In vitro cytotoxicity on human ovarian cancer cells by T-type calcium channel blockers
- Title
- In vitro cytotoxicity on human ovarian cancer cells by T-type calcium channel blockers
- Authors
- 장선정; 최흥우; 최두리; 조세현; 림홍근; 최혜은; 김기선; 황명화; 임혜원; 이경태; 이재열
- Keywords
- T-type Ca2+ channel; Ovarian cancer; Cytotoxicity; Cell cycle arrest; Apoptosis
- Issue Date
- 2013-12
- Publisher
- Bioorganic & medicinal chemistry letters
- Citation
- VOL 23, NO 24, 6656-6662
- Abstract
- The growth inhibition of human cancer cells via T-type Ca2+ channel blockade has been well known. Herein, a series of new 3,4-dihydroquinazoline derivatives were synthesized via a brief SAR study on KYS05090 template and evaluated for both T-type Ca2+ channel (Cav3.1) blockade and cytotoxicity on three human ovarian cancer cells (SK-OV-3, A2780 and A2780-T). Most of compounds except 6i generally exhibited more potent cytotoxicity on SK-OV-3 than mibefradil as a positive control regardless of the degree of T-type channel blockade. In particular, eight compounds (KYS05090, 6a and 6c–6h) showing strong channel blockade exhibited almost equal and more potent cytotoxicity on A2780 when compared to mibefradil. On A2780-T paclitaxel-resistant human ovarian carcinoma, two compounds (KYS05090 and 6d) were 20-fold more active than mibefradil. With respect to cell cycle arrest effect on A2780 and A2780-T cells, KYS05090 induced large proportion of sub-G1 phase in the cell cycle progression of A2780 and A2780-T, meaning the induction of cancer cell death instead of cell cycle arrest via blocking T-type Ca2+ channel. Among new analogues, compounds 6g and 6h induced cell cycle arrest at G1 phase of A2780 and A2780-T cells in dose-dependent manner and exhibited strong anti-proliferation effects of ovarian cancer cells by blocking T-type Ca2+ channel. Furthermore, 6g and 6h possessing strong cytotoxic effects could induce apoptosis of A2780 cells, which was detected by confocal micrographs using DAPI staining.
- URI
- https://pubs.kist.re.kr/handle/201004/47098
- ISSN
- 0960894X
- Appears in Collections:
- KIST Publication > Article
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