Bis(4-hydroxy-2H-chromen-2-one) Coumarin Induces Apoptosis in MCF-7 Human Breast Cancer Cells Through Aromatase Inhibition

Abstract

Aim: The present investigation aimed to examine the therapeutic potential of the new coumarin derivative bis(4-hydroxy-2H-chromen-2-one) coumarin (4HC) against breast cancer. Materials and Methods: For this purpose, the effects of 4HC treatment on the proliferation of MCF-7 breast cancer cells and on MCF-10a non-cancerous cells were evaluated using a fluorescent assay. Cell cycle distribution and apoptosis were measured by image cytometry. The expression level of aromatase (CYP19A1) and apoptosis-related genes were determined by real-time PCR. Results: MCF-7 mammary cancer cell proliferation was significantly decreased within 24 h after treatment with 4HC at 50 μM, while no effect was observed on the viability of MCF-10a non-cancerous mammary cells. 4HC also increased the percentage of the cells in the G2/M phase, inducing apoptosis. Real-time PCR revealed that 4HC induced MCF-7 mortality through an up-regulation of Bax and a down-regulation of Bcl-2, resulting in an increase in caspase-3 gene expression. The increased expression of apoptosis-related genes was accompanied by a decrease in CYP19A1 gene expression. Conclusion: 4HC selectively inhibits proliferation of MCF-7cells in vitro. Moreover, 4HC has inhibitory effects on aromatase gene expression and promoting effects on apoptosis, in MCF-7 cells.

Synthesis and Antiproliferative Effect of Halogenated Coumarin Derivatives

“…In the present study, it was observed that coumarin 2k determined cell arrest of TPC-1 cells in the G2/M phase, indicating the apoptotic mode of cell death and inhibition of DNA synthesis (S phase reduction). This finding is consistent with previous investigations reporting that coumarins able to induce cytotoxicity by inducing G2/M and S phases arrest in different cancer cell lines [46,47].…”

Latest developments in coumarin-based anticancer agents: mechanism of action and structure–activity relationship studies

“…136) possessed marked antitumor activity against the MCF-7 cancer cell line by inducing cell cycle arrest in the G2/M phase. 209 A series of hydrazide-hydrazone and amide-substituted coumarin derivatives was synthesized and evaluated in vitro for their antitumor activity. 210 Among them, compound 140a (Fig.…”

Targeting Solid Tumors With BTK Inhibitors

“…Coumarins are derivatives of 2H-1-benzopyran-2-one, which naturally occurs in plants as free coumarins or their glycoside derivatives (Kashman et al, 1992;Currens et al, 1996;McKee et al, 1998;Creagh et al, 2001;Shokoohinia et al, 2018;Bhatia and Rawal, 2019;Kawai et al, 2019;Li et al, 2019;Lin et al, 2019;Makowska et al, 2019;Ramdani et al, 2019;Selvaraj et al, 2019;Wang et al, 2019;Zhang and Xu, 2019). Coumarins have been known for their proapoptotic anticancer activity with inhibitory effects on tumor-promoting signal transduction pathways as well as antiviral activity (Kashman et al, 1992;Currens et al, 1996;McKee et al, 1998;Creagh et al, 2001;Shokoohinia et al, 2018;Bhatia and Rawal, 2019;Kawai et al, 2019;Li et al, 2019;Lin et al, 2019;Makowska et al, 2019;Ramdani et al, 2019;Selvaraj et al, 2019;Wang et al, 2019;Zhang and Xu, 2019). The naturally occurring coumarin derivatives, (+)-calanolide A and (-)-calanolide B, have been identified as inhibitors of non-nucleoside HIV-1-specific reverse-transcriptase inhibitory activity (Kashman et al, 1992;Currens et al, 1996;Creagh et al, 2001).…”

“…Several semi-synthetic calanolide derivatives have been developed as antiviral drug candidates (Creagh et al, 2001;Sagiv-Barfi et al, 2015;Chen et al, 2016). Researchers have hybridized coumarin moieties with other anticancer pharmacophores as a strategy of developing novel anticancer drugs (Flavin et al, 1996;Bhatia and Rawal, 2019;Kawai et al, 2019;Lin et al, 2019;Makowska et al, 2019;Ramdani et al, 2019;Selvaraj et al, 2019;Wang et al, 2019;Zhang and Xu, 2019). In addition, some natural coumarins such as Psoralidin (Li et al, 2019) and Osthol (Shokoohinia et al, 2018) have been reported to exhibit potent in vitro and in vivo anticancer activity.…”