T-Type Ca2+ Channel Blocker, KYS05090 Induces Autophagy and Apoptosis in A549 Cells through Inhibiting Glucose Uptake
It has been reported that [3-(1,1'-biphenyl-4-yl)-2-(1-methyl-5-dimethylamino-pentylamino)-3,4-dihydroquinazolin-4-yl]-N-benzylacetamide 2hydrochloride (KYS05090), a selective T-type Ca2+ channel blocker, reduces tumor volume and weight in the A549 xenograft model, but the molecular mechanism o...
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| Format: | Article |
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MDPI AG
2014-07-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/19/7/9864 |
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| author | Hong-Kun Rim Sehyeon Cho Dong-Hyun Shin Kyung-Sook Chung Young-Wuk Cho Jung-Hye Choi Jae Yeol Lee Kyung-Tae Lee |
| author_facet | Hong-Kun Rim Sehyeon Cho Dong-Hyun Shin Kyung-Sook Chung Young-Wuk Cho Jung-Hye Choi Jae Yeol Lee Kyung-Tae Lee |
| author_sort | Hong-Kun Rim |
| collection | DOAJ |
| description | It has been reported that [3-(1,1'-biphenyl-4-yl)-2-(1-methyl-5-dimethylamino-pentylamino)-3,4-dihydroquinazolin-4-yl]-N-benzylacetamide 2hydrochloride (KYS05090), a selective T-type Ca2+ channel blocker, reduces tumor volume and weight in the A549 xenograft model, but the molecular mechanism of cell death has not yet been elucidated. In this study, KYS05090 induced autophagy- and apoptosis-mediated cell death in human lung adenocarcinoma A549 cells. Although KYS05090 decreased intracellular Ca2+ levels, it was not directly related with KYS05090-induced cell death. In addition, KYS05090 generated intracellular reactive oxygen species (ROS) and reduced glucose uptake, and catalase and methyl pyruvate prevented KYS05090-induced cell death. These results indicate that KYS05090 can lead to autophagy and apoptosis in A549 cells through ROS generation by inhibiting glucose uptake. Our findings suggest that KYS05090 has potential chemotherapeutic value for the treatment of lung cancer. |
| first_indexed | 2024-12-13T06:19:35Z |
| format | Article |
| id | doaj.art-78b6e02b64d446159860f045d9ea3936 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-13T06:19:35Z |
| publishDate | 2014-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-78b6e02b64d446159860f045d9ea39362022-12-21T23:56:53ZengMDPI AGMolecules1420-30492014-07-011979864987510.3390/molecules19079864molecules19079864T-Type Ca2+ Channel Blocker, KYS05090 Induces Autophagy and Apoptosis in A549 Cells through Inhibiting Glucose UptakeHong-Kun Rim0Sehyeon Cho1Dong-Hyun Shin2Kyung-Sook Chung3Young-Wuk Cho4Jung-Hye Choi5Jae Yeol Lee6Kyung-Tae Lee7Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, KoreaResearch Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, KoreaDepartment of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, KoreaDepartment of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, KoreaDepartment of Biomedical Science, College of Medical Science, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, KoreaDepartment of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, KoreaResearch Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, KoreaDepartment of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, KoreaIt has been reported that [3-(1,1'-biphenyl-4-yl)-2-(1-methyl-5-dimethylamino-pentylamino)-3,4-dihydroquinazolin-4-yl]-N-benzylacetamide 2hydrochloride (KYS05090), a selective T-type Ca2+ channel blocker, reduces tumor volume and weight in the A549 xenograft model, but the molecular mechanism of cell death has not yet been elucidated. In this study, KYS05090 induced autophagy- and apoptosis-mediated cell death in human lung adenocarcinoma A549 cells. Although KYS05090 decreased intracellular Ca2+ levels, it was not directly related with KYS05090-induced cell death. In addition, KYS05090 generated intracellular reactive oxygen species (ROS) and reduced glucose uptake, and catalase and methyl pyruvate prevented KYS05090-induced cell death. These results indicate that KYS05090 can lead to autophagy and apoptosis in A549 cells through ROS generation by inhibiting glucose uptake. Our findings suggest that KYS05090 has potential chemotherapeutic value for the treatment of lung cancer.http://www.mdpi.com/1420-3049/19/7/9864T-type Ca2+ channelglucoseautophagyapoptosisreactive oxygen species |
| spellingShingle | Hong-Kun Rim Sehyeon Cho Dong-Hyun Shin Kyung-Sook Chung Young-Wuk Cho Jung-Hye Choi Jae Yeol Lee Kyung-Tae Lee T-Type Ca2+ Channel Blocker, KYS05090 Induces Autophagy and Apoptosis in A549 Cells through Inhibiting Glucose Uptake Molecules T-type Ca2+ channel glucose autophagy apoptosis reactive oxygen species |
| title | T-Type Ca2+ Channel Blocker, KYS05090 Induces Autophagy and Apoptosis in A549 Cells through Inhibiting Glucose Uptake |
| title_full | T-Type Ca2+ Channel Blocker, KYS05090 Induces Autophagy and Apoptosis in A549 Cells through Inhibiting Glucose Uptake |
| title_fullStr | T-Type Ca2+ Channel Blocker, KYS05090 Induces Autophagy and Apoptosis in A549 Cells through Inhibiting Glucose Uptake |
| title_full_unstemmed | T-Type Ca2+ Channel Blocker, KYS05090 Induces Autophagy and Apoptosis in A549 Cells through Inhibiting Glucose Uptake |
| title_short | T-Type Ca2+ Channel Blocker, KYS05090 Induces Autophagy and Apoptosis in A549 Cells through Inhibiting Glucose Uptake |
| title_sort | t type ca2 channel blocker kys05090 induces autophagy and apoptosis in a549 cells through inhibiting glucose uptake |
| topic | T-type Ca2+ channel glucose autophagy apoptosis reactive oxygen species |
| url | http://www.mdpi.com/1420-3049/19/7/9864 |
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