Bauerenol, a triterpenoid from Indian : Induces reactive oxygen species–mediated P38MAPK activation and apoptosis in human hepatocellular carcinoma (HepG2) cells
The triterpenoid, bauerenol, from Suregada angustifolia (Baill. ex Muell.-Arg.) Airy Shaw (Euphorbiaceae) was screened for anti-cancer property using hepatocellular carcinoma cell line, HepG2. Bauerenol exhibited growth inhibitory and apoptosis inducing potential against HepG2 cancer cells. 3-(4,5-d...
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SAGE Publishing
2017-04-01
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| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428317698387 |
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| author | Perumal Sathish Kumar Madepalli Byrappa Gowdu Viswanathan Muthappan Venkatesan Kedike Balakrishna |
| author_facet | Perumal Sathish Kumar Madepalli Byrappa Gowdu Viswanathan Muthappan Venkatesan Kedike Balakrishna |
| author_sort | Perumal Sathish Kumar |
| collection | DOAJ |
| description | The triterpenoid, bauerenol, from Suregada angustifolia (Baill. ex Muell.-Arg.) Airy Shaw (Euphorbiaceae) was screened for anti-cancer property using hepatocellular carcinoma cell line, HepG2. Bauerenol exhibited growth inhibitory and apoptosis inducing potential against HepG2 cancer cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxic assay revealed that bauerenol treatment significantly reduced the growth of HepG2 cells in a time- and dose-dependent manner with 50% growth inhibitory concentration doses of 45 and 25 µg/mL at 24 and 48 h treatments, respectively. Bauerenol-induced cell death reflected apoptotic morphological features, that is, cell membrane blebbing, vacuolization, chromatin condensation, and nuclear fragmentation. In addition, bauerenol treatment diminished the mitochondrial membrane potential, by inducing the efflux of cytochrome c , downregulating the levels of anti-apoptotic Bcl-2 as well as upregulating the levels of pro-apoptotic Bax, and inducing caspase activation and poly (ADP-ribose) polymerase cleavage. Moreover, bauerenol treatment activates p38MAPK and inactivates the anti-apoptotic kinases Akt and ERK1/2 through the induction of reactive oxygen species. Furthermore, bauerenol-mediated S-phase arrest was associated with downregulation of cell cycle-rate-limiting factor (cyclin D1) and upregulation of cyclin-dependent kinase inhibitor p21 and tumor suppressor p53. Interestingly, pre-treatment of cells with reactive oxygen species inhibitor and p38 inhibitor significantly decreases bauerenol-induced cytotoxicity, Bax upregulation, and p38 activation. This study clearly states that bauerenol induces cell cycle arrest and apoptosis through the reactive oxygen species–dependent p38MAPK activation in HepG2 cancer cells. |
| format | Article |
| id | doaj-art-33bdff40648e4ea48f5ebb5f03980331 |
| institution | Kabale University |
| issn | 1423-0380 |
| language | English |
| publishDate | 2017-04-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-33bdff40648e4ea48f5ebb5f039803312025-08-20T03:29:34ZengSAGE PublishingTumor Biology1423-03802017-04-013910.1177/1010428317698387Bauerenol, a triterpenoid from Indian : Induces reactive oxygen species–mediated P38MAPK activation and apoptosis in human hepatocellular carcinoma (HepG2) cellsPerumal Sathish Kumar0Madepalli Byrappa Gowdu Viswanathan1Muthappan Venkatesan2Kedike Balakrishna3Centre for Research and Development of Siddha-Ayurveda Medicines (CRDSAM), Department of Plant Science, Bharathidasan University, Tiruchirappalli, IndiaCentre for Research and Development of Siddha-Ayurveda Medicines (CRDSAM), Department of Plant Science, Bharathidasan University, Tiruchirappalli, IndiaDepartment of Botany, Sourashtra College, Madurai, IndiaEntomology Research Institute, Loyola College, Chennai, IndiaThe triterpenoid, bauerenol, from Suregada angustifolia (Baill. ex Muell.-Arg.) Airy Shaw (Euphorbiaceae) was screened for anti-cancer property using hepatocellular carcinoma cell line, HepG2. Bauerenol exhibited growth inhibitory and apoptosis inducing potential against HepG2 cancer cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxic assay revealed that bauerenol treatment significantly reduced the growth of HepG2 cells in a time- and dose-dependent manner with 50% growth inhibitory concentration doses of 45 and 25 µg/mL at 24 and 48 h treatments, respectively. Bauerenol-induced cell death reflected apoptotic morphological features, that is, cell membrane blebbing, vacuolization, chromatin condensation, and nuclear fragmentation. In addition, bauerenol treatment diminished the mitochondrial membrane potential, by inducing the efflux of cytochrome c , downregulating the levels of anti-apoptotic Bcl-2 as well as upregulating the levels of pro-apoptotic Bax, and inducing caspase activation and poly (ADP-ribose) polymerase cleavage. Moreover, bauerenol treatment activates p38MAPK and inactivates the anti-apoptotic kinases Akt and ERK1/2 through the induction of reactive oxygen species. Furthermore, bauerenol-mediated S-phase arrest was associated with downregulation of cell cycle-rate-limiting factor (cyclin D1) and upregulation of cyclin-dependent kinase inhibitor p21 and tumor suppressor p53. Interestingly, pre-treatment of cells with reactive oxygen species inhibitor and p38 inhibitor significantly decreases bauerenol-induced cytotoxicity, Bax upregulation, and p38 activation. This study clearly states that bauerenol induces cell cycle arrest and apoptosis through the reactive oxygen species–dependent p38MAPK activation in HepG2 cancer cells.https://doi.org/10.1177/1010428317698387 |
| spellingShingle | Perumal Sathish Kumar Madepalli Byrappa Gowdu Viswanathan Muthappan Venkatesan Kedike Balakrishna Bauerenol, a triterpenoid from Indian : Induces reactive oxygen species–mediated P38MAPK activation and apoptosis in human hepatocellular carcinoma (HepG2) cells Tumor Biology |
| title | Bauerenol, a triterpenoid from Indian : Induces reactive oxygen species–mediated P38MAPK activation and apoptosis in human hepatocellular carcinoma (HepG2) cells |
| title_full | Bauerenol, a triterpenoid from Indian : Induces reactive oxygen species–mediated P38MAPK activation and apoptosis in human hepatocellular carcinoma (HepG2) cells |
| title_fullStr | Bauerenol, a triterpenoid from Indian : Induces reactive oxygen species–mediated P38MAPK activation and apoptosis in human hepatocellular carcinoma (HepG2) cells |
| title_full_unstemmed | Bauerenol, a triterpenoid from Indian : Induces reactive oxygen species–mediated P38MAPK activation and apoptosis in human hepatocellular carcinoma (HepG2) cells |
| title_short | Bauerenol, a triterpenoid from Indian : Induces reactive oxygen species–mediated P38MAPK activation and apoptosis in human hepatocellular carcinoma (HepG2) cells |
| title_sort | bauerenol a triterpenoid from indian induces reactive oxygen species mediated p38mapk activation and apoptosis in human hepatocellular carcinoma hepg2 cells |
| url | https://doi.org/10.1177/1010428317698387 |
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