrease in Notch promoter activity at IC50 concentration. Furthermore, CB treatment decreased mammosphere formation in MCF-7 cells through down-modulation of the Notch signaling pathway and suppression of self-renewal markers such as c-Myc, SOX-2 and CD44. Our findings demonstrate that CB possess anticancer activity in breast cancer cells and suppresses self-renewal ability in the mammosphere as a result of modulation in cell-cycle machinery, disruption of mitochondrial function, induction of apoptosis, and Notch inhibition.
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Affiliation(s)
- Prem Prakash Kushwaha
- Department of Biochemistry, Central University of Punjab, Bathinda, 151001, Punjab, India
| | - Atul Kumar Singh
- Department of Biochemistry, Central University of Punjab, Bathinda, 151001, Punjab, India
| | - Mohd Shuaib
- Department of Biochemistry, Central University of Punjab, Bathinda, 151001, Punjab, India
| | | | | | - Sanjay Gupta
- Department of Urology, Case Western Reserve University, Cleveland, OH, 44106, USA
| | - Shashank Kumar
- Department of Biochemistry, Central University of Punjab, Bathinda, 151001, Punjab, India.
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15
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Januszewicz K, Kazimierski P, Kosakowski W, Lewandowski WM. Waste Tyres Pyrolysis for Obtaining Limonene. MATERIALS (BASEL, SWITZERLAND) 2020; 13:E1359. [PMID: 32192185 PMCID: PMC7143481 DOI: 10.3390/ma13061359] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 03/06/2020] [Accepted: 03/09/2020] [Indexed: 11/17/2022]
Abstract
This review deals with the technologies of limonene production from waste tyre pyrolysis. Thermal decomposition is attractive for tackling the waste tyre disposal problem, as it enables both: energy to be recovered and limonene to be obtained. This material management recycling of tyres is environmentally more beneficial than the burning of all valuable products, including limonene. Given this recoverability of materials from waste tyres, a comprehensive evaluation was carried out to show the main effect of process conditions (heating rate, temperature, pressure, carrier gas flow rate, and type of volatile residence and process times) for different pyrolytic methods and types of apparatus on the yield of limonene. All the results cited are given in the context of the pyrolysis method and the type of reactor, as well as the experimental conditions in order to avoid contradictions between different researchers. It is shown that secondary and side reactions are very sensitive to interaction with the above-mentioned variables. The yields of all pyrolytic products are also given, as background for limonene, the main product reported in this study.
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Affiliation(s)
- Katarzyna Januszewicz
- Department of Energy Conversion and Storage, Faculty of Chemistry, Gdańsk University of Technology, G. Narutowicza 11/12, PL-80-233 Gdańsk, Poland;
| | - Paweł Kazimierski
- Institute of Fluid-Flow Machinery, Polish Academy of Sciences, Fiszera 14 st., PL-80-231 Gdańsk, Poland;
| | - Wojciech Kosakowski
- Polmos Żyrardów Sp. z o.o. (ul. Mickiewicza 1-3), PL-96-300 Żyrardów, Poland;
| | - Witold M. Lewandowski
- Department of Energy Conversion and Storage, Faculty of Chemistry, Gdańsk University of Technology, G. Narutowicza 11/12, PL-80-233 Gdańsk, Poland;
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16
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AISA can control the inflammatory facet of SASP. Mech Ageing Dev 2020; 186:111206. [DOI: 10.1016/j.mad.2019.111206] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 12/29/2019] [Accepted: 12/30/2019] [Indexed: 12/12/2022]
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17
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Castner E, Dickson M, Mykytyn A, Seeram NP, Henry GE, Vivekanand P. Synthesis and evaluation of apoptotic induction of human cancer cells by ester derivatives of thujone. Med Chem Res 2019. [DOI: 10.1007/s00044-019-02481-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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18
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Natalia AH, Tambunan USF. Screening of terpenoids as potential therapeutics against Zaire ebolavirus infection through pharmacophore-based drug design. F1000Res 2019. [DOI: 10.12688/f1000research.19238.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Backgroud: Ebola virus disease (EVD) has spread to various countries in the world and has caused many deaths. Five different virus species can cause EVD, but the most virulent is Zaire ebolavirus (EBOV). The genome of EBOV includes seven genes that encode proteins playing essential roles in the virus lifecycle. Among these proteins, VP24 plays a vital role in the inhibition of the host cells’ immune system. Therefore, VP24 is a potential target for EVD therapy. In the present study, a potential inhibitor of EBOV VP24 activity was identified through pharmacophore-based drug design. Methods: This research was a in silico study, using pharmacophore based molecular docking simulation to obtain inhibitor candidates. Result: Terpenoids were used as VP24 inhibitor candidates. In particular, 55,979 terpenoids were obtained from the PubChem database. An initial screening based on the toxicity prediction test was performed with DataWarrior software: 3,353 ligands were shown to have a favorable toxicity profile, but only 1,375 among them had suitable pharmacophore features. These ligands were used for pharmacophore-based rigid and flexible molecular docking simulations with PDB ID: 4M0Q, chosen as the crystal structure of EBOV VP24. Six ligands predicted to have strong molecular interactions with EBOV VP24 underwent pharmacological property analysis through various software packages, including DataWarrior, SwissADME, admetSAR, pkCSM, and Toxtree. Conclusions: Taxumairol V was identified as the best candidate for EVD drug therapy via EBOV VP24 inhibition based on its molecular properties, predicted molecular interactions with the target molecule, and predicted pharmacological properties.
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19
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Mukhtar YM, Wang K, Li R, Deng W, Adu-Frimpong M, Zhang H, Zhang K, Gu C, Xu X, Yu J. Novel N-arylamide derivatives of ( S)-perillic acid (( S)-PA): in vitro and in vivo cytotoxicity and antitumor evaluation. RSC Adv 2019; 9:19973-19982. [PMID: 35514731 PMCID: PMC9065563 DOI: 10.1039/c9ra03382c] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Accepted: 06/10/2019] [Indexed: 11/21/2022] Open
Abstract
Hepatocellular carcinoma (HC) and glioblastoma (GBA) are the most commonly aggressive malignant liver and brain tumors. Based on an established method for the synthesis of amide, two novel analogues (4 and 5) of (S)-perillic acid were synthesized and their structures were affirmed using nuclear magnetic resonance spectroscopic analysis. An MTT cytotoxic assay showed that our derivatives (4 and 5) demonstrated a substantial anti-proliferative effect against HC (HepG2) and GBA (U251) cell lines. Particularly, compound 5 showed growth inhibitory (IC50) effects on U251 (IC50 = 3.10 ± 0.12 μg mL-1) and HepG2 cells (IC50 = 1.49 ± 0.43 μg mL-1), which fall within the acceptable standard recommended by the National institute of cancer (Bethesda, MD, USA) for the selection of anticancer drug candidates. Consequently, we assessed the in vivo antitumor and organ/tissue toxicity of 4, 5 and 5-fluorouracil (5-FU) in hepatoma H22-inoculated mice. The results obtained indicated remarkable tumor growth inhibition with no substantial toxicological effects on the mice and the organs/tissues in the treated groups compared well with the control.
