Enterocarpam-III induces human liver and breast cancer cell apoptosis via mitochondrial and caspase-9 activation
An aristolactam-type alkaloid, isolated from Orophea enterocarpa, is enterocarpam-III (10-amino-2,3,4,6-tetramethoxyphenanthrene-1-carboxylic acid lactam). It is cytotoxic to various human and murine cancer cell lines; however, the molecular mechanisms remain unclear. The aims of this study were to...
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Asian Pacific Organization for Cancer Prevention
2015
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th-cmuir.6653943832-384682015-06-16T07:47:17Z Enterocarpam-III induces human liver and breast cancer cell apoptosis via mitochondrial and caspase-9 activation Banjerdpongchai,R. Wudtiwai,B. Pompimon,W. Cancer Research Oncology Epidemiology Public Health, Environmental and Occupational Health An aristolactam-type alkaloid, isolated from Orophea enterocarpa, is enterocarpam-III (10-amino-2,3,4,6-tetramethoxyphenanthrene-1-carboxylic acid lactam). It is cytotoxic to various human and murine cancer cell lines; however, the molecular mechanisms remain unclear. The aims of this study were to investigate cytotoxic effects on and mechanism (s) of human cancer cell death in human hepatocellular carcinoma HepG2 and human invasive breast cancer MDA-MB-231 cells compared to normal murine fibroblast NIH3T3 cells. Cell viability was determined by MTT assay to determine IC<inf>10</inf>, IC<inf>20</inf> and IC<inf>50</inf> levels, reactive oxygen species (ROS) production with 2',7'-dichlorohydrofluorescein diacetate and the caspase-3, -8 and -9 activities using specific chromogenic (p-nitroaniline) tetrapeptide substrates, viz., DEVD-NA, IETD-NA and LEHD-NA and employing a microplate reader. Mitochondrial transmembrane potential (MTP) was measured by staining with 3, 3'-dihexyloxacarbocyanine iodide (DiOC<inf>6</inf>) and using flow cytometry. The compound was cytotoxic to HepG2 and MDA-MB-231 cells with the IC<inf>50</inf> levels of 26.0±4.45 and 51.3±2.05 μM, respectively. For murine normal fibroblast NIH3T3 cells, the IC<inf>50</inf> concentration was 81.3±10.1 μM. ROS production was reduced in a dose-response manner in HepG2 cells. The caspase-9 and -3 activities increased in a concentration-dependent manner, whereas caspase-8 activity did not alter, indicating the intrinsic pathway activation. Enterocarpam-III decreased the mitochondrial transmembrane potential (MTP) dose-dependently in HepG2 cells, suggesting that the compound induced HepG2 cell apoptosis via the mitochondrial pathway. In conclusion, enterocarpam-III inhibited HepG2 and MDA-MB-231 cell proliferation and induced human HepG2 cells to undergo apoptosis via the intrinsic (mitochondrial) pathway and induction of caspase-9 activity. 2015-06-16T07:47:17Z 2015-06-16T07:47:17Z 2015-01-01 Article 15137368 2-s2.0-84928534379 10.7314/APJCP.2015.16.5.1833 http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84928534379&origin=inward http://cmuir.cmu.ac.th/handle/6653943832/38468 Asian Pacific Organization for Cancer Prevention |
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Cancer Research Oncology Epidemiology Public Health, Environmental and Occupational Health Banjerdpongchai,R. Wudtiwai,B. Pompimon,W. Enterocarpam-III induces human liver and breast cancer cell apoptosis via mitochondrial and caspase-9 activation |
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An aristolactam-type alkaloid, isolated from Orophea enterocarpa, is enterocarpam-III (10-amino-2,3,4,6-tetramethoxyphenanthrene-1-carboxylic acid lactam). It is cytotoxic to various human and murine cancer cell lines; however, the molecular mechanisms remain unclear. The aims of this study were to investigate cytotoxic effects on and mechanism (s) of human cancer cell death in human hepatocellular carcinoma HepG2 and human invasive breast cancer MDA-MB-231 cells compared to normal murine fibroblast NIH3T3 cells. Cell viability was determined by MTT assay to determine IC<inf>10</inf>, IC<inf>20</inf> and IC<inf>50</inf> levels, reactive oxygen species (ROS) production with 2',7'-dichlorohydrofluorescein diacetate and the caspase-3, -8 and -9 activities using specific chromogenic (p-nitroaniline) tetrapeptide substrates, viz., DEVD-NA, IETD-NA and LEHD-NA and employing a microplate reader. Mitochondrial transmembrane potential (MTP) was measured by staining with 3, 3'-dihexyloxacarbocyanine iodide (DiOC<inf>6</inf>) and using flow cytometry. The compound was cytotoxic to HepG2 and MDA-MB-231 cells with the IC<inf>50</inf> levels of 26.0±4.45 and 51.3±2.05 μM, respectively. For murine normal fibroblast NIH3T3 cells, the IC<inf>50</inf> concentration was 81.3±10.1 μM. ROS production was reduced in a dose-response manner in HepG2 cells. The caspase-9 and -3 activities increased in a concentration-dependent manner, whereas caspase-8 activity did not alter, indicating the intrinsic pathway activation. Enterocarpam-III decreased the mitochondrial transmembrane potential (MTP) dose-dependently in HepG2 cells, suggesting that the compound induced HepG2 cell apoptosis via the mitochondrial pathway. In conclusion, enterocarpam-III inhibited HepG2 and MDA-MB-231 cell proliferation and induced human HepG2 cells to undergo apoptosis via the intrinsic (mitochondrial) pathway and induction of caspase-9 activity. |
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Article |
author |
Banjerdpongchai,R. Wudtiwai,B. Pompimon,W. |
author_facet |
Banjerdpongchai,R. Wudtiwai,B. Pompimon,W. |
author_sort |
Banjerdpongchai,R. |
title |
Enterocarpam-III induces human liver and breast cancer cell apoptosis via mitochondrial and caspase-9 activation |
title_short |
Enterocarpam-III induces human liver and breast cancer cell apoptosis via mitochondrial and caspase-9 activation |
title_full |
Enterocarpam-III induces human liver and breast cancer cell apoptosis via mitochondrial and caspase-9 activation |
title_fullStr |
Enterocarpam-III induces human liver and breast cancer cell apoptosis via mitochondrial and caspase-9 activation |
title_full_unstemmed |
Enterocarpam-III induces human liver and breast cancer cell apoptosis via mitochondrial and caspase-9 activation |
title_sort |
enterocarpam-iii induces human liver and breast cancer cell apoptosis via mitochondrial and caspase-9 activation |
publisher |
Asian Pacific Organization for Cancer Prevention |
publishDate |
2015 |
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http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84928534379&origin=inward http://cmuir.cmu.ac.th/handle/6653943832/38468 |
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