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Ragab EM, Khamis AA, Mohamed TM, El Gamal DM. Management succinate release through SDHA by G protein-coupled receptor 91 signal, TRAP1, and SIRT3 regulation in lung cancer cells by NAR nanoparticles. J Genet Eng Biotechnol 2025; 23:100464. [PMID: 40074439 PMCID: PMC11870189 DOI: 10.1016/j.jgeb.2025.100464] [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: 08/25/2024] [Revised: 01/24/2025] [Accepted: 01/26/2025] [Indexed: 03/14/2025]
Abstract
BACKGROUND Cancer cells display oxidative metabolic dysregulation to fulfill their bioenergy requirements. Specifically, efforts were made to regulate the metabolite succinate and its negative effects as an inducer for neoplasm invasion and metastasis. METHODS Binding affinity of naringenin (NAR) to mitochondria complex II (CΙΙ) subunits, sirtuin3 (SIRT3), tumor necrosis factor associate protein 1(TRAP1), and succinate receptor (SUCNR1) was studied by molecular docking. NAR nanoparticles (NARNPs) were synthesized and characterized by IR, X-ray, UV, drug release, zeta potential, TEM, and SEM. The IC50 was evaluated in normal mice, normal fibroblast, and A549 cells by using the MTT technique. Moreover, the impact of NAR and NARNPs against 5-FLU on CΙΙ activity, SOD activity, and mitochondrial swelling was assessed. Apoptosis was also assessed using the flow cytometry method. While the expression of relevant genes such as SDHC, D, SIRT-3, TRAP1, SUCNR1, and ERK1/2 genes was determined by using RT-qPCR analysis. Western blot evaluated PI3K, NF-κB against β-actin. RESULTS Theoretically, the binding affinity between NAR & SDHC, D, SIRT-3, TRAP1, and SUCNR1 proteins was stronger. Cytotoxic effects of NAR and NARNPs were evaluated. Also, the activity of SDH C, and D was inhibited more than SDH A, and B activity in the A549 than normal cell lines (NARNPs < NAR < 5-FLU), This was accompanied by downregulation of SDH C, D, TRAP1, SUCNR1, and ERK1/2 genes expression, and upregulation of SIRT-3 gene expression. Additionally, NF-κB and PI3K protein expression declined. On the other hand, there was a significant increase in apoptotic effects with mitochondria enlargement (NARNPs > NAR > 5-FLU) in A549 compared with normal cells. IN CONCLUSION Controlling succinate by SDH parallel with SUCNR1 signal regulation by NARNPs will be a novel understanding mechanism and candidate for therapeutic target in lung cancer.
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Affiliation(s)
- Eman M Ragab
- Biochemistry Division Chemistry Department Faculty of Science Tanta University Tanta Egypt.
| | - Abeer A Khamis
- Biochemistry Division Chemistry Department Faculty of Science Tanta University Tanta Egypt
| | - Tarek M Mohamed
- Biochemistry Division Chemistry Department Faculty of Science Tanta University Tanta Egypt
| | - Doaa M El Gamal
- Biochemistry Division Chemistry Department Faculty of Science Tanta University Tanta Egypt
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Ragab EM, Khamis AA, Gamal DME, Mohamed TM. Comprehensive overview of how to fade into succinate dehydrogenase dysregulation in cancer cells by naringenin-loaded chitosan nanoparticles. GENES & NUTRITION 2024; 19:10. [PMID: 38802732 PMCID: PMC11131324 DOI: 10.1186/s12263-024-00740-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 02/10/2024] [Indexed: 05/29/2024]
Abstract
Mitochondrial respiration complexes play a crucial function. As a result, dysfunction or change is intimately associated with many different diseases, among them cancer. The epigenetic, evolutionary, and metabolic effects of mitochondrial complex IΙ are the primary concerns of our review. Provides novel insight into the vital role of naringenin (NAR) as an intriguing flavonoid phytochemical in cancer treatment. NAR is a significant phytochemical that is a member of the flavanone group of polyphenols and is mostly present in citrus fruits, such as grapefruits, as well as other fruits and vegetables, like tomatoes and cherries, as well as foods produced from medicinal herbs. The evidence that is now available indicates that NAR, an herbal remedy, has significant pharmacological qualities and anti-cancer effects. Through a variety of mechanisms, including the induction of apoptosis, cell cycle arrest, restriction of angiogenesis, and modulation of several signaling pathways, NAR prevents the growth of cancer. However, the hydrophobic and crystalline structure of NAR is primarily responsible for its instability, limited oral bioavailability, and water solubility. Furthermore, there is no targeting and a high rate of breakdown in an acidic environment. These shortcomings are barriers to its efficient medical application. Improvement targeting NAR to mitochondrial complex ΙΙ by loading it on chitosan nanoparticles is a promising strategy.