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Affiliation(s)
- Yusif Mohammed Mukhtar
- Department of Pharmaceutics and Tissue Engineering, School of Pharmacy, Jiangsu University 301 Xuefu Road Zhenjiang 212001 P. R. China
| | - Kaili Wang
- Department of Pharmaceutics and Tissue Engineering, School of Pharmacy, Jiangsu University 301 Xuefu Road Zhenjiang 212001 P. R. China
| | - Ran Li
- Department of Pharmaceutics and Tissue Engineering, School of Pharmacy, Jiangsu University 301 Xuefu Road Zhenjiang 212001 P. R. China
| | - Wenwen Deng
- Department of Pharmaceutics and Tissue Engineering, School of Pharmacy, Jiangsu University 301 Xuefu Road Zhenjiang 212001 P. R. China
| | - Michael Adu-Frimpong
- Department of Pharmaceutics and Tissue Engineering, School of Pharmacy, Jiangsu University 301 Xuefu Road Zhenjiang 212001 P. R. China
- Department of Basic and Biomedical Sciences, College of Health and Well-Being P. O. Box 9, Kintampo Ghana
| | - Huiyun Zhang
- Department of Pharmaceutics and Tissue Engineering, School of Pharmacy, Jiangsu University 301 Xuefu Road Zhenjiang 212001 P. R. China
| | - Kangyi Zhang
- Department of Pharmaceutics and Tissue Engineering, School of Pharmacy, Jiangsu University 301 Xuefu Road Zhenjiang 212001 P. R. China
| | - Chenlu Gu
- Department of Pharmaceutics and Tissue Engineering, School of Pharmacy, Jiangsu University 301 Xuefu Road Zhenjiang 212001 P. R. China
| | - Ximing Xu
- Department of Pharmaceutics and Tissue Engineering, School of Pharmacy, Jiangsu University 301 Xuefu Road Zhenjiang 212001 P. R. China
| | - Jiangnan Yu
- Department of Pharmaceutics and Tissue Engineering, School of Pharmacy, Jiangsu University 301 Xuefu Road Zhenjiang 212001 P. R. China
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Prakash O, Usmani S, Singh R, Mahapatra DK, Gupta A. Cancer Chemotherapy by Novel Bio-active Natural Products: Looking Towards the Future. CURRENT CANCER THERAPY REVIEWS 2019. [DOI: 10.2174/1573394714666180321151315] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
Cancer is the second leading cause of death globally and accounted for
8.8 million deaths annually in humans. Lung, prostate, colorectal, stomach and liver cancer are the
most common types of cancer in men, while breast, colorectal, lung, cervix and stomach cancer
are the most common among women. Numerous drugs that the US Food and Drug Administration
(FDA) have approved for use in cancer therapy are derived from plants, including taxanes such as
paclitaxel and vinca alkaloids such as vincristine and vinblastine. Still, there is an intense need for
a search for numerous bioactive sources to develop a novel anti-cancer drug to overcome this
chronic disorder. About more than thirty plants derived natural products have been isolated till
date and are currently under clinical trials. As per literature survey from various journals and texts
has been found to be novel medicinal agents from bioactive sources are clinically active against
various types of cancer cells.
Conclusion:
Current review has been highlighted on the novel medicinal agents from plant
sources have potential effects against many types of cancer, which have been supported by clinical
trials. The main findings of these active novel medicinal agents were also summarized and
discussed here.
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Affiliation(s)
- Om Prakash
- Goel Institute of Pharmacy and Sciences, Faizabad Road, Lucknow, Uttar Pradesh, India
| | - Shazia Usmani
- Faculty of Pharmacy, Integral University, Dasauli, Kursi Road, Lucknow, Uttar Pradesh, India
| | - Ruchi Singh
- Goel Institute of Pharmacy and Sciences, Faizabad Road, Lucknow, Uttar Pradesh, India
| | - Debarshi K. Mahapatra
- Department of Pharmaceutical Chemistry, Dadasaheb Balpande College of Pharmacy, Nagpur, Maharashtra, India
| | - Amresh Gupta
- Goel Institute of Pharmacy and Sciences, Faizabad Road, Lucknow, Uttar Pradesh, India
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Vendrusculo V, de Souza VP, M Fontoura LA, M D'Oca MG, Banzato TP, Monteiro PA, Pilli RA, de Carvalho JE, Russowsky D. Synthesis of novel perillyl-dihydropyrimidinone hybrids designed for antiproliferative activity. MEDCHEMCOMM 2018; 9:1553-1564. [PMID: 30288229 PMCID: PMC6151448 DOI: 10.1039/c8md00270c] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/26/2018] [Accepted: 07/27/2018] [Indexed: 12/29/2022]
Abstract
A series of fifteen novel dihydropyrimidinone hybrid compounds were synthesized in good yields via a multicomponent reaction combined with the Huisgen reaction. The antiproliferative activity was investigated against nine tumor cell lines, and four hybrid compounds (TGI < 10 μM) showed promising antiproliferative activity against the tumor cell lines OVCAR-3 (ovarian), UACC-62 (melanoma) and U251 (glioma). Several hybrid compounds assayed have high TGI values (TGI 147.92-507.82) for the human keratinocyte cell line (HaCat), which reveals selectivity to cancer cells.
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Affiliation(s)
- Vinicius Vendrusculo
- Instituto de Química , Universidade Federal do Rio Grande do Sul , Porto Alegre , RS , Brazil .
| | - Vanessa P de Souza
- Instituto de Química , Universidade Federal do Rio Grande do Sul , Porto Alegre , RS , Brazil .
| | - Luiz Antônio M Fontoura
- Fundação da Ciência e Tecnologia do Estado do Rio Grande do Sul , Porto Alegre , RS , Brazil
- PPGEMPS , Universidade Luterana do Brasil , Canoas , RS , Brazil
| | - Marcelo G M D'Oca
- Escola de Química e Alimentos , Universidade Federal do Rio Grande , Rio Grande , RS , Brazil
| | - Thais P Banzato
- Instituto de Biologia , Universidade Estadual Campinas , Campinas , SP , Brazil
- Centro de Pesquisas Químicas , Biológicas e Agrícolas , Universidade Estadual de Campinas , Campinas , SP , Brazil
| | - Paula A Monteiro
- Instituto de Biologia , Universidade Estadual Campinas , Campinas , SP , Brazil
- Centro de Pesquisas Químicas , Biológicas e Agrícolas , Universidade Estadual de Campinas , Campinas , SP , Brazil
| | - Ronaldo A Pilli
- Instituto de Química , Universidade Estadual de Campinas , Campinas , SP , Brazil
| | - João Ernesto de Carvalho
- Instituto de Biologia , Universidade Estadual Campinas , Campinas , SP , Brazil
- Centro de Pesquisas Químicas , Biológicas e Agrícolas , Universidade Estadual de Campinas , Campinas , SP , Brazil
| | - Dennis Russowsky
- Instituto de Química , Universidade Federal do Rio Grande do Sul , Porto Alegre , RS , Brazil .
