Pharmacological Research ( IF 9.1 ) Pub Date : 2020-08-16 , DOI: 10.1016/j.phrs.2020.105157 David W Chan 1 , Mingo Mh Yung 1 , Yau-Sang Chan 1 , Yang Xuan 1 , Huijuan Yang 2 , Dakang Xu 3 , Jin-Biao Zhan 4 , Karen Kl Chan 1 , Tzi-Bun Ng 5 , Hextan Ys Ngan 1
Increasing evidence shows that Traditional Chinese Medicine (TCM) has an obvious appeal for cancer treatment, but there is still a lack of scientific investigation of its underlying molecular mechanisms. Bitter melon or bitter gourd (Momordica charantia) is an edible fruit that is commonly consumed, and it is used to cure different diseases in various ancient folk medical practices. We report that a bioactive protein, MAP30, isolated from bitter melon seeds exhibited potent anticancer and anti-chemoresistant effects on ovarian cancer cells. Functional studies revealed that MAP30 inhibited cancer cell migration, cell invasion, and cell proliferation in various ovarian cancer cells but not normal immortalized ovarian epithelial cells. When administered with cisplatin, MAP30 produced a synergistic effect on cisplatin-induced cell cytotoxicity in ovarian cancer cells. When low doses of cisplatin and MAP30 were co-injected intraperitoneally, a remarkable reduction of tumor dissemination and tumor growth was observed in an ovarian cancer ascites mouse model. Notably, blood tests confirmed that MAP30 did not cause any adverse effects on liver and kidney functions in the treated mice. MAP30 activated AMP-activated protein kinase (AMPK) signaling via CaMKKβ and induced cell cycle arrest in the S-phase. MAP30 modulated cell metabolism of ovarian cancer cells via suppression of GLUT-1/-3-mediated glucose uptake, adipogenesis, and lipid droplet formation in tumor development and progression. MAP30 also induced an increase in intracellular Ca2+ ion concentration, which triggered ROS-mediated cancer cell death via apoptosis and ferroptosis. Collectively, these findings suggest that natural MAP30 is a non-toxic supplement that may enhance chemotherapeutic outcomes and benefit ovarian cancer patients with peritoneal metastases.
中文翻译:
苦瓜的 MAP30 蛋白具有治疗作用,通过改变代谢和诱导铁死亡,与顺铂在体内对卵巢癌具有协同活性。
越来越多的证据表明,中医药对癌症治疗具有明显的吸引力,但对其潜在的分子机制仍缺乏科学调查。苦瓜或苦瓜 ( Momordica charantia)是一种普遍食用的可食用水果,在各种古老的民间医学实践中用于治疗不同的疾病。我们报告说,从苦瓜种子中分离出的一种生物活性蛋白 MAP30 对卵巢癌细胞表现出有效的抗癌和抗化学抗药性。功能研究表明,MAP30 抑制各种卵巢癌细胞中的癌细胞迁移、细胞侵袭和细胞增殖,但不能抑制正常永生化卵巢上皮细胞。当与顺铂一起给药时,MAP30 对顺铂诱导的卵巢癌细胞细胞毒性产生协同作用。当腹腔内共注射低剂量顺铂和 MAP30 时,在卵巢癌腹水小鼠模型中观察到肿瘤扩散和肿瘤生长显着减少。尤其,血液测试证实,MAP30 不会对接受治疗的小鼠的肝肾功能造成任何不良影响。MAP30 通过 CaMKKβ 激活 AMP 活化蛋白激酶 (AMPK) 信号并诱导细胞周期停滞在 S 期。MAP30 通过抑制肿瘤发展和进展中 GLUT-1/-3 介导的葡萄糖摄取、脂肪生成和脂滴形成来调节卵巢癌细胞的细胞代谢。MAP30 还诱导细胞内 Ca 和脂滴形成在肿瘤的发展和进展中。MAP30 还诱导细胞内 Ca 和脂滴形成在肿瘤的发展和进展中。MAP30 还诱导细胞内 Ca2+离子浓度,通过细胞凋亡和铁死亡触发 ROS 介导的癌细胞死亡。总的来说,这些发现表明天然 MAP30 是一种无毒的补充剂,可以增强化疗效果并使患有腹膜转移的卵巢癌患者受益。