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Affiliation(s)
- Eman M Ragab
- Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt.
| | - Abeer A Khamis
- Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt.
| | - Doaa M El Gamal
- Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt
| | - Tarek M Mohamed
- Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt
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Elmoslemany AM, Elzallat M, Abd-Elfatah MH, Mohammed DM, Elhady EE. Possible therapeutic effect of frankincense (Gum olibanum) and myrrh (Commiphora myrrha) resins extracts on DEN/CCL4 induced hepatocellular carcinoma in rats. PHYTOMEDICINE PLUS 2024; 4:100517. [DOI: 10.1016/j.phyplu.2023.100517] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/10/2024]
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Akaras N, Ileriturk M, Gur C, Kucukler S, Oz M, Kandemir FM. The protective effects of chrysin on cadmium-induced pulmonary toxicity; a multi-biomarker approach. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:89479-89494. [PMID: 37453011 DOI: 10.1007/s11356-023-28747-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 07/07/2023] [Indexed: 07/18/2023]
Abstract
This study aimed to determine the potential protective effects of chrysin (CHR) on experimental cadmium (Cd)-induced lung toxicity in rats. To this end, rats were divided into five groups; Control, CHR, Cd, Cd + CHR25, Cd + CHR50. In the study, rats were treated with CHR (oral gavage, 25 mg/kg and 50 mg/kg) 30 min after giving Cd (oral gavage, 25 mg/kg) for 7 consecutive days. The effects of Cd and CHR treatments on oxidative stress, inflammatory response, ER stress, apoptosis and tissue damage in rat lung tissues were determined by biochemical and histological methods. Our results revealed that CHR therapy for Cd-administered rats could significantly reduce MDA levels in lung tissue while significantly increasing the activity of antioxidant enzymes (SOD, CAT, GPx) and GSH levels. CHR agent exerted antiinflammatory effect by lowering elevated levels of NF-κB, IL-1β IL-6, TNF-α, RAGE and NRLP3 in Cd-induced lung tissue. Moreover CHR down-regulated Cd-induced ER stress markers (PERK, IRE1, ATF6, CHOP, and GRP78) and apoptosis markers (Caspase-3, Bax) lung tissue. CHR up-regulated the Bcl-2 gene, an anti-apoptotic marker. Besides, CHR attenuated the side effects caused by Cd by modulating histopathological changes such as hemorrhage, inflammatory cell infiltration, thickening of the alveolar wall and collagen increase. Immunohistochemically, NF-κB and Caspase-3 expressions were intense in the Cd group, while these expressions were decreased in the Cd + CHR groups. These results suggest that CHR exhibits protective effects against Cd-induced lung toxicity in rats by ameliorating oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress and histological changes.
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Affiliation(s)
- Nurhan Akaras
- Department of Histology and Embryology, Faculty of Medicine, Aksaray University, Aksaray, Turkey.