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Tsai CC, Li YS, Lin PP. Inonotus obliquus extract induces apoptosis in the human colorectal carcinoma’s HCT-116 cell line. Biomed Pharmacother 2017; 96:1119-1126. [DOI: 10.1016/j.biopha.2017.11.111] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Revised: 11/19/2017] [Accepted: 11/20/2017] [Indexed: 01/01/2023] Open
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Ferrazzi P, Vercelli M, Chakir A, Romane A, Mattana M, Consonni R. Pollination effects on antioxidant content of Perilla frutescens seeds analysed by NMR spectroscopy. Nat Prod Res 2017; 31:2705-2711. [PMID: 28278651 DOI: 10.1080/14786419.2017.1292267] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Accepted: 01/30/2017] [Indexed: 10/20/2022]
Abstract
The effects of Perilla frutescens pollination on the content of seed antioxidants were analysed by agronomical and pollination trials, comparing seeds produced from bagged plants in 2013 (A) to prevent access to pollinating insects, and seeds from open-pollinated plants in 2013 (B) and 2015 (C). The seeds of open-pollinated plants were significantly more numerous and heavier than those of self-pollinated plants. 1H NMR seed analysis showed a higher presence of phenolic compounds in open-pollinated seeds, mainly rosmarinic acid and flavonoids, apigenin and luteolin. Flavonoids were present in the glucosylated form in seeds (A) and (C), and in the aglycone form in seeds from (B) plants. Saturated and unsaturated fatty acids (palmitic, linoleic and linolenic) were more abundant in seeds from self-pollinated flowers. Pollination performed almost exclusively by the honeybee notably increased the antioxidant content in perilla seeds and gave rise to a reduction in the fatty acid content.
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Affiliation(s)
- Paola Ferrazzi
- a Department of Agricultural, Forestry and Food Science , University of Turin , Grugliasco , Italy
| | - Monica Vercelli
- a Department of Agricultural, Forestry and Food Science , University of Turin , Grugliasco , Italy
| | - Amina Chakir
- b Faculty of Sciences Semlalia, Department of Applied Organic Chemistry , University Cadi Ayyad , Marrakech , Morocco
| | - Abderrahmane Romane
- b Faculty of Sciences Semlalia, Department of Applied Organic Chemistry , University Cadi Ayyad , Marrakech , Morocco
| | - Monica Mattana
- c Institute of agricultural biology and biotechnology (IBBA) , Milano , Italy
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Yousefi K, Hamedeyazdan S, Hodaei D, Lotfipour F, Baradaran B, Orangi M, Fathiazad F. An in vitro ethnopharmacological study on Prangos ferulacea: a wound healing agent. ACTA ACUST UNITED AC 2017; 7:75-82. [PMID: 28752071 PMCID: PMC5524988 DOI: 10.15171/bi.2017.10] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Revised: 02/18/2017] [Accepted: 03/06/2017] [Indexed: 12/03/2022]
Abstract
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Introduction: Traditionally Prangos ferulacea root is being used as an effective wound healing agent especially for pus-filled wounds both in human and stocks in the western north of Iran. Regarding the subject we decided to study P. ferulacea roots essential oil (PFE) for its antimicrobial and wound healing activities.
Methods: The in vitro wound healing activity of PFE was evaluated in the mouse fibroblast cell line L929 using MTT assay of cell viability and cytotoxicity indices. Scratch assay as an in vitro model of wound healing assay was also conducted in this study. Moreover, the type I collagen content was used as an indicator of progress in wound healing process using Sircol collagen assay. Besides, PFE was subjected to GC/MS to identify the chemical constituents, and antimicrobical property was also evaluated against S. aureus, S. epidermidis, E. coli, P. aeruginosa,S. paratyphi and C. albicans using agar dilution method.
Results: GC/MS analysis showed that the monoterpene hydrocarbones dominated in PFE, amounting to a total percentage of 95.1% with the major constituents: β-Phellandrene (32.1%), m-Tolualdehyde (26.2%), and δ-3-carene (25.8%). PFE inhibited the growth of S. aureus and P. aeruginusa with the MIC value of 20 µg/mL. In addition, at the second day of treatment, PFE at concentrations of 4 and 16 µg/mL significantly (P<0.001) enhanced the migration rate of L929 cells by 87.05±2.4 and 63.5±0.08 %, respectively. Moreover, the collagen production by L929 cells was increased greatly (P<0.001).
Conclusion: It is proposed that the excellent antimicrobial activity along with the significant increase of migration rate and collagen production by fibroblast cells might be associated with the high content and synergistic effect of the monoterpens, corroborating the traditional usage of this plant as a wound healing agent.
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Affiliation(s)
- Keyvan Yousefi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sanaz Hamedeyazdan
- Department of Pharmacognosy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Darya Hodaei
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Farzaneh Lotfipour
- Department of Drug and Food Control, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mona Orangi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Fathiazad
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Pharmacognosy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
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25
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Cho KS, Lim YR, Lee K, Lee J, Lee JH, Lee IS. Terpenes from Forests and Human Health. Toxicol Res 2017; 33:97-106. [PMID: 28443180 PMCID: PMC5402865 DOI: 10.5487/tr.2017.33.2.097] [Citation(s) in RCA: 97] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Revised: 02/14/2017] [Accepted: 02/16/2017] [Indexed: 12/18/2022] Open
Abstract
Forest bathing has beneficial effects on human health via showering of forest aerosols as well as physical relaxation. Terpenes that consist of multiple isoprene units are the largest class of organic compounds produced by various plants, and one of the major components of forest aerosols. Traditionally, terpene-containing plant oil has been used to treat various diseases without knowing the exact functions or the mechanisms of action of the individual bioactive compounds. This review categorizes various terpenes easily obtained from forests according to their anti-inflammatory, anti-tumorigenic, or neuroprotective activities. Moreover, potential action mechanisms of the individual terpenes and their effects on such processes, which are described in various in vivo and in vitro systems, are discussed. In conclusion, the studies that show the biological effectiveness of terpenes support the benefits of forest bathing and propose a potential use of terpenes as chemotherapeutic agents for treating various human diseases.
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Affiliation(s)
- Kyoung Sang Cho
- Department of Biological Sciences, Konkuk University, Seoul, Korea.,Research Center for Coupled Human and Natural Systems for Ecowelfare, Konkuk University, Seoul, Korea
| | - Young-Ran Lim
- Department of Biological Sciences, Konkuk University, Seoul, Korea
| | - Kyungho Lee
- Department of Biological Sciences, Konkuk University, Seoul, Korea.,Research Center for Coupled Human and Natural Systems for Ecowelfare, Konkuk University, Seoul, Korea
| | - Jaeseok Lee
- Department of Biological Sciences, Konkuk University, Seoul, Korea.,Research Center for Coupled Human and Natural Systems for Ecowelfare, Konkuk University, Seoul, Korea
| | - Jang Ho Lee
- Department of Biological Sciences, Konkuk University, Seoul, Korea
| | - Im-Soon Lee
- Department of Biological Sciences, Konkuk University, Seoul, Korea.,Research Center for Coupled Human and Natural Systems for Ecowelfare, Konkuk University, Seoul, Korea
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26
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Weber L, Al-Refae K, Ebbert J, Jägers P, Altmüller J, Becker C, Hahn S, Gisselmann G, Hatt H. Activation of odorant receptor in colorectal cancer cells leads to inhibition of cell proliferation and apoptosis. PLoS One 2017; 12:e0172491. [PMID: 28273117 PMCID: PMC5342199 DOI: 10.1371/journal.pone.0172491] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Accepted: 02/06/2017] [Indexed: 11/19/2022] Open
Abstract
The analysis and functional characterization of ectopically expressed human olfactory receptors (ORs) is becoming increasingly important, as many ORs have been identified in several healthy and cancerous tissues. OR activation has been demonstrated to have influence on cancer cell growth and progression. Here, ORs were identified using RNA-Seq analyses and RT-PCR. We demonstrated the OR protein localization in HCT116 cells using immunocytochemistry (IHC). In order to analyze the physiological role of OR51B4, we deorphanized the receptor by the use of CRE-Luciferase assays, conducted calcium imaging experiments as well as scratch- and proliferation assays. Furthermore, western blot analyses revealed the involvement of different protein kinases in the ligand-dependent signaling pathway. Receptor knockdown via shRNA was used to analyze the involvement of OR51B4. We identified OR51B4, which is highly expressed in the colon cancer cell line HCT116 and in native human colon cancer tissues. We deorphanized the receptor and identified Troenan as an effective ligand. Troenan stimulation of HCT116 cells has anti-proliferative, anti-migratory and pro-apoptotic effects, mediated by changes in the intracellular calcium level upon PLC activation. These effects cause changes in the phosphorylation levels of p38, mTor and Akt kinases. Knockdown of the receptor via shRNA confirmed the involvement of OR51B4. This study emphasizes the importance of ectopically expressed ORs in the therapy for several diseases. The findings provide the basis for alternative treatments of colorectal cancer.
