Hunan Provincial Key Laboratory for Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Chinese Medicine, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (incubation), College of Medicine, Hunan University of Chinese Medicine, Changsha 410208, China.
Department of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine. 913 N. Rutledge Street, Springfield, IL 62794, USA.
Molecules. 2019 Nov 18;24(22):4179. doi: 10.3390/molecules24224179.
Curcumin is an anticancer agent, but adverse effects and low bioavailability are its main drawbacks, which drives efforts in chemical modifications of curcumin. This study evaluated antiproliferative activity and cancer cell selectivity of a curcumin derivative, curcumin nicotinate (CN), in which two niacin molecules were introduced. Our data showed that CN effectively inhibited proliferation and clonogenic growth of colon (HCT116), breast (MCF-7) and nasopharyngeal (CNE2, 5-8F and 6-10B) cancer cells with IC at 27.7 μM, 73.4 μM, 64.7 μM, 46.3 μM, and 31.2 μM, respectively. In cancer cells, CN induced apoptosis and cell cycle arrest at G2/M phase through a p53-mediated mechanism, where p53 was activated, p21 and pro-apoptotic proteins Bid and Bak were upregulated, and PARP was cleaved. In non-transformed human mammary epithelial cells MCF10A, CN at 50 µM had no cytotoxicity and p53 was not activated, but curcumin at 12.5 µM activated p53 and p21 and inhibited MCF10A cell growth. These data suggest that CN inhibits cell growth and proliferation through p53-mediated apoptosis and cell cycle arrest with cancer cell selectivity.
姜黄素是一种抗癌药物，但不良反应和低生物利用度是其主要缺点，这促使人们对姜黄素进行化学修饰。本研究评估了姜黄素衍生物烟酸姜黄素（CN）的增殖抑制活性和癌细胞选择性，其中引入了两个烟酸分子。我们的数据表明，CN 有效抑制了结肠（HCT116）、乳腺（MCF-7）和鼻咽（CNE2、5-8F 和 6-10B）癌细胞的增殖和集落形成，IC 分别为 27.7 μM、73.4 μM、64.7 μM、46.3 μM 和 31.2 μM。在癌细胞中，CN 通过 p53 介导的机制诱导细胞凋亡和 G2/M 期细胞周期阻滞，其中 p53 被激活，p21 和促凋亡蛋白 Bid 和 Bak 上调，PARP 被切割。在非转化的人乳腺上皮细胞 MCF10A 中，50 μM 的 CN 没有细胞毒性，p53 没有被激活，但 12.5 μM 的姜黄素激活了 p53 和 p21，并抑制了 MCF10A 细胞的生长。这些数据表明，CN 通过 p53 介导的凋亡和细胞周期阻滞抑制细胞生长和增殖，具有癌细胞选择性。
