title: Modulatory role of resveratrol on cytotoxic activity of cisplatin, sensitization and modification of cisplatin resistance in colorectal cancer cells.
abstract: Colorectal cancer (CRC) is a leading cause of cancer-associated mortality worldwide. Cisplatin (CIS) is one of the most active cytotoxic agents in current use and it has proven efficacy against various human malignancies. However, its clinical usefulness has been restricted by detrimental side effects, including nephrotoxicity and myelosuppression. The aim of the present study was to attempt to decrease the required dose of CIS, in order to minimize its side effects, and increase its capability to arrest, delay or reverse carcinogenesis. In addition, the present study aimed to ameliorate CIS-resistance in CRC cells, using the natural compound resveratrol (RSVL). RSVL (3,4', 5-trihydroxy-trans-stilbene) is a naturally occurring polyphenol present in the roots of white hellebore (Veratrum grandiflorum O. Loes) and extracted from >70 other plant species. RSVL can exert antioxidant and anti-inflammatory activities, and it has been shown to be active in the regulation of numerous cellular events associated with carcinogenesis. The present study evaluated the effects of RSVL on sensitization of both parent and CIS-resistant HCT-116 CRC cells to the action of cisplatin. The CIS was administered at a dose of 5 and 20 µg/ml, and CIS cytotoxicity, apoptosis, cell cycle and cisplatin cellular uptake were examined in the presence and absence of RSVL (15 µg/ml). RSVL treatment showed anti-proliferative effects and enhanced the cytotoxic effects of cis against the growth of both parent and CIS-resistant HCT-116 CRC cells, with a half maximal inhibitory concentration of 4.20 µg/ml and 4.72 µg/ml respectively. RSVL also induced a significant increase in the early apoptosis fraction and enhanced the subsequent apoptotic effects of CIS. The cellular uptake of CIS was significantly increased in the presence of RSVL, as compared with CIS treatment alone, and RSVL treatment sensitized the CIS-resistant HCT-116 cells. In conclusion, RSVL treatment increased the cytotoxic activity of CIS against the growth of both parent and CIS-resistant HCT-116 CRC cells.
authors: Pharmacology Department, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
authors: Abdel-Moneim M
authors: AM
authors: Osman
authors: Pharmacology Department, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
authors: Hamdan S
authors: HS
authors: Al-Malki
authors: Pharmacology Department, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
authors: Sameer E
authors: SE
authors: Al-Harthi
authors: Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
authors: Amr A
authors: AA
authors: El-Hanafy
authors: Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
authors: Hassan M
authors: HM
authors: Elashmaoui
authors: Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
authors: Mohamed F
authors: MF
authors: Elshal
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*
chemical_list: D000975:Antioxidants; D013267:Stilbenes; D002945:Cisplatin; D000077185:Resveratrol