The dietary flavonoid apigenin sensitizes malignant tumor cells to tumor necrosis factor-related apoptosis-inducing ligand

Molecular Cancer Therapeutics
Mano HorinakaToshiyuki Sakai

Abstract

Dietary flavonoid apigenin is expected to have preventive and therapeutic potential against malignant tumors. In this report, we show for the first time that apigenin markedly induces the expression of death receptor 5 (DR5) and synergistically acts with exogenous soluble recombinant human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to induce apoptosis in malignant tumor cells. TRAIL is a promising candidate for cancer therapeutics due to its ability to selectively induce apoptosis in cancer cells. The combined use of apigenin and TRAIL at suboptimal concentrations induces Bcl-2-interacting domain cleavage and the activation of caspases-8, -10, -9, and -3. Furthermore, human recombinant DR5/Fc chimera protein and caspase inhibitors dramatically inhibit apoptosis induced by the combination of apigenin and TRAIL. On the other hand, apigenin-mediated induction of DR5 expression is not observed in normal human peripheral blood mononuclear cells. Moreover, apigenin does not sensitize normal human peripheral blood mononuclear cells to TRAIL-induced apoptosis. These results suggest that this combined treatment with apigenin and TRAIL might be promising as a new therapy against malignant tumors.

References

Oct 28, 1994·Biochemical and Biophysical Research Communications·F SatoT Sakai
Oct 6, 1997·The EMBO Journal·H WalczakC T Rauch
Nov 5, 1997·The Journal of Biological Chemistry·M MacFarlaneE S Alnemri
Nov 5, 1997·Nature Genetics·G S WuW S el-Deiry
Apr 21, 1999·Current Opinion in Cell Biology·A Ashkenazi, V M Dixit
Jul 20, 1999·The Journal of Clinical Investigation·A AshkenaziR H Schwall
Nov 5, 1999·Biochemical and Biophysical Research Communications·H YamadaS Kawanishi
Aug 5, 2000·International Journal of Cancer. Journal International Du Cancer·S CaltagironeM Piantelli
Apr 3, 2001·Nature Medicine·D LawrenceA Ashkenazi
Jun 21, 2001·Journal of Agricultural and Food Chemistry·K H Miean, S Mohamed
Aug 15, 2002·Cancer Letters·Yung-Ming Jeng, Hey-Chi Hsu
Apr 23, 2003·Cancer Letters·Young-Ju JangHyung-Il Kim
Mar 5, 2004·International Journal of Cancer. Journal International Du Cancer·Markus J DechantKlaus-Michael Debatin
Nov 4, 2004·International Journal of Cancer. Journal International Du Cancer·Jaroslaw CzyzDieter F Hülser
Nov 20, 2004·Cancer Gene Therapy·Lidong Zhang, Bingliang Fang
Dec 2, 2004·Nutrition and Cancer·Alberto MonasterioJuan J Martínez-Irujo

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Citations

May 5, 2012·Apoptosis : an International Journal on Programmed Cell Death·Henriette KauntzFrancis Raul
Mar 25, 2011·Environmental Health and Preventive Medicine·Tatsushi YoshidaToshiyuki Sakai
May 23, 2012·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Jun HaQing-Long Guo
Feb 18, 2010·International Journal of Molecular Sciences·Ewelina SzliszkaWojciech Krol
Sep 4, 2012·International Journal of Molecular Sciences·Carmine StolfiGiovanni Monteleone
Dec 4, 2012·International Journal of Molecular Sciences·Ewelina SzliszkaWojciech Król
Jan 1, 2008·International Journal of Molecular Sciences·Ewelina SzliszkaWojciech Król
Jun 28, 2012·International Journal of Oncology·Ewelina SzliszkaWojciech Krol
Dec 11, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Ewelina SzliszkaWojciech Król
May 29, 2010·Cellular and Molecular Life Sciences : CMLS·Guillaume JacqueminOlivier Micheau
Oct 12, 2014·Experimental Eye Research·Rania S SulaimanTimothy W Corson
Nov 1, 2011·Biochimica Et Biophysica Acta·Sarah Frankland-Searby, Sukesh R Bhaumik
Nov 1, 2007·Neoplasia : an International Journal for Oncology Research·Ssu-Chia LinJih-Hwa Guh
Dec 10, 2009·Molecular Aspects of Medicine·Gregory MellierShazib Pervaiz
Nov 26, 2008·Bioorganic & Medicinal Chemistry Letters·Masaaki OzawaAyumi Ohsaki
Aug 12, 2008·Biochemical Pharmacology·Naghma KhanHasan Mukhtar
Feb 15, 2008·Medicinal Research Reviews·Masami Ishibashi, Takashi Ohtsuki
Dec 1, 2012·Molecular Nutrition & Food Research·Émilie C Lefort, Jonathan Blay
Apr 11, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Ewelina Szliszka, Wojciech Krol
Nov 7, 2009·Evidence-based Complementary and Alternative Medicine : ECAM·Ewelina SzliszkaWojciech Krol
Aug 12, 2016·Cellular and Molecular Life Sciences : CMLS·Ufuk Mert, Ahter Dilsad Sanlioglu
Nov 3, 2012·Journal of Agricultural and Food Chemistry·Noor Idayu TahirUmi Salamah Ramli
Jun 8, 2017·International Journal of Molecular Sciences·Joanna BronikowskaWojciech Król
Jan 13, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Monika WaratZenon P Czuba

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