| | - Mustafa Ileriturk
- Department of Animal Science, Horasan Vocational College, Atatürk University, Erzurum, Turkey
| | - Cihan Gur
- Department of Biochemistry, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey
| | - Sefa Kucukler
- Department of Biochemistry, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey
| | - Mehmet Oz
- Department of Physiology, Faculty of Medicine, Aksaray University, Aksaray, Turkey
| | - Fatih Mehmet Kandemir
- Department of Medical Biochemistry, Faculty of Medicine, Aksaray University, Aksaray, Turkey
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Ragab EM, El Gamal DM, Mohamed TM, Khamis AA. Impairment of electron transport chain and induction of apoptosis by chrysin nanoparticles targeting succinate-ubiquinone oxidoreductase in pancreatic and lung cancer cells. GENES & NUTRITION 2023; 18:4. [PMID: 36906524 PMCID: PMC10008604 DOI: 10.1186/s12263-023-00723-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 02/25/2023] [Indexed: 03/13/2023]
Abstract
BACKGROUND Flavonoids may help ameliorate the incidence of the major causes of tumor-related mortality, such as pancreatic ductal adenocarcinoma (PDAC) and lung cancer, which are predicted to steadily increase between 2020 to 2030. Here we compared the effect of chrysin and chrysin nanoparticles (CCNPs) with 5-fluorouracil (5-FLU) on the activity and expression of mitochondrial complex II (CII) to induce apoptosis in pancreatic (PANC-1) and lung (A549) cancer cells. METHODS Chrysin nanoparticles (CCNPs) were synthesized and characterized, and the IC50 was evaluated in normal, PANC-1, and A549 cell lines using the MTT assay. The effect of chrysin and CCNPs on CΙΙ activity, superoxide dismutase activity, and mitochondria swelling were evaluated. Apoptosis was assessed using flow cytometry, and expression of the C and D subunits of SDH, sirtuin-3 (SIRT-3), and hypoxia-inducible factor (HIF-1α) was evaluated using RT-qPCR. RESULTS The IC50 of CII subunit C and D binding to chrysin was determined and used to evaluate the effectiveness of treatment on the activity of SDH with ubiquinone oxidoreductase. Enzyme activity was significantly decreased (chrysin < CCNPs < 5-FLU and CCNPs < chrysin < 5-FLU, respectively), which was confirmed by the significant decrease of expression of SDH C and D, SIRT-3, and HIF-1α mRNA (CCNPs < chrysin < 5-FLU). There was also a significant increase in the apoptotic effects (CCNPs > chrysin > 5-FLU) in both PANC-1 and A549 cells and a significant increase in mitochondria swelling (CCNPs < chrysin < 5-FLU and CCNPs > chrysin > 5-FLU, respectively) than that in non-cancerous cells. CONCLUSION Treatment with CCNPs improved the effect of chrysin on succinate-ubiquinone oxidoreductase activity and expression and therefore has the potential as a more efficient formulation than chemotherapy to prevent metastasis and angiogenesis by targeting HIF-1α in PDAC and lung cancer.
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Affiliation(s)
- Eman M Ragab
- Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt
| | - Doaa M El Gamal
- Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt
| | - Tarek M Mohamed
- Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt
| | - Abeer A Khamis
- Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt.
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Ragab EM, El Gamal DM, Mohamed TM, Khamis AA. Study of the inhibitory effects of chrysin and its nanoparticles on mitochondrial complex II subunit activities in normal mouse liver and human fibroblasts. J Genet Eng Biotechnol 2022; 20:15. [PMID: 35089446 PMCID: PMC8795958 DOI: 10.1186/s43141-021-00286-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 12/13/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Mitochondrial complex ΙΙ has a unique biological role owing to its participation in both the citric acid cycle and the electron transport chain. Our goal was to evaluate the succinate dehydrogenase and ubiquinone oxidoreductase activity of mitochondrial complex II in the presence of chrysin and chrysin-chitosan nanoparticles. Chrysin chitosan nanoparticles were synthesized and characterized using ultraviolet spectroscopy, Fourier transform-infrared spectroscopy, X-ray diffraction, transmission electron microscopy, scanning electron microscopy, drug release, and zeta potential. The binding affinity of chrysin to complex II subunits was assessed by molecular docking. The IC50 values were measured in a suspension of mouse mitochondria, and the inhibitory effect of chrysin and chrysin chitosan nanoparticles on mitochondrial complex ΙΙ was determined. RESULTS