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LW6, a hypoxia-inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells

SATO, MARIKO ; HIROSE, KATSUMI ; KASHIWAKURA, IKUO ; AOKI, MASAHIKO ; KAWAGUCHI, HIDEO ; HATAYAMA, YOSHIOMI ; AKIMOTO, HIROYOSHI ; NARITA, YUICHIRO ; TAKAI, YOSHIHIRO

Molecular medicine reports, 2015-09, Vol.12 (3), p.3462-3468 [Periódico revisado por pares]

Greece: D.A. Spandidos

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Título:
LW6, a hypoxia-inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells
Autor: SATO, MARIKO ; HIROSE, KATSUMI ; KASHIWAKURA, IKUO ; AOKI, MASAHIKO ; KAWAGUCHI, HIDEO ; HATAYAMA, YOSHIOMI ; AKIMOTO, HIROYOSHI ; NARITA, YUICHIRO ; TAKAI, YOSHIHIRO
Assuntos: A549 ; Acetanilides - pharmacology ; Adamantane - analogs & derivatives ; Adamantane - pharmacology ; Antineoplastic Agents - pharmacology ; Apoptosis ; Biotechnology ; Cancer ; Cancer therapies ; Cell growth ; Cell Hypoxia ; Cell Line, Tumor ; Cell Survival - drug effects ; Chemical inhibitors ; Chemotherapy ; Cytochrome ; Depolarization ; Dosage and administration ; Drug Screening Assays, Antitumor ; Drug therapy ; Electron transport ; Gene expression ; Health aspects ; Humans ; Hypoxia ; Hypoxia-inducible factor 1 ; hypoxia-inducible factor 1 inhibitor ; Hypoxia-Inducible Factor 1, alpha Subunit - genetics ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; Hypoxia-inducible factors ; Kinases ; Laboratories ; Lung cancer ; Membrane potential ; Membrane Potential, Mitochondrial - drug effects ; Membranes ; Mitochondria ; Mitochondria - drug effects ; Neoplasia ; Oncology, Experimental ; Oxidative Stress ; Penicillin ; Proteins ; Radiation therapy ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Rodents ; Transcription ; Transcription factors ; Tumors ; Vascular endothelial growth factor ; VHL protein
É parte de: Molecular medicine reports, 2015-09, Vol.12 (3), p.3462-3468
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SourceType-Scholarly Journals-1
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Descrição: Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes that act upon the adaptation of cancer cells to hypoxia. LW6, an HIF-1 inhibitor, was hypothesized to improve resistance to cancer therapy in hypoxic tumors by inhibiting the accumulation of HIF-1α. A clear anti-tumor effect under low oxygen conditions would indicate that LW6 may be an improved treatment strategy for cancer in hypoxia. In the present study, the HIF-1 inhibition potential of LW6 on the growth and apoptosis of A549 lung cancer cells in association with oxygen availability was evaluated. LW6 was observed to inhibit the expression of HIF-1α induced by hypoxia in A549 cells at 20 mM, independently of the von Hippel-Lindau protein. In addition, at this concentration, LW6 induced hypoxia-selective apoptosis together with a reduction in the mitochondrial membrane potential. The intracellular reactive oxygen species levels increased in LW6-treated hypoxic A549 cells and LW6 induced a hypoxia-selective increase of mitochondrial O2*−. In conclusion, LW6 inhibited the growth of hypoxic A549 cells by affecting the mitochondria. The inhibition of the mitochondrial respiratory chain is suggested as a potentially effective strategy to target apoptosis in cancer cells.
Editor: Greece: D.A. Spandidos
Idioma: Inglês

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LW6, a hypoxia-inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells

SATO, MARIKO ; HIROSE, KATSUMI ; KASHIWAKURA, IKUO ; AOKI, MASAHIKO ; KAWAGUCHI, HIDEO ; HATAYAMA, YOSHIOMI ; AKIMOTO, HIROYOSHI ; NARITA, YUICHIRO ; TAKAI, YOSHIHIRO

Greece: D.A. Spandidos

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