Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. May 24, 2021; 12(5): 342-354
Published online May 24, 2021. doi: 10.5306/wjco.v12.i5.342
Thymoquinone anticancer activity is enhanced when combined with royal jelly in human breast cancer
Maya M Moubarak, Nour Chanouha, Najwa Abou Ibrahim, Hala Khalife, Hala Gali-Muhtasib
Maya M Moubarak, Nour Chanouha, Department of Biology, American University of Beirut, Beirut 1107-2020, Lebanon
Najwa Abou Ibrahim, Hala Khalife, Rammal Rammal Laboratory (ATAC group), Faculty of Sciences I, Hadath 1003, Lebanon
Hala Gali-Muhtasib, Department of Biology and Center for Drug Discovery, American University of Beirut, Beirut 1107-2020, Lebanon
Author contributions: Moubarak MM carried out lab work as part of her MSc thesis, performed analysis and interpretation of data (e.g., biostatistics, statistical analysis and editing), and wrote the first draft of the manuscript; Chanouha N performed initial lab work and determined dose responses and performed data analysis; Abou Ibrahim N brought the importance of royal jelly to the attention of the corresponding author, provided it, and contributed intellectually to the study; Khalife H reviewed the manuscript and contributed in the critical appraisal of data; Gali-Muhtasib H conceived the project, supervised the work, and edited the manuscript draft; All authors have read and approved the final manuscript.
Supported by The Lebanese National Council for Scientific Research and the American University of Beirut, No.103482; and the Undergraduate Research Experience of the Faculty of Arts and Sciences, American University of Beirut.
Conflict-of-interest statement: Authors declare no conflict of interest for this manuscript.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hala Gali-Muhtasib, PhD, Professor, Department of Biology and Center for Drug Discovery, American University of Beirut, Bliss Street, Biology Bldg, Room 207, PO Box 11-0236, Riad El Solh, Lebanon, Beirut 1107-2020, Lebanon. amro@aub.edu.lb
Received: January 28, 2021
Peer-review started: January 28, 2021
First decision: March 1, 2021
Revised: March 13, 2021
Accepted: April 26, 2021
Article in press: April 26, 2021
Published online: May 24, 2021
Processing time: 113 Days and 15.7 Hours
ARTICLE HIGHLIGHTS
Research background

Despite the tremendous improvement in therapeutic approaches, triple-negative breast cancer has poor prognosis. Thymoquinone (TQ), the main constituent of Nigella sativa seeds and royal jelly (RJ), the honeybee secretion fed to honeybee queens, are effective against cancer. However, the anticancer activity of the combination of TQ and RJ against aggressive human breast cancer cells is yet unknown.

Research motivation

To establish novel treatments for breast cancer using natural, relatively non-toxic compounds with significant therapeutic value. We focused on investigating the anticancer activity of TQ and RJ combinations against triple-negative breast cancer.

Research objectives

This study aimed to characterize the anticancer activity of TQ and RJ alone and their combination in vitro against human triple-negative breast cancer.

Research methods

The inhibitory effect of TQ on triple-negative breast cancer cells was assessed by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Trypan blue exclusion assay was used to evaluate cell viability in response to different treatment conditions. Propidium iodide deoxyribonucleic acid staining followed by flow cytometry was performed to evaluate possible cell cycle regulation and cell death effects. Apoptosis and cell proliferation were determined using immunofluorescence assays for cleaved caspase 3 and Ki67 expression, respectively. The interaction between TQ and RJ and combination indices were evaluated using CompuSyn software.

Research results

TQ inhibited MDA-MB-231 breast cancer cell viability in a dose-dependent manner. RJ at low doses was relatively nontoxic to non-tumorigenic FHs 74 Int small intestinal epithelial cells, while at high doses greater toxicity against MDA-MB-231 breast cancer cells was observed. Inhibition of cell viability and cell death effects were more pronounced in response to TQ and RJ combinations compared to each drug alone. The reduction in breast cancer cell viability was mainly due to TQ-mediated caspase 3-dependent apoptosis.

Research conclusions

RJ and TQ are relatively non-toxic to normal cells and exhibited pronounced anticancer effects against human metastatic breast cancer. Although our findings demonstrate the potent pro-apoptotic activity of TQ compared to that of RJ, this is the first report of a significant enhancement in TQ’s anticancer activity when combined with RJ.

Research perspectives

The reduction in breast cancer cell viability and enhanced cell death effects upon TQ and RJ combinations highlights their potential therapy for human triple-negative breast cancer.