Potent anti-angiogenic and cytotoxic effect of conferone on human colorectal adenocarcinoma HT-29 cells

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• 作者：Omid Cheraghi^a ; Gholamreza Dehghan^a ; ^{dehghan2001d@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; ^{gdehghan@tabrizu.ac.ir" class="auth_mail" title="E-mail the corresponding author} ; Majid Mahdavi^a ; Reza Rahbarghazi^b ; Aysa Rezabakhsh^c ; Hojjatollah Nozad Charoudeh^b ; Mehrdad Iranshahi^d ; Soheila Montazersaheb^e ; ^b
• 关键词：Conferone ; P-glycoprotein ; Angiopoietin-1 ; Reactive oxygen species ; Colorectal adenocarcinoma
• 刊名：Phytomedicine
• 出版年：2016
• 出版时间：15 April 2016
• 年：2016
• 卷：23
• 期：4
• 页码：398-405
• 全文大小：3136 K

文摘

Cancer is one of the leading causes of death worldwide, both in developed and developing countries. Of note, colorectal adenoma encompasses a high rate of gastrointestinal-associated cancer death in human being. Today, different strategies, including surgery approaches, photodynamic therapy, radiation and particularly natural compounds have been extensively used to manage tumor behavior in human body.

Methods

The objective of the present study was to elucidate the multilateral effects of conferone on HT-29 cell lines. In addition to cell cytotoxicity, the extent of lipid peroxidation, MDA formation, catalase, superoxide dismutase and intracellular ROS levels, as markers of oxidative stress, were also studied. P-glycoprotein-mediated cellular efflux effectiveness, anti-angiogenic and finally anti-migratory capacities of conferone-exposed HT-29 cells were monitored over a course of 72 h.

Results

It was found that, conferone mediated cell proliferation arrest and induced cell death through both apoptosis and necrosis phenomena. HT-29 cells, exposed to 20 µM conferone, under gone oxidative stress and total content of reactive oxygen species was increased in a time-dependent manner. Intracellular accumulation of rhodamine 123 and cell's swelling under iso- and hypo-osmotic conditions could be related to P-glycoprotein incorrect performance in the presence of conferone. A significant reduction in CD31 positive cells population and in vitro tubulogenesis of endothelial cells was also observed after incubation with conditioned medium collected from 72 h conferone-treated HT-29 cells. Conferone also precluded angiogenesis capability of treated HT-29 cells through an altered secretome profile, including vascular endothelial growth factor, Angiopoietin-1 and -2 factors. In addition to anti-angiogenic properties of conferone, a profound decrease in migration capability of HT-29 cells was also evident.