Basic Study
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World J Clin Oncol. May 24, 2023; 14(5): 203-214
Published online May 24, 2023. doi: 10.5306/wjco.v14.i5.203
Thymoquinone enhances the antioxidant and anticancer activity of Lebanese propolis
Sima AlDreini, Zaynab Fatfat, Najwa Abou Ibrahim, Maamoun Fatfat, Hala Gali-Muhtasib, Hala Khalife
Sima AlDreini, Najwa Abou Ibrahim, Hala Khalife, Rammal Rammal Laboratory (ATAC Group), Faculty of Sciences I, Hadath 1003, Lebanon
Zaynab Fatfat, Maamoun Fatfat, Hala Gali-Muhtasib, Department of Biology, American University of Beirut, Beirut 1107-2020, Lebanon
Hala Khalife, Applied Biochemistry Laboratory, School of Pharmacy, Camerino University, Camerino 62032, Italy
Author contributions: AlDreini S carried out lab work as part of her MSc thesis, performed analysis and interpretation of data; Fatfat Z drafted the manuscript; Abou Ibrahim N provided propolis, and contributed intellectually to the study; Fatfat M supervised the experimental work; 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 University and the Undergraduate Research Experience funds at the American University of Beirut.
Institutional review board statement: There was no need to provide an Institutional Review Board Approval Form or Document since no human or animal subjects were involved in this study.
Conflict-of-interest statement: All the authors declare no conflicts of interest.
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:
Corresponding author: Hala Khalife, PhD, Professor, Rammal Rammal Laboratory (ATAC Group), Faculty of Sciences I, Rafic Hariri University Campus, Hadath 1003, Lebanon and Applied Biochemistry Laboratory, School of Pharmacy, Camerino University, Camerino 62032, Italy.
Received: December 28, 2022
Peer-review started: December 28, 2022
First decision: March 15, 2023
Revised: March 24, 2023
Accepted: April 12, 2023
Article in press: April 12, 2023
Published online: May 24, 2023

Reactive oxygen species (ROS) are produced by multiple cellular processes and are maintained at optimal levels in normal cells by endogenous antioxidants. In recent years, the search for potential exogenous antioxidants from dietary sources has gained considerable attention to eliminate excess ROS that is associated with oxidative stress related diseases including cancer. Propolis, a resinous honeybee product, has been shown to have protective effects against oxidative stress and anticancer effects against several types of neoplasms.


To investigate the antioxidant and anticancer potential of Lebanese propolis when applied alone or in combination with the promising anticancer compound Thymoquinone (TQ) the main constituent of Nigella sativa essential oil.


Crude extracts of Lebanese propolis collected from two locations, Rashaya and Akkar-Danniyeh, were prepared in methanol and the total phenolic content was determined by Folin–Ciocalteu method. The antioxidant activity was assessed by the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical and to inhibit H2O2-induced oxidative hemolysis of human erythrocytes. The anticancer activity was evaluated by [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide] MTT assay against HCT-116 human colorectal cancer cells and MDA-MB-231 human breast cancer cells.


The total phenolic content of propolis extract from Rashaya and Akkar-Danniyeh were 56.81 µg and 83.503 µg of gallic acid equivalent /mg of propolis, respectively. Both natural agents exhibited strong antioxidant activities as evidenced by their ability to scavenge DPPH free radical and to protect erythrocytes against H2O2-induced hemolysis. They also dose-dependently decreased the viability of both cancer cell lines. The IC50 value of each of propolis extract from Rashaya and Akkar-Danniyeh or TQ was 22.3, 61.7, 40.44 µg/mL for breast cancer cells at 72 h and 33.3, 50.9, 33.5 µg/mL for colorectal cancer cells at the same time point, respectively. Importantly, the inhibitory effects of propolis on DPPH radicals and cancer cell viability were achieved at half its concentration when combined with TQ.


Our results indicate that Lebanese propolis extract has antioxidant and anticancer potential and its combination with TQ could possibly prevent ROS- mediated diseases.

Keywords: Lebanese propolis, Thymoquinone, Combination, Antioxidant activity, Anticancer activity, Phenolic compounds

Core Tip: Combining Thymoquinone with Lebanese propolis enhanced its antioxidant activity and its anticancer effects against breast and colorectal cancer cells. The combination of these natural products could have potential health benefits and could possibly prevent oxidative stress mediated diseases including cancer.