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Affiliation(s)
- Lea Weber
- Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany
- * E-mail:
| | - Klaudia Al-Refae
- Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany
- Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, University Hospital, Essen, Germany
| | - Juliane Ebbert
- Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany
| | - Peter Jägers
- Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany
| | - Janine Altmüller
- Cologne Center for Genomics, University of Cologne, Cologne, Germany
| | - Christian Becker
- Cologne Center for Genomics, University of Cologne, Cologne, Germany
| | - Stephan Hahn
- Department of Molecular Gastrointestinal Oncology, Ruhr-University Bochum, Bochum, Germany
| | - Günter Gisselmann
- Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany
| | - Hanns Hatt
- Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany
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27
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Tappin MRR, Knopp FM, Cardoso IC, Santos RT, Drummond BS, Siani AC, Bon EPS, Ferrara MA. Synthesis of the Prospective Anticancer Molecule Perillic Acid from Orange Essential Oil by the Yeast <i>Yarrowia lipolytica</i>. ACTA ACUST UNITED AC 2017. [DOI: 10.4236/gsc.2017.72013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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28
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Terpenoids as anti-colon cancer agents - A comprehensive review on its mechanistic perspectives. Eur J Pharmacol 2016; 795:169-178. [PMID: 27940056 DOI: 10.1016/j.ejphar.2016.12.008] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2016] [Revised: 12/05/2016] [Accepted: 12/05/2016] [Indexed: 02/06/2023]
Abstract
Multistep model of colon carcinogenesis has provided the framework to advance our understanding of the molecular basis of colon cancer. This multistage process of carcinogenesis takes a long period to transform from a normal epithelial cell to invasive carcinoma. Thus, it provides enough time to intervene the process of carcinogenesis especially through dietary modification. In spite of the in-depth understanding of the colon cancer etiology and pathophysiology and its association with diet, colon cancer remains a major cause of cancer mortality worldwide. Phytochemicals and their derivatives are gaining attention in cancer prevention and treatment strategies because of cancer chemotherapy associated adverse effects. Being the largest group of phytochemicals traditionally used for medicinal purpose in India and China, terpenoids are recently being explored as anticancer agents. Anticancer properties of terpenoids are associated with various mechanisms like counteraction of oxidative stress, potentiating endogenous antioxidants, improving detoxification potential, disrupting cell survival pathways and inducing apoptosis. This review gives a comprehensive idea of naturally occurring terpenoids as useful agents for the prevention of colon cancer with reference to their classes, sources and molecular targets. Based on the explored molecular targets further research in colon cancer chemoprevention is warranted.
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29
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Lee S, Park YR, Kim SH, Park EJ, Kang MJ, So I, Chun JN, Jeon JH. Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med 2016; 5:2899-2908. [PMID: 27683099 PMCID: PMC5083744 DOI: 10.1002/cam4.864] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2016] [Revised: 07/04/2016] [Accepted: 07/19/2016] [Indexed: 12/23/2022] Open
Abstract
Geraniol, an acyclic dietary monoterpene, has been found to suppress cancer survival and growth. However, the molecular mechanism underlying the antitumor action of geraniol has not been investigated at the genome-wide level. In this study, we analyzed the microarray data obtained from geraniol-treated prostate cancer cells. Geraniol potently altered a gene expression profile and primarily down-regulated cell cycle-related gene signatures, compared to linalool, another structurally similar monoterpene that induces no apparent phenotypic changes. Master regulator analysis using the prostate cancer-specific regulatory interactome identified that the transcription factor E2F8 as a specific target molecule regulates geraniol-specific cell cycle signatures. Subsequent experiments confirmed that geraniol down-regulated E2F8 expression and the knockdown of E2F8 was sufficient to suppress cell growth by inducing G2 /M arrest. Epidemiological analysis showed that E2F8 is up-regulated in metastatic prostate cancer and associated with poor prognosis. These results indicate that E2F8 is a crucial transcription regulator controlling cell cycle and survival in prostate cancer cells. Therefore, our study provides insight into the role of E2F8 in prostate cancer biology and therapeutics.
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Affiliation(s)
- Sanghoon Lee
- Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah, 84112 5650
| | - Yu Rang Park
- Office of Clinical Research Information, Asan Medical Center, Seoul, 05535, Korea
| | - Su-Hwa Kim
- Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Korea
| | - Eun-Jung Park
- Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Korea
| | - Min Ji Kang
- Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, 05535, Korea
| | - Insuk So
- Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Korea.,Institute of Human-Environment Interface Biology, Seoul National University, Seoul, 03080, Korea
| | - Jung Nyeo Chun
- Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Korea. .,Institute of Human-Environment Interface Biology, Seoul National University, Seoul, 03080, Korea.
| | - Ju-Hong Jeon
- Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Korea. .,Institute of Human-Environment Interface Biology, Seoul National University, Seoul, 03080, Korea.
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30
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Cho M, So I, Chun JN, Jeon JH. The antitumor effects of geraniol: Modulation of cancer hallmark pathways (Review). Int J Oncol 2016; 48:1772-82. [PMID: 26983575 PMCID: PMC4809657 DOI: 10.3892/ijo.2016.3427] [Citation(s) in RCA: 97] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2015] [Accepted: 02/18/2016] [Indexed: 12/30/2022] Open
Abstract
Geraniol is a dietary monoterpene alcohol that is found in the essential oils of aromatic plants. To date, experimental evidence supports the therapeutic or preventive effects of geraniol on different types of cancer, such as breast, lung, colon, prostate, pancreatic, and hepatic cancer, and has revealed the mechanistic basis for its pharmacological actions. In addition, geraniol sensitizes tumor cells to commonly used chemotherapy agents. Geraniol controls a variety of signaling molecules and pathways that represent tumor hallmarks; these actions of geraniol constrain the ability of tumor cells to acquire adaptive resistance against anticancer drugs. In the present review, we emphasize that geraniol is a promising compound or chemical moiety for the development of a safe and effective multi-targeted anticancer agent. We summarize the current knowledge of the effects of geraniol on target molecules and pathways in cancer cells. Our review provides novel insight into the challenges and perspectives with regard to geraniol research and to its application in future clinical investigation.
