Yin Pei-Hao, Liu Xuan, Qiu Yan-Yan, Cai Jian-feng, Qin Jian-min, Zhu Hui-Rong, Li Qi
Department of General Surgery and Medical Oncology, Putuo Hospital and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Asian Pac J Cancer Prev. 2012;13(11):5339-43. doi: 10.7314/apjcp.2012.13.11.5339.
The induction of apoptosis in target cells is a key mechanism for most anti-tumor therapies. Bufalin is a cardiotonic steroid that has the potential to induce differentiation and apoptosis of tumor cells. Research on bufalin has so far mainly involved leukemia, prostate cancer, gastric cancer and liver cancer, and has been confined to in vitro studies. The bufadienolides bufalin and cinobufagin have been shown to induce apoptosis in a wide spectrum of cancer cell. The present article reviews the anticancer effects of bufalin. It induces apoptosis of lung cancer cells via the PI3K/Akt pathway and also suppressed the proliferation of human non-small cell lung cancer A549 cell line in a time and dose dependent manner. Bufalin, bufotalin and gamabufotalin, key bufadienolides, significantly sensitize human breast cancer cells with differing ER-alpha status to apoptosis induction by the TNF-related apoptosis-inducing ligand (TRAIL). In addition, bufadienolides induce prostate cancer cell apoptosis more significantly than that in breast epithelial cell lines. Similar effects have been observed with hepatocellular carcinoma (HCC) but the detailed molecular mechanisms of inducing apoptosis in this case are still unclear. Bufalin exerts profound effects on leukemia therapy in vitro. Results of multiple studies indicate that bufalin has marked anti-tumor activities through its ability to induce apoptosis. Large-scale randomized, double-blind, placebo or positive drug parallel controlled studies are now required to confirm the efficacy and apoptosis-inducing potential of bufalin in various cancers in the cliniucal setting.
诱导靶细胞凋亡是大多数抗肿瘤治疗的关键机制。蟾毒灵是一种强心甾体，具有诱导肿瘤细胞分化和凋亡的潜力。迄今为止，关于蟾毒灵的研究主要涉及白血病、前列腺癌、胃癌和肝癌，且局限于体外研究。蟾毒配基类化合物蟾毒灵和华蟾酥毒基已被证明可诱导多种癌细胞凋亡。本文综述了蟾毒灵的抗癌作用。它通过PI3K/Akt途径诱导肺癌细胞凋亡，并以时间和剂量依赖的方式抑制人非小细胞肺癌A549细胞系的增殖。蟾毒灵、蟾毒素和γ-蟾毒素等关键蟾毒配基，可显著增强不同雌激素受体α状态的人乳腺癌细胞对肿瘤坏死因子相关凋亡诱导配体（TRAIL）诱导凋亡的敏感性。此外，蟾毒配基诱导前列腺癌细胞凋亡的作用比在乳腺上皮细胞系中更显著。在肝细胞癌（HCC）中也观察到了类似的效果，但在这种情况下诱导凋亡的详细分子机制仍不清楚。蟾毒灵在体外对白血病治疗有深远影响。多项研究结果表明，蟾毒灵通过诱导凋亡的能力具有显著的抗肿瘤活性。现在需要大规模随机、双盲、安慰剂或阳性药物平行对照研究来证实蟾毒灵在临床环境中对各种癌症的疗效和诱导凋亡的潜力。
