Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA.
J Pharm Pharmacol. 2012 May;64(5):727-34. doi: 10.1111/j.2042-7158.2012.01463.x. Epub 2012 Feb 21.
Panaxadiol is a purified sapogenin of ginseng saponins that exhibits anticancer activity. Irinotecan is a second-line anticancer drug, but clinical treatment with irinotecan is limited due to its side effects. In this study, we have investigated the possible synergistic anticancer effects of panaxadiol and irinotecan on human colorectal cancer cells and explored the potential role of apoptosis in their synergistic activity.
The combination of panaxadiol and irinotecan significantly enhanced antiproliferative effects in HCT-116 cells (P< 0.05). Cell cycle analysis demonstrated that combining irinotecan treatment with panaxadiol significantly increased the G1-phase fractions of cells, compared with irinotecan treatment alone. In apoptotic assays, the combination of panaxadiol and irinotecan significantly increased the percentage of apoptotic cells compared with irinotecan alone (P<0.01). Increased activity of caspase-3 and caspase-9 was observed after treating with panaxadiol and irinotecan. The synergistic apoptotic effects were supported by docking analysis, which demonstrated that panaxadiol and irinotecan bound two different chains of the caspase-3 protein.
Data from this study suggested that caspase-3- and caspase-9-mediated apoptosis may play an important role in the panaxadiol enhanced antiproliferative effects of irinotecan on human colorectal cancer cells.
人参二醇是一种从人参皂苷中提取的纯化甾体皂甙，具有抗癌活性。伊立替康是一种二线抗癌药物，但由于其副作用，临床应用受到限制。在本研究中，我们研究了人参二醇和伊立替康联合应用对人结直肠癌细胞的可能协同抗癌作用，并探讨了凋亡在其协同作用中的潜在作用。
人参二醇和伊立替康联合应用显著增强了 HCT-116 细胞的增殖抑制作用（P<0.05）。细胞周期分析表明，与伊立替康单独治疗相比，联合应用人参二醇显著增加了细胞的 G1 期分数。在凋亡检测中，与伊立替康单独治疗相比，人参二醇和伊立替康联合应用显著增加了凋亡细胞的百分比（P<0.01）。在用人参二醇和伊立替康处理后，观察到 caspase-3 和 caspase-9 的活性增加。对接分析表明，人参二醇和伊立替康结合了 caspase-3 蛋白的两个不同链，支持了协同凋亡作用。
本研究数据表明，caspase-3 和 caspase-9 介导的凋亡可能在人参二醇增强伊立替康对人结直肠癌细胞的增殖抑制作用中发挥重要作用。