The free energy of binding between chrysin and complex ΙΙ subunits A, B, C, and D was -4.9, -5, -8.2, and -8.4 kcal/mol, respectively. The characteristic peak of chrysin was confirmed at 348 nm. The chrysin chitosan nanoparticles contained characteristic bands of both chrysin and chitosan. The crystalline nature of chrysin chitosan nanoparticles was confirmed by X-ray powder diffraction measurements showing the characteristic Bragg peaks of (11.2°), (32.2°), (19.6°), (27.6°), and (31.96°). Transmission and scanning electron microscopy revealed their spherical shape and an average particle size of 49.7 ± 3.02 nm. Chrysin chitosan nanoparticles showed a burst release within the initial 2 h followed by a steady release at 8 h. Their zeta potential was positive, between +35.5 and +80 mV. The IC50 of chrysin, chitosan nanoparticles, chrysin chitosan nanoparticles, and 5-fluorouracil was 34.66, 184.1, 12.2, and 0.05 μg/mL, respectively, in adult mice liver and 129, 311, 156, and 8.07 μg/mL, respectively, in normal human fibroblasts. When comparing the inhibitory effects on complex ΙΙ activity, application of the IC50 of chrysin, chitosan nanoparticles, chrysin chitosan nanoparticles, and 5-fluorouracil resulted in 40.14%, 90.9%, 86.7%, and 89% decreases in SDH activity and 70.09%, 86.74%, 60.8%, and 80.23% decreases in ubiquinone oxidoreductase activity in normal adult mice, but 80.9%, 89.06%, and 90% significant decreases in SDH activity, and 90%, 85%, and 95% decreases in ubiquinone reductase after treatment with chrysin, chrysin chitosan nanoparticles, and 5-fluorouracil, in normal human fibroblasts, respectively. CONCLUSIONS Chrysin and CCNPs exhibit potent inhibitory effects on SDH activity ubiquinone oxidoreductase activity.
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Affiliation(s)
- Eman M Ragab
- Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt
| | - Doaa M El Gamal
- Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt
| | - Tarek M Mohamed
- Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt
| | - Abeer A Khamis
- Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt.
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Malla RR, Marni R, Chakraborty A. ROS-mediated pathways: potential role in hepatocellular carcinoma biology and therapy. THERANOSTICS AND PRECISION MEDICINE FOR THE MANAGEMENT OF HEPATOCELLULAR CARCINOMA, VOLUME 2 2022:321-335. [DOI: 10.1016/b978-0-323-98807-0.00004-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Wei J, Sun Z, Shi L, Hu S, Liu D, Wei H. Molecular Mechanism of Chrysin in Hepatocellular Carcinoma Treatment Based on Network Pharmacology and in Vitro Experiments. Nat Prod Commun 2021. [DOI: 10.1177/1934578x211067294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
This study elucidated the potential molecular mechanism of chrysin in hepatocellular carcinoma (HCC) treatment using network pharmacology and in vitro experiments. Chrysin and candidate targets of HCC were obtained from the TCMSP and DrugBank databases, followed by mapping and screening of chrysin and HCC targets to identify the core targets of chrysin in HCC treatment. The interaction of chrysin and its targets, including CDK1, CDK5, as well as MMP9, were evaluated by molecular docking. The STRING database and Cytoscape (version 3.8.2) software were used to construct protein interactions and component-target networks of the core targets. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis of the core target genes were performed using the DAVID database. Network pharmacology results showed that chrysin treatment of HCC was mainly related to cell proliferation and cell cycle. Accordingly, the cell counting kit-8 method and flow cytometry were used to detect the cell viability and cell cycle of hepatocarcinoma cells HCCLM3 and BEL-7402 in vitro. A total of 142 compound targets of chrysin, 12,179 HCC-related targets, and 116 intersecting targets were screened. The first 20 GO biological annotations of 17 core targets and the first 20 KEGG pathways mainly involved cell proliferation and cell cycle. In vitro experiments showed that chrysin inhibits the proliferation of human hepatocarcinoma cells (HCCLM3 and BEL-7402) in a dose-dependent manner. Moreover, chrysin induced cell cycle arrest in HCCLM3 and BEL-7402 cells in the G2 phase, and the expression was downregulated of cyclin-dependent kinases (CDKs), CDK2 and CDK4. Chrysin can offset HCC mainly by regulating the cell cycle and inhibiting cell proliferation. The network pharmacology results were verified, providing the basis for further study on the mechanism of chrysin intervention in HCC.
