title: Inhibition of cellular proliferation and induction of apoptosis in human lung adenocarcinoma A549 cells by T-type calcium channel antagonist.
abstract: The anti-proliferative and apoptotic activities of new T-type calcium channel antagonist, 6e (BK10040) on human lung adenocarcinoma A549 cells were investigated. The MTT assay results indicated that BK10040 was cytotoxic against human lung adenocarcinoma (A549) and pancreatic cancer (MiaPaCa2) cells in a dose-dependent manner with IC50 of 2.25 and 0.93μM, respectively, which is ca. 2-fold more potent than lead compound KYS05090 despite of its decreased T-type calcium channel blockade. As a mode of action for cytotoxic effect of BK10040 on lung cancer (A549) cells, this cancer cell death was found to have the typical features of apoptosis, as evidenced by the accumulation of positive cells for annexin V. In addition, BK10040 triggered the activations of caspases 3 and 9, and the cleavages of poly (ADP-ribose) polymerase (PARP). Moreover, the treatment with z-VAD-fmk (a broad spectrum caspase inhibitor) significantly prevented BK10040-induced apoptosis. Based on these results, BK10040 may be used as a potential therapeutic agent for human lung cancer via the potent apoptotic activity.
authors: Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Doo Li
authors: DL
authors: Choi
authors: Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Sun Jeong
authors: SJ
authors: Jang
authors: Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Sehyeon
authors: S
authors: Cho
authors: Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Hye-Eun
authors: HE
authors: Choi
authors: Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Hong-Kun
authors: HK
authors: Rim
authors: Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Kyung-Tae
authors: KT
authors: Lee
authors: Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea. Electronic address: ljy@khu.ac.kr.
authors: Jae Yeol
authors: JY
authors: Lee
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000737:chemistry* / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C000592788:BK10040; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; C549128:KYS 05090; D010879:Piperazines; D011799:Quinazolines
keywords: Antagonist; Apoptosis; Caspases; Cell cycle arrest; Human lung adenocarcinoma (A549) cells; Pancreatic cancer (MiaPaCa2) cells; T-type calcium channel