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朝藿定诱导人结直肠癌细胞 HT29 发生 G0/G1 期细胞周期阻滞和线粒体介导的细胞凋亡。

Orientin Induces G0/G1 Cell Cycle Arrest and Mitochondria Mediated Intrinsic Apoptosis in Human Colorectal Carcinoma HT29 Cells.

机构信息

Department of Microbiology and Biotechnology, Bharath Institute of Higher Education and Research, Tamilnadu 600045, India.

Molecular Oncology Lab, Department of Biochemistry, Periyar University, Tamilnadu 636011, India.

出版信息

Biomolecules. 2019 Aug 27;9(9):418. doi: 10.3390/biom9090418.

DOI:10.3390/biom9090418
PMID:31461995
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6770649/
Abstract

Colorectal carcinoma is one of the utmost diagnosed cancer with a steep increase in mortality rate. The incidence has been increasing in developing countries like India due to a westernization life style. Flavonoids have been explored widely for its various pharmacological activity including antitumor activity. Orientin, an analogue of luteolin (citrus flavonoid) isolated from rooibos and tulsi leaves is also expected to deliver significant antitumor activity similar to that of luteolin. The present study anticipates exploring the antitumor activity of orientin against colorectal carcinoma cells (HT29). Orientin exhibited remarkable cytotoxicity and antiproliferative activity against HT29 cells, which is clearly evident from tetrazolium based cytotoxicity and lactate dehydrogenase release assays. Orientin induce G0/G1 cell cycle arrest and regulates cyclin and cyclin-dependent protein kinases in order to prevent the entry of the cell cycle to the S phase. Annexin V-FITC (V-Fluorescein Isothiocyanate) dual staining reveals the apoptotic induction ability of orientin. The Bcl-2 family proteins along with the inhibitor of apoptotic proteins were regulated and the tumor suppressor p-53 expression have been decreased. In conclusion, our results proposed that orientin could be a potent chemotherapeutic agent against colorectal cancer after ascertaining their molecular mechanisms.

摘要

结直肠癌是死亡率急剧上升的最常见癌症之一。由于生活方式的西化，印度等发展中国家的发病率一直在上升。类黄酮因其各种药理活性，包括抗肿瘤活性，已被广泛研究。橙皮苷是从南非路易波士茶和罗勒叶中分离出的木犀草素（柑橘类黄酮）的类似物，也有望具有与木犀草素相似的显著抗肿瘤活性。本研究旨在探索橙皮苷对结直肠癌细胞（HT29）的抗肿瘤活性。橙皮苷对 HT29 细胞表现出显著的细胞毒性和抗增殖活性，这从基于四唑的细胞毒性和乳酸脱氢酶释放测定中可以明显看出。橙皮苷诱导 G0/G1 细胞周期停滞，并调节细胞周期蛋白和细胞周期蛋白依赖性蛋白激酶，以防止细胞周期进入 S 期。Annexin V-FITC（V-异硫氰酸荧光素）双重染色揭示了橙皮苷的诱导凋亡能力。Bcl-2 家族蛋白和凋亡抑制蛋白被调节，肿瘤抑制因子 p-53 的表达减少。总之，我们的研究结果表明，在确定橙皮苷的分子机制后，它可能成为一种有效的结直肠癌化疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdda/6770649/fe0937a8e122/biomolecules-09-00418-g012.jpg
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