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Affiliation(s)
- Jialin Wei
- Changchun University of Chinese Medicine, Changchun, China
| | - Zhiyuan Sun
- Changchun University of Chinese Medicine, Changchun, China
| | - Li Shi
- Changchun University of Chinese Medicine, Changchun, China
| | - Shaodan Hu
- Changchun University of Chinese Medicine, Changchun, China
| | - Da Liu
- Changchun University of Chinese Medicine, Changchun, China
- Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China
| | - Hong Wei
- Changchun University of Chinese Medicine, Changchun, China
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Liang H, Wu JG, Wang F, Chen BX, Zou ST, Wang C, Luo SW. Expression of caspase-3 and hypoxia inducible factor 1α in hepatocellular carcinoma complicated by hemorrhage and necrosis. World J Clin Cases 2021; 9:6725-6733. [PMID: 34447819 PMCID: PMC8362518 DOI: 10.12998/wjcc.v9.i23.6725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 04/08/2021] [Accepted: 05/15/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a malignant tumor that occurs in the liver. Its onset is latent, and it shows high heterogeneity and can readily experience intrahepatic metastasis or systemic metastasis, which seriously affects patients’ quality of life. Numerous studies have shown that hypoxia inducible factor1α (HIF-1α) plays a significant role in the occurrence and development of tumors, as it promotes the formation of intratumoral vessels and plays a key role in their metastasis and invasion. Some studies have reported that caspase-3, which is induced by various factors, is involved in the apoptosis of tumor cells.
AIM To investigate the expression of caspase-3 and HIF-1α and their relationship to the prognosis of patients with primary HCC complicated by pathological changes of hemorrhage and necrosis.
METHODS A total of 88 patients with HCC complicated by pathological changes of hemorrhage and necrosis who were treated at our hospital from January 2017 to December 2019 were selected. The expression of caspase-3 and HIF-1α in HCC and paracancerous tissues from these patients was assessed.
RESULTS The positive expression rate of caspase-3 in HCC tissues was 27.27%, which was significantly lower than that in the paracancerous tissues (P < 0.05), while the positive expression rate of HIF-1α was 72.73%, which was significantly higher than that in the paracancerous tissues (P < 0.05). The positive expression rates for caspase-3 in tumor node metastasis (TNM) stage III and lymph node metastasis tissues were 2.78% and 2.50%, respectively, which were significantly lower than those in TNM stage I-II and non-lymph node metastasis tissues (P < 0.05). The positive expression rates of HIF-1α in TNM stage III, lymph node metastasis, and portal vein tumor thrombus tissues were 86.11%, 87.50%, and 88.00%, respectively, and these values were significantly higher than those in TNM stage I-II, non-lymph node metastasis, and portal vein tumor thrombus tissues (P < 0.05). The expression of caspase-3 and HIF-1α in HCC tissues were negatively correlated (rs = − 0.426, P < 0.05). The median overall survival time of HCC patients was 18.90 mo (95% CI: 17.20–19.91). The results of the Cox proportional risk regression model analysis showed that TNM stage, portal vein tumor thrombus, lymph node metastasis, caspase-3 expression, and HIF-1α expression were the factors influencing patient prognosis (P < 0.05).
CONCLUSION The expression of caspase-3 decreases and HIF-1α increases in HCC tissues complicated by pathological changes of hemorrhage and necrosis, and these are related to clinicopathological features and prognosis.
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Affiliation(s)
- Hui Liang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Jian-Guo Wu
- Department of Nuclear Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Fei Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Bo-Xuan Chen
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Shi-Tian Zou
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Cong Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Shuai-Wu Luo
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
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Anticancer Activity of Propolis and Its Compounds. Nutrients 2021; 13:nu13082594. [PMID: 34444754 PMCID: PMC8399583 DOI: 10.3390/nu13082594] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 07/24/2021] [Accepted: 07/26/2021] [Indexed: 12/13/2022] Open
Abstract
Propolis is a natural material that honey bees (Apis mellifera) produce from various botanical sources. The therapeutic activity of propolis, including antibacterial, antifungal, and anti-inflammatory effects, have been known since antiquity. Cancer is one of the major burdens of disease worldwide, therefore, numerous studies are being conducted to develop new chemotherapeutic agents and treatments for cancer. Propolis is a rich source of biologically active compounds, which affect numerous signaling pathways regulating crucial cellular processes. The results of the latest research show that propolis can inhibit proliferation, angiogenesis, and metastasis of cancer cells and stimulate apoptosis. Moreover, it may influence the tumor microenvironment and multidrug resistance of cancers. This review briefly summarizes the molecular mechanisms of anticancer activity of propolis and its compounds and highlights the potential benefits of propolis to reduce the side effects of chemotherapy and radiotherapy.
