Osman Abdel-Moneim M, Al-Malki Hamdan S, Al-Harthi Sameer E, El-Hanafy Amr A, Elashmaoui Hassan M, Elshal Mohamed F
Pharmacology Department, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Mol Med Rep. 2015 Jul;12(1):1368-74. doi: 10.3892/mmr.2015.3513. Epub 2015 Mar 19.
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.
结直肠癌（CRC）是全球癌症相关死亡的主要原因之一。顺铂（CIS）是目前使用的最有效的细胞毒性药物之一，已被证明对各种人类恶性肿瘤有效。然而，其临床应用受到有害副作用的限制，包括肾毒性和骨髓抑制。本研究的目的是试图降低CIS的所需剂量，以尽量减少其副作用，并提高其阻止、延缓或逆转致癌作用的能力。此外，本研究旨在使用天然化合物白藜芦醇（RSVL）改善CRC细胞对CIS的耐药性。RSVL（3,4',5-三羟基反式芪）是一种天然存在的多酚，存在于白藜芦（Veratrum grandiflorum O. Loes）的根中，并从其他70多种植物中提取。RSVL可以发挥抗氧化和抗炎活性，并且已被证明在调节与致癌作用相关的众多细胞事件中具有活性。本研究评估了RSVL对亲本和CIS耐药的HCT-116 CRC细胞对顺铂作用的敏感性的影响。以5和20μg/ml的剂量给予CIS，并在存在和不存在RSVL（15μg/ml）的情况下检查CIS细胞毒性、凋亡、细胞周期和顺铂细胞摄取。RSVL处理显示出抗增殖作用，并增强了顺铂对亲本和CIS耐药的HCT-116 CRC细胞生长的细胞毒性作用，半数最大抑制浓度分别为4.20μg/ml和4.72μg/ml。RSVL还导致早期凋亡分数显著增加，并增强了CIS随后的凋亡作用。与单独的CIS处理相比，在存在RSVL的情况下，CIS的细胞摄取显著增加，并且RSVL处理使CIS耐药的HCT-116细胞敏感。总之，RSVL处理增加了CIS对亲本和CIS耐药的HCT-116 CRC细胞生长的细胞毒性活性。
