Abstract
Abstract
Hydroxyphenylalkanes and diarylheptanoids possess potential therapeutic values in different patho-physiological conditions such as inflammation, oxidative stress, cardiovascular disorders and malignancy. Doxorubicin is widely used chemotherapeutic agent against several types of neoplastic disorders. In the current study, naturally isolated hydroxyphenylalkane and diarylheptanoid compounds were investigated for their potential chemo-modulatory effects on the top of their potential vascular protective role with doxorubicin. Shogaol and 4-methoxygingerol showed considerable cytotoxic effects against HCT116, HeLa, HepG2 and MCF7 cells with IC50 ranging from 3.1 to 18.7 μM and from 9.1 to 19.4 μM, respectively. Using DPPH free radical scavenging assay, diarylheptanoids were stronger antioxidant than hydroxyphenylalkanes with EC50 ranging from 0.5 to 5.9 μM and from 4.6 to 9.5 μM, respectively. In addition, all tested diarylheptanoids significantly ameliorated CCl4 induced disturbed intracellular GSH/GSSG balance. Gingerol moderately enhanced the cytotoxic profile of doxorubicin against HepG2 and Huh7 cells decreasing their IC50's from 0.52 to 0.37 μM and from 50 to 30 nM, respectively. Combination index of gingerol with doxorubicin (combination at equitoxic ratio of 1/100) was indicative of additive interaction (CI-value were 1.1 and 1.0, respectively). To further investigate the interactive characteristics between doxorubicin and gingerol, cell cycle distribution of HepG2 and Huh7 cells was studied using DNA cytometry after exposure to their single and equitoxic combination. Doxorubicin induced cell accumulation at S-phase and G2/M-phase while, gingerol combination with doxorubicin significantly induced cell cycle arrest at G2/M-phase. To study the potential vascular protective effect of gingerol against doxorubicin induced vascular toxicity, doxorubicin (10 μM for 1h) was incubated with or without different concentrations of 6-gingerol (3, 10 and 30 μM for 1h) on isolated aortic rings and their response to phenylephrine (PE) and acetylcholine (ACh) was examined. Co-incubation of 6-gingerol (30 μM) completely blocked the exaggerated vasoconstriction and impaired vascular relaxation induced by doxorubicin
Citation Format: Mohammed A. Baghdadi, Eman A. Al-Ghamdi, Abdulmohsin J. Alamoudi, Fahad A. Al-Abbasi, Hany M. El-Bassossy, Ali M. El-Halawany, Ahmed M. Al-Abd. Chemotherapeutic, chemomodulatory and vascular protective effects of naturally occurring hydroxyphenylalkanes and diarylheptanoids. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2181.