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Affiliation(s)
- Minsoo Cho
- Undergraduate Research Program, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Insuk So
- Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Jung Nyeo Chun
- Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Ju-Hong Jeon
- Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
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31
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Booupathy LK, Venkatachalam S, Natarajan N, Thamaraiselvan R, Arumugam M, Maruthaiveeran Periyasamy B. Chemopreventive effect of myrtenal on bacterial enzyme activity and the development of 1,2-dimethyl hydrazine-induced aberrant crypt foci in Wistar Rats. J Food Drug Anal 2016; 24:206-213. [PMID: 28911405 PMCID: PMC9345433 DOI: 10.1016/j.jfda.2015.07.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2015] [Revised: 07/05/2015] [Accepted: 07/16/2015] [Indexed: 01/04/2023] Open
Abstract
Colon cancer remains as a serious health problem around the world despite advances in diagnosis and treatment. Dietary fibers are considered to reduce the risk of colon cancer as they are converted to short chain fatty acids by the presence of anaerobic bacteria in the intestine, but imbalanced diet and high fat consumption may promote tumor formation at different sites, including the large bowel via increased bacterial enzymes activity. The present study was conducted to characterize the inhibitory action of myrtenal on bacterial enzymes and aberrant crypt foci (ACF). Experimental colon carcinogenesis induced by 1,2-dimethylhydrazine is histologically, morphologically, and anatomically similar to human colonic epithelial neoplasm. Discrete microscopic mucosal lesions such as ACF and malignant tumors function as important biomarkers in the diagnosis of colon cancer. Methylene blue staining was carried out to visualize the impact of 1,2-dimethylhydrazine and myrtenal. Myrtenal-treated animals showed decreased levels of bacterial enzymes such as β-glucuronidase, β-glucosidase, and mucinase. Characteristic changes in the colon were noticed by inhibiting ACF formation in the colon. In conclusion, treatment with myrtenal provided altered pathophysiological condition in colon cancer-bearing animals with evidence of decreased crypt multiplicity and tumor progression.
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32
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Mendanha SA, Alonso A. Effects of terpenes on fluidity and lipid extraction in phospholipid membranes. Biophys Chem 2015; 198:45-54. [PMID: 25687600 DOI: 10.1016/j.bpc.2015.02.001] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2014] [Revised: 01/29/2015] [Accepted: 02/01/2015] [Indexed: 12/16/2022]
Abstract
Electron paramagnetic resonance (EPR) spectroscopy was used in a detailed study of the interactions of several terpenes with DPPC membranes. EPR spectra of a spin-label lipid allowed the identification of two well-resolved spectral components at temperatures below and above the main phase transition of the lipid bilayer. Terpenes caused only slight mobility increases in each of these spectral components; however, they substantially increased the population of the more mobile component. In addition, the terpenes reduced the temperature of the main phase transition by more than 8 °C and caused the extraction of the spin-labeled lipid. Nerolidol, which had the highest octanol-water partition coefficient, generated the highest amount of spin label extraction. Acting as spacers, terpenes should cause major reorganization in cell membranes, leading to an increase in the overall molecular dynamics of the membrane. At higher concentrations, terpenes may cause lipid extraction and thus leakage of the cytoplasmic content.
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Affiliation(s)
| | - Antonio Alonso
- Instituto de Física, Universidade Federal de Goiás, Goiânia, GO, Brazil.
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33
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Kumari S, Pundhir S, Priya P, Jeena G, Punetha A, Chawla K, Firdos Jafaree Z, Mondal S, Yadav G. EssOilDB: a database of essential oils reflecting terpene composition and variability in the plant kingdom. DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION 2014; 2014:bau120. [PMID: 25534749 PMCID: PMC4273207 DOI: 10.1093/database/bau120] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Plant essential oils are complex mixtures of volatile organic compounds, which play indispensable roles in the environment, for the plant itself, as well as for humans. The potential biological information stored in essential oil composition data can provide an insight into the silent language of plants, and the roles of these chemical emissions in defense, communication and pollinator attraction. In order to decipher volatile profile patterns from a global perspective, we have developed the ESSential OIL DataBase (EssOilDB), a continually updated, freely available electronic database designed to provide knowledge resource for plant essential oils, that enables one to address a multitude of queries on volatile profiles of native, invasive, normal or stressed plants, across taxonomic clades, geographical locations and several other biotic and abiotic influences. To our knowledge, EssOilDB is the only database in the public domain providing an opportunity for context based scientific research on volatile patterns in plants. EssOilDB presently contains 123 041 essential oil records spanning a century of published reports on volatile profiles, with data from 92 plant taxonomic families, spread across diverse geographical locations all over the globe. We hope that this huge repository of VOCs will facilitate unraveling of the true significance of volatiles in plants, along with creating potential avenues for industrial applications of essential oils. We also illustrate the use of this database in terpene biology and show how EssOilDB can be used to complement data from computational genomics to gain insights into the diversity and variability of terpenoids in the plant kingdom. EssOilDB would serve as a valuable information resource, for students and researchers in plant biology, in the design and discovery of new odor profiles, as well as for entrepreneurs—the potential for generating consumer specific scents being one of the most attractive and interesting topics in the cosmetic industry. Database URL: http://nipgr.res.in/Essoildb/
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Affiliation(s)
- Sangita Kumari
- Computational Biology Laboratory, National Institute of Plant Genome Research (NIPGR), New Delhi 110067 India
| | - Sachin Pundhir
- Computational Biology Laboratory, National Institute of Plant Genome Research (NIPGR), New Delhi 110067 India
| | - Piyush Priya
- Computational Biology Laboratory, National Institute of Plant Genome Research (NIPGR), New Delhi 110067 India
| | - Ganga Jeena
- Computational Biology Laboratory, National Institute of Plant Genome Research (NIPGR), New Delhi 110067 India
| | - Ankita Punetha
- Computational Biology Laboratory, National Institute of Plant Genome Research (NIPGR), New Delhi 110067 India
| | - Konika Chawla
- Computational Biology Laboratory, National Institute of Plant Genome Research (NIPGR), New Delhi 110067 India
| | - Zohra Firdos Jafaree
- Computational Biology Laboratory, National Institute of Plant Genome Research (NIPGR), New Delhi 110067 India
| | - Subhasish Mondal
- Computational Biology Laboratory, National Institute of Plant Genome Research (NIPGR), New Delhi 110067 India
| | - Gitanjali Yadav
- Computational Biology Laboratory, National Institute of Plant Genome Research (NIPGR), New Delhi 110067 India
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34
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Maßberg D, Simon A, Häussinger D, Keitel V, Gisselmann G, Conrad H, Hatt H. Monoterpene (-)-citronellal affects hepatocarcinoma cell signaling via an olfactory receptor. Arch Biochem Biophys 2014; 566:100-9. [PMID: 25513961 DOI: 10.1016/j.abb.2014.12.004] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2014] [Revised: 12/03/2014] [Accepted: 12/04/2014] [Indexed: 12/15/2022]
Abstract
Terpenes are the major constituents of essential oils in plants. In recent years, terpenes have become of clinical relevance due to their ability to suppress cancer development. Their effect on cellular proliferation has made them promising agents in the prevention or treatment of many types of cancer. In the present study, a subset of different monoterpenes was investigated for their molecular effects on the hepatocellular carcinoma cell line Huh7. Using fluorometric calcium imaging, acyclic monoterpene (-)-citronellal was found to induce transient Ca(2+) signals in Huh7 cells by activating a cAMP-dependent signaling pathway. Moreover, we detected the (-)-citronellal-activated human olfactory receptor OR1A2 at the mRNA and protein levels and demonstrated its potential involvement in (-)-citronellal-induced calcium signaling in Huh7 cells. Furthermore, activation of OR1A2 results in phosphorylation of p38 MAPK and reduced cell proliferation, indicating an effect on hepatocellular carcinoma progression. Here, we provide for the first time data on the molecular mechanism evoked by (-)-citronellal in human hepatocellular carcinoma cells. The identified olfactory receptor could serve as a potential therapeutic target for cancer diagnosis and treatment.
