title: Targeting HIF-1α is a prerequisite for cell sensitivity to dichloroacetate (DCA) and metformin.
abstract: Recently, targeting deregulated energy metabolism is an emerging strategy for cancer therapy. In the present study, combination of DCA and metformin markedly induced cell death, compared with each drug alone. Furthermore, the expression levels of glycolytic enzymes including HK2, LDHA and ENO1 were downregulated by two drugs. Interestingly, HIF-1α activation markedly suppressed DCA/metformin-induced cell death and recovered the expressions of glycolytic enzymes that were decreased by two drugs. Based on these findings, we propose that targeting HIF-1α is necessary for cancer metabolism targeted therapy.
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea.
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Hong
authors.affiliation: KIRAMS Radiation Biobank, Korea Institute of Radiological & Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea.
authors.forename: Hyeon-Ok
authors.initials: HO
authors.lastname: Jin
authors.affiliation: Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea.
authors.forename: Hyun-Ah
authors.initials: HA
authors.lastname: Kim
authors.affiliation: Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea.
authors.forename: Min-Ki
authors.initials: MK
authors.lastname: Seong
authors.affiliation: Department of Surgery, Breast Cancer Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 13620, Republic of Korea.
authors.forename: Eun-Kyu
authors.initials: EK
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Seoul National University College of Medicine, 103 Daehangno, Jongno-gu, Seoul 03080, Republic of Korea.
authors.forename: Sang-Kyu
authors.initials: SK
authors.lastname: Ye
authors.affiliation: Department of Microbiological Engineering, Kon-Kuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea.
authors.forename: Tae-Boo
authors.initials: TB
authors.lastname: Choe
authors.affiliation: KIRAMS Radiation Biobank, Korea Institute of Radiological & Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea.
authors.forename: Jin Kyung
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Food Science & Technology, Seoul Women's University, 621 Hwarangro, Nowon-gu, Seoul 01797, Republic of Korea.
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea. Electronic address: parkic@kcch.re.kr.
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Park
authors.affiliation: Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea. Electronic address: nohwoo@kcch.re.kr.
authors.forename: Woo Chul
authors.initials: WC
authors.lastname: Noh
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003999:Dichloroacetic Acid / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D061986:MCF-7 Cells; D008687:Metformin / Q000008:administration & dosage*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008687:Metformin; D003999:Dichloroacetic Acid
keywords: Cancer metabolism; Dichloroacetate; Glycolytic enzymes; HIF-1α; Metformin