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Molecules 2016, 21(7), 886; doi:10.3390/molecules21070886

Gingerol Synergizes the Cytotoxic Effects of Doxorubicin against Liver Cancer Cells and Protects from Its Vascular Toxicity

Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21523, Saudi Arabia
Research Centre, King Faisal Specialist Hospital and Research Centre, Jeddah 21499, Saudi Arabia
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
Ministry of Health, Jeddah 21484, Saudi Arabia
Department of Pharmacology, Medical Division, National Research Centre, Giza 12622, Egypt
Author to whom correspondence should be addressed.
Academic Editor: Nancy D. Turner
Received: 5 June 2016 / Revised: 25 June 2016 / Accepted: 1 July 2016 / Published: 8 July 2016
(This article belongs to the Collection Bioactive Compounds)
View Full-Text   |   Download PDF [2237 KB, uploaded 8 July 2016]   |  


Hydroxyphenylalkanes and diarylheptanoids possess potential therapeutic value in different pathophysiological conditions, such as malignancy. In the current study, naturally isolated hydroxyphenylalkane and diarylheptanoid compounds were investigated for potential chemo-modulatory effects in addition to potential vascular protective roles with doxorubicin. Diarylheptanoids showed stronger antioxidant effects, in comparison to hydroxyphenylalkanes, as demonstrated by DPPH assay and amelioration of CCl4-induced disturbed intracellular GSH/GSSG balance. Shogaol and 4′-methoxygingerol showed considerable cytotoxic effects against HCT116, HeLa, HepG2 and MCF7 cells, with IC50 values ranging from 3.1 to 19.4 µM. Gingerol significantly enhanced the cytotoxic profile of doxorubicin against HepG2 and Huh7, cells decreasing its IC50s by 10- and 4-fold, respectively. Cell cycle distribution was studied using DNA cytometry. Doxorubicin alone induced cell accumulation at S-phase and G2/M-phase, while in combination with gingerol it significantly induced cell cycle arrest at the G2/M-phase. Additionally, the vascular protective effect of gingerol against doxorubicin (10 µM) was examined on isolated aortic rings. Co-incubation with 6-gingerol (30 µM) completely blocked the exaggerated vasoconstriction and impaired vascular relaxation induced by doxorubicin. In conclusion, despite its relatively weak antioxidant properties, gingerol protected from DOX-induced vascular damage, apparently not through a ROS scavenging mechanism. Besides, gingerol synergized the cytotoxic effects of DOX against liver cancer cells without influencing the cellular pharmacokinetics. View Full-Text
Keywords: hydroxyphenylalkanes; diarylheptanoids; gingerol; doxorubicin; liver cancer; vascular protection hydroxyphenylalkanes; diarylheptanoids; gingerol; doxorubicin; liver cancer; vascular protection

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Al-Abbasi, F.A.; Alghamdi, E.A.; Baghdadi, M.A.; Alamoudi, A.J.; El-Halawany, A.M.; El-Bassossy, H.M.; Aseeri, A.H.; Al-Abd, A.M. Gingerol Synergizes the Cytotoxic Effects of Doxorubicin against Liver Cancer Cells and Protects from Its Vascular Toxicity. Molecules 2016, 21, 886.

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