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Affiliation(s)
- Désirée Maßberg
- Department of Cell Physiology, Ruhr-University Bochum, 44801 Bochum, Germany.
| | - Annika Simon
- Department of Cell Physiology, Ruhr-University Bochum, 44801 Bochum, Germany.
| | - Dieter Häussinger
- Clinic of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.
| | - Verena Keitel
- Clinic of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.
| | - Günter Gisselmann
- Department of Cell Physiology, Ruhr-University Bochum, 44801 Bochum, Germany.
| | - Heike Conrad
- Department of Cell Physiology, Ruhr-University Bochum, 44801 Bochum, Germany.
| | - Hanns Hatt
- Department of Cell Physiology, Ruhr-University Bochum, 44801 Bochum, Germany.
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35
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Afshordel S, Kern B, Clasohm J, König H, Priester M, Weissenberger J, Kögel D, Eckert GP. Lovastatin and perillyl alcohol inhibit glioma cell invasion, migration, and proliferation--impact of Ras-/Rho-prenylation. Pharmacol Res 2014; 91:69-77. [PMID: 25497898 DOI: 10.1016/j.phrs.2014.11.006] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2014] [Revised: 11/27/2014] [Accepted: 11/29/2014] [Indexed: 11/19/2022]
Abstract
Alterations in small GTPase mediated signal transduction pathways have emerged as a central step in the molecular pathogenesis of glioblastoma (GBM), the most common malignant brain tumor in adults. Farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP) are derived from mevalonate, whose production is catalyzed by 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. Prenylation by FPP and GGPP is required for membrane insertion and oncogenic function of Ras- and Rho-proteins, within the stimulation of the Ras-Raf-MEK-ERK pathway. A straightforward prediction from HMG-CoA reductase inhibitor studies is that statins decrease FPP and GGPP levels and diminish ERK signaling ensuring less proliferation and migration of cancer cells. Perillyl alcohol (POH), a naturally occurring monoterpene inhibits prenyltransferases and is able to inhibit cancer cell growth, but the underlying mechanism is still unclear. We here report that lovastatin (LOV) and POH impair the regulation of the mevalonate- and the Ras-Raf-MEK-ERK pathway in U87 and U343 glioblastoma cells. Both compounds affected the post-translational modification of H-Ras and Rac1. While LOV diminished the substrates of the transferase reaction that catalyze prenylation, POH inhibited the enzymes itself. Our data highlight the impact of isoprenoids for post-translational modification of small GTPases promoting proliferation, migration and invasion capabilities in glioma cells.
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Affiliation(s)
- Sarah Afshordel
- Department of Pharmacology, Goethe-University, Frankfurt, Germany
| | - Beatrice Kern
- Department of Pharmacology, Goethe-University, Frankfurt, Germany
| | - Jasmin Clasohm
- Department of Pharmacology, Goethe-University, Frankfurt, Germany
| | - Hildegard König
- Division of Experimental Neurosurgery, University Clinics of Frankfurt, Germany
| | - Maike Priester
- Division of Experimental Neurosurgery, University Clinics of Frankfurt, Germany
| | - Jakob Weissenberger
- Division of Experimental Neurosurgery, University Clinics of Frankfurt, Germany
| | - Donat Kögel
- Division of Experimental Neurosurgery, University Clinics of Frankfurt, Germany
| | - Gunter P Eckert
- Department of Pharmacology, Goethe-University, Frankfurt, Germany.
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36
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Camargos HS, Moreira RA, Mendanha SA, Fernandes KS, Dorta ML, Alonso A. Terpenes increase the lipid dynamics in the Leishmania plasma membrane at concentrations similar to their IC50 values. PLoS One 2014; 9:e104429. [PMID: 25101672 PMCID: PMC4125203 DOI: 10.1371/journal.pone.0104429] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2014] [Accepted: 07/11/2014] [Indexed: 02/06/2023] Open
Abstract
Although many terpenes have shown antitumor, antibacterial, antifungal, and antiparasitic activity, the mechanism of action is not well established. Electron paramagnetic resonance (EPR) spectroscopy of the spin-labeled 5-doxyl stearic acid revealed remarkable fluidity increases in the plasma membrane of terpene-treated Leishmania amazonensis promastigotes. For an antiproliferative activity assay using 5×106 parasites/mL, the sesquiterpene nerolidol and the monoterpenes (+)-limonene, α-terpineol and 1,8-cineole inhibited the growth of the parasites with IC50 values of 0.008, 0.549, 0.678 and 4.697 mM, respectively. The IC50 values of these terpenes increased as the parasite concentration used in the cytotoxicity assay increased, and this behavior was examined using a theoretical treatment of the experimental data. Cytotoxicity tests with the same parasite concentration as in the EPR experiments revealed a correlation between the IC50 values of the terpenes and the concentrations at which they altered the membrane fluidity. In addition, the terpenes induced small amounts of cell lysis (4–9%) at their respective IC50 values. For assays with high cell concentrations (2×109 parasites/mL), the incorporation of terpene into the cell membrane was very fast, and the IC50 values observed for 24 h and 5 min-incubation periods were not significantly different. Taken together, these results suggest that terpene cytotoxicity is associated with the attack on the plasma membrane of the parasite. The in vitro cytotoxicity of nerolidol was similar to that of miltefosine, and nerolidol has high hydrophobicity; thus, nerolidol might be used in drug delivery systems, such as lipid nanoparticles to treat leishmaniasis.
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Affiliation(s)
- Heverton Silva Camargos
- Instituto de Física, Universidade Federal de Goiás, Goiânia, GO, Brazil
- Engenharia Elétrica, Fundação Universidade Federal do Tocantins, Palmas, TO, Brasil
| | | | | | | | - Miriam Leandro Dorta
- Instituto de Patologia Tropical e Saúde Publica, Departamento de Imunologia e Patologia Geral, Universidade Federal de Goiás, Goiânia, GO, Brazil
| | - Antonio Alonso
- Instituto de Física, Universidade Federal de Goiás, Goiânia, GO, Brazil
- * E-mail:
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37
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Essential oils and their constituents as anticancer agents: a mechanistic view. BIOMED RESEARCH INTERNATIONAL 2014; 2014:154106. [PMID: 25003106 PMCID: PMC4070586 DOI: 10.1155/2014/154106] [Citation(s) in RCA: 143] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/26/2014] [Accepted: 04/11/2014] [Indexed: 12/31/2022]
Abstract
Exploring natural plant products as an option to find new chemical entities as anticancer agents is one of the fastest growing areas of research. Recently, in the last decade, essential oils (EOs) have been under study for their use in cancer therapy and the present review is an attempt to collect and document the available studies indicating EOs and their constituents as anticancer agents. This review enlists nearly 130 studies of EOs from various plant species and their constituents that have been studied so far for their anticancer potential and these studies have been classified as in vitro and in vivo studies for EOs and their constituents. This review also highlights in-depth various mechanisms of action of different EOs and their constituents reported in the treatment strategies for different types of cancer. The current review indicates that EOs and their constituents act by multiple pathways and mechanisms involving apoptosis, cell cycle arrest, antimetastatic and antiangiogenic, increased levels of reactive oxygen and nitrogen species (ROS/RNS), DNA repair modulation, and others to demonstrate their antiproliferative activity in the cancer cell. The effect of EOs and their constituents on tumour suppressor proteins (p53 and Akt), transcription factors (NF- κB and AP-1), MAPK-pathway, and detoxification enzymes like SOD, catalase, glutathione peroxidase, and glutathione reductase has also been discussed.
