Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
Int J Mol Sci. 2020 Aug 7;21(16):5669. doi: 10.3390/ijms21165669.
Thailand is the country with highest incidence and prevalence of cholangiocarcinoma (CCA) in the world. Due to the frequently late diagnosis that is associated with this disease, most CCA patients are prescribed chemotherapy as a form of treatment. However, CCA is able to resist the presently available chemotherapy, so to the prognosis of this disease is still very poor. In this study, we investigated the anticancer potential of a Thai herbal recipe, Benja Amarit (BJA) against CCA and the relevant mechanisms of action that are involved. We found that BJA inhibited CCA cell viability in a dose-dependent manner, especially in highly invasive KKU-213 cells. The extract induced mitochondrial- and caspase-dependent apoptosis in CCA cells by regulating the nuclear factor-κB (NF-κB) signaling pathway. BJA also triggered autophagy in CCA cells. Nonetheless, the inhibition of autophagy enhanced BJA-induced CCA cell death via apoptosis. An in vivo xenograft model revealed the growth-inhibiting and death-inducing effects of BJA against CCA by targeting apoptosis. However, general toxicity to blood cells, kidneys and the liver, as well as changes in body weight, did not appear. Our findings suggest that the herbal recipe BJA might be used as a potentially new and effective treatment for cholangiocarcinoma patients.
泰国是世界上胆管癌（CCA）发病率和患病率最高的国家。由于这种疾病常常导致诊断较晚，大多数 CCA 患者被开处化疗作为一种治疗方法。然而，CCA 能够抵抗目前可用的化疗药物，因此该疾病的预后仍然非常差。在这项研究中，我们研究了一种泰国草药配方 Benja Amarit（BJA）对 CCA 的抗癌潜力及其相关作用机制。我们发现 BJA 以剂量依赖的方式抑制 CCA 细胞活力，特别是在高度侵袭性的 KKU-213 细胞中。该提取物通过调节核因子-κB（NF-κB）信号通路诱导 CCA 细胞线粒体依赖性和半胱天冬酶依赖性细胞凋亡。BJA 还在 CCA 细胞中引发自噬。然而，通过凋亡抑制自噬增强了 BJA 诱导的 CCA 细胞死亡。体内异种移植模型显示，BJA 通过靶向细胞凋亡抑制 CCA 的生长和诱导死亡。然而，并没有出现对血细胞、肾脏和肝脏的一般毒性以及体重变化。我们的研究结果表明，草药配方 BJA 可能被用作胆管癌患者的一种潜在的新的有效治疗方法。
