Capsaicin inhibits HIF-1α accumulation through suppression of mitochondrial respiration in lung cancer cells

Tae-Hee Han; Min Kyung Park; Hiroyuki Nakamura; Hyun Seung Ban

doi:10.1016/j.biopha.2021.112500

Capsaicin inhibits HIF-1α accumulation through suppression of mitochondrial respiration in lung cancer cells

Biomed Pharmacother. 2022 Feb:146:112500. doi: 10.1016/j.biopha.2021.112500. Epub 2021 Dec 7.

Authors

Tae-Hee Han¹, Min Kyung Park², Hiroyuki Nakamura³, Hyun Seung Ban⁴

Affiliations

¹ Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, South Korea; Department of Biomolecular Science, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon 34113, South Korea.
² Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, South Korea.
³ Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, Japan. Electronic address: hiro@res.titech.ac.jp.
⁴ Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, South Korea; Department of Biomolecular Science, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon 34113, South Korea. Electronic address: banhs@kribb.re.kr.

PMID: 34891118
DOI: 10.1016/j.biopha.2021.112500

Abstract

Hypoxia inducible factor (HIF)-1α is an important transcription factor regulating cancer metabolism in hypoxic environment. Capsaicin is known to inhibit hypoxia-induced HIF activity in lung cancer. Hence, in this study we tried to elucidate its inhibitory mechanism of action. In lung cancer cells, including H1299, H23, A549, and H2009 cells, capsaicin inhibited cell growth and HIF activation. Under hypoxic conditions, capsaicin reduced the accumulation of HIF-1α protein and the expression of its target genes, including pyruvate dehydrogenase kinase 1 (PDK1) and glucose transporter 1 (GLUT1), with no effect on overall HIF-1α mRNA levels in the H1299 cells. In addition, capsaicin increased intracellular oxygen levels by suppressing mitochondrial respiration, resulting in a reduction of HIF-1α accumulation. Furthermore, mitochondrial ATP production was reduced by capsaicin through the inhibition of mitochondrial respiration in the H1299, H23, A549, and H2009 cells. These results indicate that capsaicin potentially exhibits anticancer therapeutic effects in lung cancer under hypoxic conditions.

Keywords: Capsaicin; HIF-1α; Hypoxia; Lung cancer; Mitochondrial respiration.

MeSH terms

3-Phosphoinositide-Dependent Protein Kinases / drug effects
Capsaicin / pharmacology*
Cell Hypoxia / physiology
Cell Line, Tumor
Glucose Transporter Type 1 / drug effects
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors*
Lung Neoplasms / pathology*
Mitochondria / drug effects*

Substances

Glucose Transporter Type 1
Hypoxia-Inducible Factor 1, alpha Subunit
SLC2A1 protein, human
3-Phosphoinositide-Dependent Protein Kinases
PDPK1 protein, human
Capsaicin