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A review on bioactivities of perilla: progress in research on the functions of perilla as medicine and food. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:925342. [PMID: 24319488 PMCID: PMC3844277 DOI: 10.1155/2013/925342] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/12/2013] [Accepted: 09/24/2013] [Indexed: 11/17/2022]
Abstract
Perilla is a useful pharmaceutical and food product and is empirically consumed by humans. However, its properties have not been evaluated extensively. In this review, we summarize the progress made in research, focusing on the bioactivities of perilla. There are many in vitro and animal studies on the cytostatic activity and antiallergic effects, respectively, of perilla and its constituents. However, its influence on humans remains unclear. Hence, investigating and clarifying the physiological effects of perilla and its constituents on humans are imperative in the future to adhere to the ideals of evidence-based medicine.
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Mendanha SA, Moura SS, Anjos JLV, Valadares MC, Alonso A. Toxicity of terpenes on fibroblast cells compared to their hemolytic potential and increase in erythrocyte membrane fluidity. Toxicol In Vitro 2012; 27:323-9. [PMID: 22944593 DOI: 10.1016/j.tiv.2012.08.022] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2012] [Revised: 07/28/2012] [Accepted: 08/16/2012] [Indexed: 01/11/2023]
Abstract
Terpenes are considered potent skin permeation enhancers with low toxicity. Electron paramagnetic resonance (EPR) spectroscopy of the spin label 5-doxyl stearic acid (5-DSA) was used to monitor the effect of sesquiterpene nerolidol and various monoterpenes on membrane fluidity in erythrocyte and fibroblast cells. In addition, the hemolytic levels and cytotoxic effects on cultured fibroblast cells were also measured to investigate possible relationships between the cellular irritation potentials of terpenes and the ability to modify membrane fluidity. All terpenes increased cell membrane fluidity with no significant differences between the monoterpenes, but the effect of sesquiterpene was significantly greater than that of the monoterpenes. The IC(50) values for the terpenes in the cytotoxicity assay indicated that 1,8-cineole showed lower cytotoxicity and α-terpineol and nerolidol showed higher cytotoxicity. The correlation between the hemolytic effect and the IC(50) values for fibroblast viability was low (R=0.61); however, in both tests, nerolidol was among the most aggressive of terpenes and 1,8-cineole was among the least aggressive. Obtaining information concerning the toxicity and potency of terpenes could aid in the design of topical formulations optimized to facilitate drug absorption for the treatment of many skin diseases.
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Growth inhibition of human gynecologic and colon cancer cells by Phyllanthus watsonii through apoptosis induction. PLoS One 2012; 7:e34793. [PMID: 22536331 PMCID: PMC3335034 DOI: 10.1371/journal.pone.0034793] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2011] [Accepted: 03/08/2012] [Indexed: 12/18/2022] Open
Abstract
Phyllanthus watsonii Airy Shaw is an endemic plant found in Peninsular Malaysia. Although there are numerous reports on the anti cancer properties of other Phyllanthus species, published information on the cytotoxicity of P. watsonii are very limited. The present study was carried out with bioassay-guided fractionation approach to evaluate the cytotoxicity and apoptosis induction capability of the P. watsonii extracts and fractions on human gynecologic (SKOV-3 and Ca Ski) and colon (HT-29) cancer cells. P. watsonii extracts exhibited strong cytotoxicity on all the cancer cells studied with IC(50) values of ≤ 20.0 µg/mL. Hexane extract of P. watsonii was further subjected to bioassay-guided fractionation and yielded 10 fractions (PW-1→PW-10). PW-4→PW-8 portrayed stronger cytotoxic activity and was further subjected to bioassay-guided fractionation and resulted with 8 sub-fractions (PPWH-1→PPWH-8). PPWH-7 possessed greatest cytotoxicity (IC(50) values ranged from 0.66-0.83 µg/mL) and was selective on the cancer cells studied. LC-MS/MS analysis of PPWH-7 revealed the presence of ellagic acid, geranic acid, glochidone, betulin, phyllanthin and sterol glucoside. Marked morphological changes, ladder-like appearance of DNA and increment in caspase-3 activity indicating apoptosis were clearly observed in both human gynecologic and colon cancer cells treated with P. watsonii especially with PPWH-7. The study also indicated that P. watsonii extracts arrested cell cycle at different growth phases in SKOV-3, Ca Ski and HT-29 cells. Cytotoxic and apoptotic potential of the endemic P. watsonii was investigated for the first time by bioassay-guided approach. These results demonstrated that P. watsonii selectively inhibits the growth of SKOV-3, Ca Ski and HT-29 cells through apoptosis induction and cell cycle modulation. Hence, P. watsonii has the potential to be further exploited for the discovery and development of new anti cancer drugs.
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Chidambara Murthy KN, Jayaprakasha GK, Mantur SM, Patil BS. Citrus Monoterpenes: Potential Source of Phytochemicals for Cancer Prevention. ACS SYMPOSIUM SERIES 2012. [DOI: 10.1021/bk-2012-1093.ch031] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Affiliation(s)
- Kotamballi N. Chidambara Murthy
- Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, Texas, U.S.A
- Hi-Tech Horticulture Unit, University of Agricultural Sciences, Dharwad, India
| | - G. K. Jayaprakasha
- Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, Texas, U.S.A
- Hi-Tech Horticulture Unit, University of Agricultural Sciences, Dharwad, India
| | - Shivappa M. Mantur
- Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, Texas, U.S.A
- Hi-Tech Horticulture Unit, University of Agricultural Sciences, Dharwad, India
| | - Bhimanagouda S. Patil
- Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, Texas, U.S.A
- Hi-Tech Horticulture Unit, University of Agricultural Sciences, Dharwad, India
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Abstract
S-(-)-Perillyl alcohol ( p-mentha-1, 8-diene-7-ol) (1) (500 mg) was converted by Fusarium heterosporium ATCC 15625 over 10 days at 25°C to a new metabolite, 1,2-dihydroxyperillyl alcohol ( p-mentha-8-en-1,2,7-triol) (3) in a yield of 13% (70 mg). The structure of 3 was established by IR and NMR spectroscopic, specific rotation, and mass spectral studies.
