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Mechanism of HIF-1alpha-dependent suppression of hypoxia-induced apoptosis in squamous cell carcinoma cells.
Cancer Sci. 2005 Jul; 96(7):394-402.CS

Abstract

The transcriptional factor hypoxia-inducible factor-1 (HIF-1) plays an important role in solid tumor cell growth and survival. Overexpression of HIF-1alpha has been demonstrated in many human tumors and predicts a poor response to chemoradiotherapy. We examined the HIF-1alpha-induced survival pathways in human oral squamous cell carcinoma cell (OSCC) lines. The results showed that forced expression of HIF-1alpha suppressed hypoxia-induced apoptosis of OSCC lines by inhibiting cytochrome c release from mitochondria. Overexpression of HIF-1alpha inhibited the generation of reactive oxygen species (ROS), elevation of intracellular Ca(2+) concentration, reduction of mitochondrial membrane potential, and cytosolic accumulation of cytochrome c, which resulted in the inactivation of caspase-9 and caspase-3. In addition, antiapoptotic Bcl-2 and Bcl-X(L) levels were increased and pro-apoptotic Bax and Bak levels were decreased in the HIF-1alpha-overexpressing OSCC line. Overexpression of HIF-1alpha also increased the levels of phosphorylation of Akt and extracellular signal-regulated kinases (ERK). These findings indicate that HIF-1alpha prevents apoptotic cell death through two mechanisms, including inhibition of cytochrome c release and activation of Akt and ERK.

Authors+Show Affiliations

Department of Oral Oncology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku-city, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16053510

Citation

Sasabe, Eri, et al. "Mechanism of HIF-1alpha-dependent Suppression of Hypoxia-induced Apoptosis in Squamous Cell Carcinoma Cells." Cancer Science, vol. 96, no. 7, 2005, pp. 394-402.
Sasabe E, Tatemoto Y, Li D, et al. Mechanism of HIF-1alpha-dependent suppression of hypoxia-induced apoptosis in squamous cell carcinoma cells. Cancer Sci. 2005;96(7):394-402.
Sasabe, E., Tatemoto, Y., Li, D., Yamamoto, T., & Osaki, T. (2005). Mechanism of HIF-1alpha-dependent suppression of hypoxia-induced apoptosis in squamous cell carcinoma cells. Cancer Science, 96(7), 394-402.
Sasabe E, et al. Mechanism of HIF-1alpha-dependent Suppression of Hypoxia-induced Apoptosis in Squamous Cell Carcinoma Cells. Cancer Sci. 2005;96(7):394-402. PubMed PMID: 16053510.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanism of HIF-1alpha-dependent suppression of hypoxia-induced apoptosis in squamous cell carcinoma cells. AU - Sasabe,Eri, AU - Tatemoto,Yukihiro, AU - Li,Dechao, AU - Yamamoto,Tetsuya, AU - Osaki,Tokio, PY - 2005/8/2/pubmed PY - 2005/9/22/medline PY - 2005/8/2/entrez SP - 394 EP - 402 JF - Cancer science JO - Cancer Sci VL - 96 IS - 7 N2 - The transcriptional factor hypoxia-inducible factor-1 (HIF-1) plays an important role in solid tumor cell growth and survival. Overexpression of HIF-1alpha has been demonstrated in many human tumors and predicts a poor response to chemoradiotherapy. We examined the HIF-1alpha-induced survival pathways in human oral squamous cell carcinoma cell (OSCC) lines. The results showed that forced expression of HIF-1alpha suppressed hypoxia-induced apoptosis of OSCC lines by inhibiting cytochrome c release from mitochondria. Overexpression of HIF-1alpha inhibited the generation of reactive oxygen species (ROS), elevation of intracellular Ca(2+) concentration, reduction of mitochondrial membrane potential, and cytosolic accumulation of cytochrome c, which resulted in the inactivation of caspase-9 and caspase-3. In addition, antiapoptotic Bcl-2 and Bcl-X(L) levels were increased and pro-apoptotic Bax and Bak levels were decreased in the HIF-1alpha-overexpressing OSCC line. Overexpression of HIF-1alpha also increased the levels of phosphorylation of Akt and extracellular signal-regulated kinases (ERK). These findings indicate that HIF-1alpha prevents apoptotic cell death through two mechanisms, including inhibition of cytochrome c release and activation of Akt and ERK. SN - 1347-9032 UR - https://www.unboundmedicine.com/medline/citation/16053510/Mechanism_of_HIF_1alpha_dependent_suppression_of_hypoxia_induced_apoptosis_in_squamous_cell_carcinoma_cells_ L2 - https://doi.org/10.1111/j.1349-7006.2005.00065.x DB - PRIME DP - Unbound Medicine ER -