Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3, Minatojima, Chuo-ku, Kobe 650-8586, Japan.
Cancer Chemother Pharmacol. 2011 May;67(5):1063-72. doi: 10.1007/s00280-010-1396-8. Epub 2010 Jul 24.
Wogonin, a flavone in the roots of Scutellaria baicalensis, reduced etoposide-induced apoptotic cell death in normal cells, such as bone marrow cells and thymocytes. On the other hand, wogonin potentiated the proapoptotic or cytotoxic action of etoposide in tumor cells, such as Jurkat, HL-60, A549, and NCI-H226. These contradictory actions of wogonin on apoptosis are distinguished by normal or cancer cell types. Wogonin had no effect on apoptosis induced by other anticancer agents in the tumor cells. Thus, the potentiation effect of wogonin was observed only in etoposide-induced apoptosis in tumor cells. In a functional assay for P-glycoprotein (P-gp), wogonin suppressed excretion of calcein, a substrate for P-gp, in these tumor cells. Moreover, wogonin decreased the excretion of radiolabeled etoposide and accordingly increased intracellular content of this agent in the cells. P-gp inhibitors showed a similar potentiation effect on etoposide-induced apoptosis in these tumor cells. Thus, wogonin is likely to potentiate the anticancer action of etoposide due to P-gp inhibition and accumulation of this agent. These findings suggest that wogonin may be a useful chemotherapeutic adjuvant to potentiate the pharmacological action of etoposide and ameliorate its adverse effects.
黄芩中的黄酮类化合物汉黄芩素可减少依托泊苷诱导的正常细胞（如骨髓细胞和胸腺细胞）的凋亡细胞死亡。另一方面，汉黄芩素增强了依托泊苷在肿瘤细胞（如 Jurkat、HL-60、A549 和 NCI-H226）中的促凋亡或细胞毒性作用。汉黄芩素对细胞凋亡的这种矛盾作用可通过正常或癌细胞类型来区分。汉黄芩素对肿瘤细胞中其他抗癌剂诱导的细胞凋亡没有影响。因此，仅在肿瘤细胞中观察到汉黄芩素对依托泊苷诱导的细胞凋亡的增强作用。在 P-糖蛋白 (P-gp) 的功能测定中，汉黄芩素抑制了这些肿瘤细胞中 P-gp 底物钙黄绿素的排泄。此外，汉黄芩素减少了放射性标记的依托泊苷的排泄，从而增加了细胞内该药物的含量。P-gp 抑制剂在这些肿瘤细胞中对依托泊苷诱导的细胞凋亡也显示出类似的增强作用。因此，汉黄芩素可能通过抑制 P-gp 并积累该药物来增强依托泊苷的抗癌作用。这些发现表明，汉黄芩素可能是一种有用的化疗佐剂，可增强依托泊苷的药理作用并减轻其不良反应。
