Yahuafai Jantana, Asai Tomohiro, Oku Naoto, Siripong Pongpun
Natural Products and Integrative Medicine Research Section, Research Division, National Cancer Institute.
Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences.
Biol Pharm Bull. 2018;41(7):1103-1106. doi: 10.1248/bpb.b17-00989.
Berberine, the main isoquinoline alkaloid obtained from traditional plants, e.g., Berberis, Coptis, Coscinium spps., etc., is known to exhibit anticancer activity in vitro and in vivo. In this study, the anticancer potential of berberine combined with PEGylated liposomal doxorubicin (polyethylene glycol (PEG)-lip-DOX) was investigated. At first, the effect of berberine on endothelial cells was examined in vitro by use of human umbilical vein endothelial cells (HUVECs): Berberine inhibited HUVEC growth with an IC at 24 h of about 144 µg/mL and that at 72 h of about 29 µg/mL. In contrast, less than 50 µg/mL berberine inhibited the vascular endothelial growth factor (VEGF) expression to some extent after a 24-h incubation, suggesting that berberine suppressed angiogenic action under the condition of little cytotoxicity. Next, the in vivo anticancer activity of the combination of berberine (intraperitoneally (i.p.)) and PEG-lip-DOX (intravenously (i.v.)) was examined in Meth A sarcoma-transplanted BALB/c mice. The results showed that either berberine or PEG-lip-DOX exhibited antiproliferative activity against Meth A cells. Moreover, treatment with the combination of berberine and PEG-lip-DOX suppressed the tumor growth more strongly than that with berberine or PEG-lip-DOX alone. Based on these findings, the combination cancer chemotherapy with berberine and PEGylated liposomal doxorubicin may be beneficial for the treatment of cancer.
小檗碱是从传统植物如小檗属、黄连属、古山龙属等植物中提取的主要异喹啉生物碱，已知其在体外和体内均具有抗癌活性。在本研究中，对小檗碱与聚乙二醇化脂质体阿霉素（聚乙二醇（PEG）-脂质体阿霉素）联合使用的抗癌潜力进行了研究。首先，通过人脐静脉内皮细胞（HUVECs）在体外检测小檗碱对内皮细胞的影响：小檗碱抑制HUVEC生长，24小时时的IC约为144μg/mL，72小时时约为29μg/mL。相比之下，孵育24小时后，低于50μg/mL的小檗碱在一定程度上抑制血管内皮生长因子（VEGF）表达，这表明小檗碱在细胞毒性较小的情况下抑制血管生成作用。接下来，在接种了Meth A肉瘤的BALB/c小鼠中检测了小檗碱（腹腔注射（i.p.））和PEG-脂质体阿霉素（静脉注射（i.v.））联合使用的体内抗癌活性。结果表明，小檗碱或PEG-脂质体阿霉素对Meth A细胞均表现出抗增殖活性。此外，小檗碱和PEG-脂质体阿霉素联合治疗比单独使用小檗碱或PEG-脂质体阿霉素更强烈地抑制肿瘤生长。基于这些发现，小檗碱与聚乙二醇化脂质体阿霉素联合进行癌症化疗可能对癌症治疗有益。