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Talebi M, Talebi M, Farkhondeh T, Simal-Gandara J, Kopustinskiene DM, Bernatoniene J, Samarghandian S. Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin. Cancer Cell Int 2021; 21:214. [PMID: 33858433 PMCID: PMC8050922 DOI: 10.1186/s12935-021-01906-y] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Accepted: 04/07/2021] [Indexed: 02/07/2023] Open
Abstract
Chrysin has been shown to exert several beneficial pharmacological activities. Chrysin has anti-cancer, anti-viral, anti-diabetic, neuroprotective, cardioprotective, hepatoprotective, and renoprotective as well as gastrointestinal, respiratory, reproductive, ocular, and skin protective effects through modulating signaling pathway involved in apoptosis, oxidative stress, and inflammation. In the current review, we discussed the emerging cellular and molecular mechanisms underlying therapeutic indications of chrysin in various cancers. Online databases comprising Scopus, PubMed, Embase, ProQuest, Science Direct, Web of Science, and the search engine Google Scholar were searched for available and eligible research articles. The search was conducted by using MeSH terms and keywords in title, abstract, and keywords. In conclusion, experimental studies indicated that chrysin could ameliorate cancers of the breast, gastrointestinal tract, liver and hepatocytes, bladder, male and female reproductive systems, choroid, respiratory tract, thyroid, skin, eye, brain, blood cells, leukemia, osteoblast, and lymph. However, more studies are needed to enhance the bioavailability of chrysin and evaluate this agent in clinical trial studies.
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Affiliation(s)
- Marjan Talebi
- Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, 1991953381, Tehran, Iran
| | - Mohsen Talebi
- Department of Chemistry and Biochemistry, University of Texas at Arlington, Arlington, TX, 76019, USA
- Food Safety Net Services (FSNS), San Antonio, TX, 78216, USA
| | - Tahereh Farkhondeh
- Cardiovscular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
- Faculty of Pharmacy, Birjand University of Medical Sciences, Birjand, Iran
| | - Jesus Simal-Gandara
- Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Science, University of Vigo, Ourense Campus, 32004, Ourense, Spain
| | - Dalia M Kopustinskiene
- Institute of Pharmaceutical Technologies, Faculty of Pharmacy, Medical Academy, Lithuanian University of Health Sciences, Sukileliu pr. 13, 50161, Kaunas, Lithuania
| | - Jurga Bernatoniene
- Institute of Pharmaceutical Technologies, Faculty of Pharmacy, Medical Academy, Lithuanian University of Health Sciences, Sukileliu pr. 13, 50161, Kaunas, Lithuania
| | - Saeed Samarghandian
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran.
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Natural Products Targeting the Mitochondria in Cancers. Molecules 2020; 26:molecules26010092. [PMID: 33379233 PMCID: PMC7795732 DOI: 10.3390/molecules26010092] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 12/23/2020] [Accepted: 12/25/2020] [Indexed: 12/13/2022] Open
Abstract
There are abundant sources of anticancer drugs in nature that have a broad prospect in anticancer drug discovery. Natural compounds, with biological activities extracted from plants and marine and microbial metabolites, have significant antitumor effects, but their mechanisms are various. In addition to providing energy to cells, mitochondria are involved in processes, such as cell differentiation, cell signaling, and cell apoptosis, and they have the ability to regulate cell growth and cell cycle. Summing up recent data on how natural products regulate mitochondria is valuable for the development of anticancer drugs. This review focuses on natural products that have shown antitumor effects via regulating mitochondria. The search was done in PubMed, Web of Science, and Google Scholar databases, over a 5-year period, between 2015 and 2020, with a keyword search that focused on natural products, natural compounds, phytomedicine, Chinese medicine, antitumor, and mitochondria. Many natural products have been studied to have antitumor effects on different cells and can be further processed into useful drugs to treat cancer. In the process of searching for valuable new drugs, natural products such as terpenoids, flavonoids, saponins, alkaloids, coumarins, and quinones cover the broad space.
