Oxidative stress triggered by naturally occurring flavone apigenin results in senescence and chemotherapeutic effect in human colorectal cancer cells
Recent studies involving phytochemical polyphenolic compounds have suggested flavones often exert pro-oxidative effect in vitro against wide array of cancer cell lines. The aim of this study was to evaluate the in-vitro pro-oxidative activity of apigenin, a plant based flavone against colorectal can...
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doaj-354cdb602add48ff99a3941b40a9c90a2020-11-25T02:20:19ZengElsevierRedox Biology2213-23172015-08-015153162Oxidative stress triggered by naturally occurring flavone apigenin results in senescence and chemotherapeutic effect in human colorectal cancer cellsKacoli Banerjee0Mahitosh Mandal1School of Medical Science and Technology, Indian Institute of Technology, Kharagpur 721302, IndiaCorresponding author.; School of Medical Science and Technology, Indian Institute of Technology, Kharagpur 721302, IndiaRecent studies involving phytochemical polyphenolic compounds have suggested flavones often exert pro-oxidative effect in vitro against wide array of cancer cell lines. The aim of this study was to evaluate the in-vitro pro-oxidative activity of apigenin, a plant based flavone against colorectal cancer cell lines and investigate cumulative effect on long term exposure. In the present study, treatment of colorectal cell lines HT-29 and HCT-15 with apigenin resulted in anti-proliferative and apoptotic effects characterized by biochemical and morphological changes, including loss of mitochondrial membrane potential which aided in reversing the impaired apoptotic machinery leading to negative implications in cancer pathogenesis. Apigenin induces rapid free radical species production and the level of oxidative damage was assessed by qualitative and quantitative estimation of biochemical markers of oxidative stress. Increased level of mitochondrial superoxide suggested dose dependent mitochondrial oxidative damage which was generated by disruption in anti-apoptotic and pro-apoptotic protein balance. Continuous and persistent oxidative stress induced by apigenin at growth suppressive doses over extended treatment time period was observed to induce senescence which is a natural cellular mechanism to attenuate tumor formation. Senescence phenotype inducted by apigenin was attributed to changes in key molecules involved in p16-Rb and p53 independent p21 signaling pathways. Phosphorylation of retinoblastoma was inhibited and significant up-regulation of p21 led to simultaneous suppression of cyclins D1 and E which indicated the onset of senescence. Pro-oxidative stress induced premature senescence mediated by apigenin makes this treatment regimen a potential chemopreventive strategy and an in vitro model for aging research. Keywords: Apigenin, Oxidative stress, Reactive oxygen species, Pro-oxidation, Senescencehttp://www.sciencedirect.com/science/article/pii/S2213231715000403 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kacoli Banerjee Mahitosh Mandal |
spellingShingle |
Kacoli Banerjee Mahitosh Mandal Oxidative stress triggered by naturally occurring flavone apigenin results in senescence and chemotherapeutic effect in human colorectal cancer cells Redox Biology |
author_facet |
Kacoli Banerjee Mahitosh Mandal |
author_sort |
Kacoli Banerjee |
title |
Oxidative stress triggered by naturally occurring flavone apigenin results in senescence and chemotherapeutic effect in human colorectal cancer cells |
title_short |
Oxidative stress triggered by naturally occurring flavone apigenin results in senescence and chemotherapeutic effect in human colorectal cancer cells |
title_full |
Oxidative stress triggered by naturally occurring flavone apigenin results in senescence and chemotherapeutic effect in human colorectal cancer cells |
title_fullStr |
Oxidative stress triggered by naturally occurring flavone apigenin results in senescence and chemotherapeutic effect in human colorectal cancer cells |
title_full_unstemmed |
Oxidative stress triggered by naturally occurring flavone apigenin results in senescence and chemotherapeutic effect in human colorectal cancer cells |
title_sort |
oxidative stress triggered by naturally occurring flavone apigenin results in senescence and chemotherapeutic effect in human colorectal cancer cells |
publisher |
Elsevier |
series |
Redox Biology |
issn |
2213-2317 |
publishDate |
2015-08-01 |
description |
Recent studies involving phytochemical polyphenolic compounds have suggested flavones often exert pro-oxidative effect in vitro against wide array of cancer cell lines. The aim of this study was to evaluate the in-vitro pro-oxidative activity of apigenin, a plant based flavone against colorectal cancer cell lines and investigate cumulative effect on long term exposure. In the present study, treatment of colorectal cell lines HT-29 and HCT-15 with apigenin resulted in anti-proliferative and apoptotic effects characterized by biochemical and morphological changes, including loss of mitochondrial membrane potential which aided in reversing the impaired apoptotic machinery leading to negative implications in cancer pathogenesis. Apigenin induces rapid free radical species production and the level of oxidative damage was assessed by qualitative and quantitative estimation of biochemical markers of oxidative stress. Increased level of mitochondrial superoxide suggested dose dependent mitochondrial oxidative damage which was generated by disruption in anti-apoptotic and pro-apoptotic protein balance. Continuous and persistent oxidative stress induced by apigenin at growth suppressive doses over extended treatment time period was observed to induce senescence which is a natural cellular mechanism to attenuate tumor formation. Senescence phenotype inducted by apigenin was attributed to changes in key molecules involved in p16-Rb and p53 independent p21 signaling pathways. Phosphorylation of retinoblastoma was inhibited and significant up-regulation of p21 led to simultaneous suppression of cyclins D1 and E which indicated the onset of senescence. Pro-oxidative stress induced premature senescence mediated by apigenin makes this treatment regimen a potential chemopreventive strategy and an in vitro model for aging research. Keywords: Apigenin, Oxidative stress, Reactive oxygen species, Pro-oxidation, Senescence |
url |
http://www.sciencedirect.com/science/article/pii/S2213231715000403 |
work_keys_str_mv |
AT kacolibanerjee oxidativestresstriggeredbynaturallyoccurringflavoneapigeninresultsinsenescenceandchemotherapeuticeffectinhumancolorectalcancercells AT mahitoshmandal oxidativestresstriggeredbynaturallyoccurringflavoneapigeninresultsinsenescenceandchemotherapeuticeffectinhumancolorectalcancercells |
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