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Affiliation(s)
- Ismail Kiran
- Department of Chemistry, Faculty of Arts and Sciences, Eskisehir Osmangazi University, 26480, Eskişehir, Turkey
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Kuttan G, Pratheeshkumar P, Manu KA, Kuttan R. Inhibition of tumor progression by naturally occurring terpenoids. PHARMACEUTICAL BIOLOGY 2011; 49:995-1007. [PMID: 21936626 DOI: 10.3109/13880209.2011.559476] [Citation(s) in RCA: 86] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
CONTEXT Cancer is a major public health problem in India and many other parts of the world. Its two main characteristics are uncontrolled cell growth and metastasis. Natural products represent a rich source of compounds that have found many applications in various fields of medicines and therapy including cancer therapy. Effective ingredients in several plant-derived medicinal extracts are terpenoid compounds and many terpenes have biological activities and are used for the treatment of human diseases. OBJECTIVES This review attempted to collect all available published scientific literature of eight naturally occurring terpenoids and their effect on inhibition of tumor progression. METHODS The present review is about eight potent naturally occurring terpenoids that have been studied for their pharmacological properties in our lab and this review includes 130 references compiled from all major databases. RESULTS Literature survey revealed that triterpenoids, such as glycyrrhizic acid, ursolic acid, oleanolic acid, and nomilin, the diterpene andrographolide, and the monoterpenoids like limonene and perillic acid had shown immunomodulatory and antitumor activities. All of them could induce apoptosis in various cancer cells by activating various proapoptotic signaling cascades. Many of these terpenoids found to inhibit metastatic progression and tumor-induced angiogenesis. The molecular mechanisms that involved in these activities include inhibition of various oncogenic and anti-apoptotic signaling pathways and suppression or nuclear translocation of various transcription factors including nuclear factor kappa B (NF-κB). CONCLUSION The chemopreventive and chemoprotective effects of these compounds point toward their possible role in modern anticancer therapies.
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Affiliation(s)
- Girija Kuttan
- Department of Immunology, Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala, India.
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Evaluation of the antioxidant and antiproliferative potential of bioflavors. Food Chem Toxicol 2011; 49:1610-5. [DOI: 10.1016/j.fct.2011.04.012] [Citation(s) in RCA: 83] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2010] [Revised: 02/25/2011] [Accepted: 04/10/2011] [Indexed: 01/11/2023]
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Rassouli FB, Matin MM, Iranshahi M, Bahrami AR. Investigating the cytotoxic and apoptosis inducing effects of monoterpenoid stylosin in vitro. Fitoterapia 2011; 82:742-9. [PMID: 21459136 DOI: 10.1016/j.fitote.2011.03.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2011] [Revised: 03/13/2011] [Accepted: 03/15/2011] [Indexed: 10/18/2022]
Abstract
The aim of this study was to investigate the cytotoxic and anticancer activities of stylosin, a monoterpene extracted from an edible plant, Ferula ovina, on 5637 and HFF3 cells using MTT and comet assays and DAPI staining. To assess stylosin effects, cells were cultured in the presence of various concentrations of stylosin during three days; the IC(50) of stylosin on cancerous 5637 cells was less than its value on HFF3 normal cells, indicating that it might have anticancer properties. Investigating the mechanism of stylosin action revealed that it quickly induced DNA lesions and increased the number of apoptotic cells.
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Fischer JDSDG, Carvalho PC, Fonseca COD, Liao L, Degrave WM, Carvalho MDGDC, Yates JR, Domont GB. Chemo-resistant protein expression pattern of glioblastoma cells (A172) to perillyl alcohol. J Proteome Res 2011; 10:153-60. [PMID: 20806975 PMCID: PMC3017632 DOI: 10.1021/pr100677g] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Glioblastoma multiform (GBM) is by far the most malignant glioma. We have introduced a new treatment for GBMs that comprises the inhalation of a naturally occurring terpene with chemotherapeutic properties known as perillyl alcohol (POH). Clinical trial results on recurrent GBM patients showed that POH extends the average life by more than eight months, temporarily slows tumor growth, and in some cases even decreases tumor size. After approximately seven months, the tumor continues to grow and leads to a dismal prognosis. To investigate how these tumors become resistant to POH, we generated an A172 human glioblastoma cell culture tolerant to 0.06 mM of POH (A172r). We used Multidimensional Protein Identification Technology (MudPIT) to compare the protein expression profile of A172r cells to the established glioblastoma A172 cell line. Our results include a list of identified proteins unique to either the resistant or the nonresistant cell line. These proteins are related to cellular growth, negative apoptosis regulation, Ras pathway, and other key cellular functions that could be connected to the underlying mechanisms of resistance.
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Affiliation(s)
- Juliana de Saldanha da Gama Fischer
- Center for Technological Development in Health – Oswaldo Cruz Foundation, Ministry of Health, Brazil
- Laboratory for Functional Genomics and Bioinformatics – Oswaldo Cruz Institute, Ministry of Health, Brazil
| | - Paulo Costa Carvalho
- Center for Technological Development in Health – Oswaldo Cruz Foundation, Ministry of Health, Brazil
- Laboratory of Toxinology – Oswaldo Cruz Institute, Ministry of Health, Brazil
| | - Clovis Orlando da Fonseca
- Department of General and Specialized Surgery, Fluminence Federal University, Rio de Janeiro - Brazil
| | - Lujian Liao
- Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA
| | - Wim M Degrave
- Laboratory for Functional Genomics and Bioinformatics – Oswaldo Cruz Institute, Ministry of Health, Brazil
| | | | - John R Yates
- Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA
| | - Gilberto B Domont
- Laboratory for Protein Chemistry / Proteomics Unit Chemistry Institute and the Rio de Janeiro Proteomic Network, Federal University of Rio de Janeiro, Brazil
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Serra AT, Matias AA, Almeida AP, Bronze M, Alves PM, de Sousa HC, Duarte CM. Processing cherries (Prunus avium) using supercritical fluid technology. Part 2. Evaluation of SCF extracts as promising natural chemotherapeutical agents. J Supercrit Fluids 2011. [DOI: 10.1016/j.supflu.2010.06.006] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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The role of Pygopus 2 in rat glioma cell growth. Med Oncol 2010; 28:631-40. [PMID: 20361361 DOI: 10.1007/s12032-010-9488-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2009] [Accepted: 03/10/2010] [Indexed: 12/21/2022]
Abstract
Glioma is a common malignant tumor of the human neural system, and Wnt signaling activation is closely connected with glioma malignancy. Pygopus 2 (Pygo2) was recently discovered as a component of the Wnt signaling pathway regulating β-catenin/Tcf dependent transcription. However, the role of Pygo2 in glioma cells has not yet been defined. In the current study, we investigated the role of Pygo2 in rat glioma C6 cells for the first time. Our results showed that over-expression of Pygo2 promoted cell proliferation as well as enhanced cell cycle progression from G₁ to S phase associated with an increase in the expression of the Wnt target gene cyclin D1. In contrast, knockdown of Pygo2 suppressed cell proliferation with cell cycle block from G₁ to S phase and down-regulation of cyclin D1. In addition, the expression of Pygo2 and cyclin D1 in 67 glioma tissue samples was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunochemistry. The data indicated that tumor grade was significantly associated with over-expression of Pygo2 and cyclin D1. We conclude that Pygo2 is highly expressed in and promotes the growth of glioma cells by an increase in the expression of cyclin D1 to improve G₁/S transition.
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