Wei Tian, Ji Xiaowen, Xue Jinsong, Gao Yan, Zhu Xiaomei, Xiao Guiran
School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui 230009, China.
School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, China.
Food Funct. 2021 Jan 7;12(1):387-396. doi: 10.1039/d0fo02107e. Epub 2020 Dec 16.
Black bean seed coat extract (BBSCE) contains a high amount of bioactive compounds which can reduce the risk of cancers, but the underlying mechanism remains poorly understood in vivo. Here using a Drosophila model of a malignant tumor, wherein the activated oncogene Raf (Raf) cooperates with loss-of-function mutations in the conserved tumor suppressor scribble (scrib), we investigated the antitumor mechanism of BBSCE and its main active component cyanidin-3-O-glucoside (C3G) in vivo. The results showed that supplementation of either BBSCE or C3G inhibited the tumor growth and invasion of Rafscrib and extended their survival in a dose dependent manner. Strikingly, the activation of both autonomous and non-autonomous autophagy in tumor flies was significantly reduced by C3G treatment. A further study indicated that C3G exhibited an antitumor effect in vivo by blocking autophagy both in tumor cells and in its microenvironment by inhibiting the JNK pathway. Interestingly, the efficacy of chloroquine (CQ, an autophagy inhibitor used as an antitumor agent) combined with C3G is much better than either C3G or CQ treatment alone. C3G may be combined with CQ to treat cancers and to provide a theoretical basis for functional food or natural medicine development.
黑豆种皮提取物（BBSCE）含有大量生物活性化合物，可降低癌症风险，但体内潜在机制仍知之甚少。在此，我们使用一种恶性肿瘤的果蝇模型，其中激活的癌基因Raf（Raf）与保守的肿瘤抑制基因scribble（scrib）的功能丧失突变协同作用，研究了BBSCE及其主要活性成分花青素-3-O-葡萄糖苷（C3G）在体内的抗肿瘤机制。结果表明，补充BBSCE或C3G均能抑制Rafscrib的肿瘤生长和侵袭，并以剂量依赖的方式延长其生存期。引人注目的是，C3G处理显著降低了肿瘤果蝇中自主和非自主自噬的激活。进一步研究表明，C3G通过抑制JNK途径阻断肿瘤细胞及其微环境中的自噬，从而在体内发挥抗肿瘤作用。有趣的是，氯喹（CQ，一种用作抗肿瘤药物的自噬抑制剂）与C3G联合使用的疗效比单独使用C3G或CQ治疗要好得多。C3G可能与CQ联合用于治疗癌症，并为功能性食品或天然药物开发提供理论依据。
