Formononetin sensitizes glioma cells to doxorubicin through preventing EMT via inhibition of histone deacetylase 5.
Chemoresistance is a major obstacle to successful chemotherapy for glioma. Formononetin is a novel herbal isoflavonoid isolated from Astragalus membranaceus and possesses antitumorigenic properties. In the present study, we investigated the anti-proliferative effects of formononetin on human glioma cells, and further elucidated the molecular mechanism underlying the anti-tumor property. We found that formononetin enhanced doxorubicin cytotoxicity in glioma cells. Combined treatment with formononetin reversed the doxorubicin-induced epithelial-mesenchymal transition (EMT) in tumor cells. Moreover, we found that formononetin treatment significantly decreased the expression of HDAC5. Overexpression of HDAC5 diminished the suppressive effects of formononetin on glioma cell viability. Furthermore, knockdown of HDAC5 by siRNA inhibited the doxorubicin-induced EMT in glioma cells. Taken together, these results demonstrated that formononetin-combined therapy may enhance the therapeutic efficacy of doxorubicin in glioma cells by preventing EMT through inhibition of HDAC5.
Department of Neurosurgery, The Fourth Affiliated Hospital Guangxi Medical University Liuzhou 545005, Guangxi, China.
Quan
Q
Liu
Department of Scientific Research and Education, The Fourth Affiliated Hospital Guangxi Medical University Liuzhou 545005, Guangxi, China.
Yan
Y
Sun
Department of Neurosurgery, The Fourth Affiliated Hospital Guangxi Medical University Liuzhou 545005, Guangxi, China.
Jie-Min
JM
Zheng
Department of Neurosurgery, The Fourth Affiliated Hospital Guangxi Medical University Liuzhou 545005, Guangxi, China.
Xian-Lei
XL
Yan
Department of Neurosurgery, The Fourth Affiliated Hospital Guangxi Medical University Liuzhou 545005, Guangxi, China.
Hong-Mou
HM
Chen
Department of Neurosurgery, The Fourth Affiliated Hospital Guangxi Medical University Liuzhou 545005, Guangxi, China.
Jia-Kang
JK
Chen
Department of Neurosurgery, The Fourth Affiliated Hospital Guangxi Medical University Liuzhou 545005, Guangxi, China.
He-Qing
HQ
Huang
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
D000903:Antibiotics, Antineoplastic; D056572:Histone Deacetylase Inhibitors; D007529:Isoflavones; C007768:formononetin; D004317:Doxorubicin; C404500:HDAC5 protein, human; D006655:Histone Deacetylases
Glioma; HDAC5; combination treatment; epithelial-mesenchymal transition