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Biochem Biophys Res Commun. 2016 Jan 8;469(2):164-70. doi: 10.1016/j.bbrc.2015.11.088. Epub 2015 Nov 23.

Targeting HIF-1α is a prerequisite for cell sensitivity to dichloroacetate (DCA) and metformin.

Author information

1
Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea.
2
KIRAMS Radiation Biobank, Korea Institute of Radiological & Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea.
3
Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea.
4
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.
5
Department of Pharmacology, Seoul National University College of Medicine, 103 Daehangno, Jongno-gu, Seoul 03080, Republic of Korea.
6
Department of Microbiological Engineering, Kon-Kuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea.
7
Department of Food Science & Technology, Seoul Women's University, 621 Hwarangro, Nowon-gu, Seoul 01797, Republic of Korea.
8
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.
9
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.

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.

KEYWORDS:

Cancer metabolism; Dichloroacetate; Glycolytic enzymes; HIF-1α; Metformin

PMID:
26616058
DOI:
10.1016/j.bbrc.2015.11.088
[Indexed for MEDLINE]

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