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Salimi A, Saboji M, Seydi E. Synergistic Effects of Ellagic Acid and Sorafenib on Hepatocytes and Mitochondria Isolated from a Hepatocellular Carcinoma Rat Model. Nutr Cancer 2020; 73:2460-2468. [DOI: 10.1080/01635581.2020.1829653] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Ahmad Salimi
- Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Mojdeh Saboji
- Department of Biology, Plant Physiology, Faculty of Science, Payame Noor University, Tehran, Iran
| | - Enayatollah Seydi
- Department of Occupational Health and Safety Engineering, School of Health, Alborz University of Medical Sciences, Karaj, Iran
- Research Center for Health, Safety and Environment, Alborz University of Medical Sciences, Karaj, Iran
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Moghadam ER, Ang HL, Asnaf SE, Zabolian A, Saleki H, Yavari M, Esmaeili H, Zarrabi A, Ashrafizadeh M, Kumar AP. Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives. Biomolecules 2020; 10:E1374. [PMID: 32992587 PMCID: PMC7600196 DOI: 10.3390/biom10101374] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 09/21/2020] [Accepted: 09/23/2020] [Indexed: 02/06/2023] Open
Abstract
Pharmacological profile of phytochemicals has attracted much attention to their use in disease therapy. Since cancer is a major problem for public health with high mortality and morbidity worldwide, experiments have focused on revealing the anti-tumor activity of natural products. Flavonoids comprise a large family of natural products with different categories. Chrysin is a hydroxylated flavonoid belonging to the flavone category. Chrysin has demonstrated great potential in treating different disorders, due to possessing biological and therapeutic activities, such as antioxidant, anti-inflammatory, hepatoprotective, neuroprotective, etc. Over recent years, the anti-tumor activity of chrysin has been investigated, and in the present review, we provide a mechanistic discussion of the inhibitory effect of chrysin on proliferation and invasion of different cancer cells. Molecular pathways, such as Notch1, microRNAs, signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappaB (NF-κB), PI3K/Akt, MAPK, etc., as targets of chrysin are discussed. The efficiency of chrysin in promoting anti-tumor activity of chemotherapeutic agents and suppressing drug resistance is described. Moreover, poor bioavailability, as one of the drawbacks of chrysin, is improved using various nanocarriers, such as micelles, polymeric nanoparticles, etc. This updated review will provide a direction for further studies in evaluating the anti-tumor activity of chrysin.
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Affiliation(s)
- Ebrahim Rahmani Moghadam
- Department of Anatomical Sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran;
| | - Hui Li Ang
- Cancer Science Institute of Singapore and Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore;
| | - Sholeh Etehad Asnaf
- Department of Cell and Molecular Biology, Faculty of Biological Sciences, North Tehran Branch, IslamicAzad University, Tehran 165115331, Iran;
| | - Amirhossein Zabolian
- Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran 1916893813, Iran; (A.Z.); (H.S.); (H.E.)
| | - Hossein Saleki
- Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran 1916893813, Iran; (A.Z.); (H.S.); (H.E.)
| | - Mohammad Yavari
- Nursing and Midwifery Department, Islamic Azad University, Tehran Medical Sciences Branch, Tehran 1916893813, Iran;
| | - Hossein Esmaeili
- Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran 1916893813, Iran; (A.Z.); (H.S.); (H.E.)
| | - Ali Zarrabi
- Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, Istanbul 34956, Turkey
| | - Milad Ashrafizadeh
- Faculty of Veterinary Medicine, University of Tabriz, Tabriz 5166616471, Iran
| | - Alan Prem Kumar
- Cancer Science Institute of Singapore and Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore;
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