Apigenin sensitizes prostate cancer cells to Apo2L/TRAIL by targeting adenine nucleotide translocase-2.

Apo2 ligand (Apo2L)/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent. Recombinant human Apo2L/TRAIL has been under clinical trials, whereas various kinds of malignant tumors have resistance to Apo2L/TRAIL. We and others have shown that several a...

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Autores principales:	Masakatsu Oishi, Yosuke Iizumi, Tomoyuki Taniguchi, Wakana Goi, Tsuneharu Miki, Toshiyuki Sakai
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c8968cb76c134178b18d36c1d69487bf
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spelling	oai:doaj.org-article:c8968cb76c134178b18d36c1d69487bf2021-11-18T07:57:06ZApigenin sensitizes prostate cancer cells to Apo2L/TRAIL by targeting adenine nucleotide translocase-2.1932-620310.1371/journal.pone.0055922https://doaj.org/article/c8968cb76c134178b18d36c1d69487bf2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23431365/?tool=EBIhttps://doaj.org/toc/1932-6203Apo2 ligand (Apo2L)/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent. Recombinant human Apo2L/TRAIL has been under clinical trials, whereas various kinds of malignant tumors have resistance to Apo2L/TRAIL. We and others have shown that several anticancer agents and flavonoids overcome resistance to Apo2L/TRAIL by upregulating death receptor 5 (DR5) in malignant tumor cells. However, the mechanisms by which these compounds induce DR5 expression remain unknown. Here we show that the dietary flavonoid apigenin binds and inhibits adenine nucleotide translocase-2 (ANT2), resulting in enhancement of Apo2L/TRAIL-induced apoptosis by upregulation of DR5. Apigenin and genistein, which are major flavonoids, enhanced Apo2L/TRAIL-induced apoptosis in cancer cells. Apigenin induced DR5 expression, but genistein did not. Using our method identifying the direct targets of flavonoids, we compared the binding proteins of apigenin with those of genistein. We discovered that ANT2 was a target of apigenin, but not genistein. Similarly to apigenin, knockdown of ANT2 enhanced Apo2L/TRAIL-induced apoptosis by upregulating DR5 expression at the post-transcriptional level. Moreover, silencing of ANT2 attenuated the enhancement of Apo2L/TRAIL-induced apoptosis by apigenin. These results suggest that apigenin upregulates DR5 and enhances Apo2L/TRAIL-induced apoptosis by binding and inhibiting ANT2. We propose that ANT2 inhibitors may contribute to Apo2L/TRAIL therapy.Masakatsu OishiYosuke IizumiTomoyuki TaniguchiWakana GoiTsuneharu MikiToshiyuki SakaiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e55922 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Masakatsu Oishi Yosuke Iizumi Tomoyuki Taniguchi Wakana Goi Tsuneharu Miki Toshiyuki Sakai Apigenin sensitizes prostate cancer cells to Apo2L/TRAIL by targeting adenine nucleotide translocase-2.
description	Apo2 ligand (Apo2L)/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent. Recombinant human Apo2L/TRAIL has been under clinical trials, whereas various kinds of malignant tumors have resistance to Apo2L/TRAIL. We and others have shown that several anticancer agents and flavonoids overcome resistance to Apo2L/TRAIL by upregulating death receptor 5 (DR5) in malignant tumor cells. However, the mechanisms by which these compounds induce DR5 expression remain unknown. Here we show that the dietary flavonoid apigenin binds and inhibits adenine nucleotide translocase-2 (ANT2), resulting in enhancement of Apo2L/TRAIL-induced apoptosis by upregulation of DR5. Apigenin and genistein, which are major flavonoids, enhanced Apo2L/TRAIL-induced apoptosis in cancer cells. Apigenin induced DR5 expression, but genistein did not. Using our method identifying the direct targets of flavonoids, we compared the binding proteins of apigenin with those of genistein. We discovered that ANT2 was a target of apigenin, but not genistein. Similarly to apigenin, knockdown of ANT2 enhanced Apo2L/TRAIL-induced apoptosis by upregulating DR5 expression at the post-transcriptional level. Moreover, silencing of ANT2 attenuated the enhancement of Apo2L/TRAIL-induced apoptosis by apigenin. These results suggest that apigenin upregulates DR5 and enhances Apo2L/TRAIL-induced apoptosis by binding and inhibiting ANT2. We propose that ANT2 inhibitors may contribute to Apo2L/TRAIL therapy.
format	article
author	Masakatsu Oishi Yosuke Iizumi Tomoyuki Taniguchi Wakana Goi Tsuneharu Miki Toshiyuki Sakai
author_facet	Masakatsu Oishi Yosuke Iizumi Tomoyuki Taniguchi Wakana Goi Tsuneharu Miki Toshiyuki Sakai
author_sort	Masakatsu Oishi
title	Apigenin sensitizes prostate cancer cells to Apo2L/TRAIL by targeting adenine nucleotide translocase-2.
title_short	Apigenin sensitizes prostate cancer cells to Apo2L/TRAIL by targeting adenine nucleotide translocase-2.
title_full	Apigenin sensitizes prostate cancer cells to Apo2L/TRAIL by targeting adenine nucleotide translocase-2.
title_fullStr	Apigenin sensitizes prostate cancer cells to Apo2L/TRAIL by targeting adenine nucleotide translocase-2.
title_full_unstemmed	Apigenin sensitizes prostate cancer cells to Apo2L/TRAIL by targeting adenine nucleotide translocase-2.
title_sort	apigenin sensitizes prostate cancer cells to apo2l/trail by targeting adenine nucleotide translocase-2.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/c8968cb76c134178b18d36c1d69487bf
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_version_	1718422756517740544

Apigenin sensitizes prostate cancer cells to Apo2L/TRAIL by targeting adenine nucleotide translocase-2.

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