مقالات پذیرفته شده در سومین کنگره بین المللی زیست پزشکی
The effect of flavonoid calycopterin on the expression of apoptotic-related genes in two different breast cancer lines
The effect of flavonoid calycopterin on the expression of apoptotic-related genes in two different breast cancer lines
Farnoosh Attari,1,*Hajar Gholipour ,2
1. Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran 2. Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran
Introduction: Breast cancer is one of the most common cause of death related to cancer in women and many reports proved that herbal substrates such as flavonoids are able to induce apoptosis in this type of cancer via their effects on signaling pathways and gene expression. One of these flavonoids is calycopterin with favored antiproliferative properties on cancer cells, while no adverse effect on normal cells was demonstrated. Although the apoptotic effects of several types of flavonoids on many cancer types has been proved formerly, few studies have been conducted on calycopterin and more importantly no data about its influence on breast cancer is presented so far. Hence, our objective was to investigate the apoptotic effect of flavonoid calycopterin and its underlying mechanism in two different breast cancer cells with disparate receptor pattern, MDA-MB-231 and MCF7
Methods: To evaluate the effect of calycopterin on cell viability, MTT assay was employed in two breast cancer lines. Moreover, for quantification of apoptosis occurred in treated cells, annexin/PI assay was done and to analyze gene expressions related to apoptosis Q-PCR technique was performed.
Results: Our MTT data were indicative of reduced proliferation in both cancer lines via calycopterin treatment while no adverse effect was detected on normal cells. To evaluate whether the reduced proliferation was due to apoptosis occurrence, we have employed annexin/PI assay. It is well accepted that in apoptotic cells one of the phospholipids named phosphatidylserine would change its position from the inner leaflet to the outer leaflet of the cell membrane and annexin can bind specifically to this lipid. Our results demonstrated that calycopterin increased apoptotic population of the MDA-MB-231 cells up to 50% compared to the untreated cells. In the case of MCF7 cells calycopterin treatment augmented apoptosis rate to 31% after 72h. To get more insight of the genes involved in the apoptosis induced by calycopterin, we evaluated the expression of some apoptotic genes such as Bax, Bcl2, p53, caspase-3 and caspase-8 in calycopterin treated cell lines. Our data showed that Bax/Bcl2 ratio increased via calycopterin treatment in MDA-MB-231 cell line, whereas no significant change was observed in that of MCF7 cells. Moreover, p53 and caspase-8 declared augmented expression in both cell lines due to calycopterin treatment, while in that of caspase-3 increased expression was detectable just in the MDA-MB-231 cells not in the MCF7 cells.
Conclusion: In summary, our results were indicative of apoptotic effect of flavonoid calycopterin on both breast cancer cell lines, yet the genes involved in apoptosis induction were slightly different in MDA-MB-231 and MCF7 cells. The origin of this dissimilar reaction toward calycopterin in these cell lines can be rooted from their different signaling status which asks for more investigations. Our data promoted the fact that calycopterin induces stronger apoptosis in the triple-negative MDA-MB-231 line compared to MCF7 cells, which makes it a better candidate to treat triple-negative breast cancers.