Int J Oral Biol.  2020 Dec;45(4):169-178. 10.11620/IJOB.2020.45.4.169.

L-ascorbic acid induces apoptosis in human laryngeal epidermoid Hep-2 cells by modulating the nuclear factor kappa-light-chain-enhancer of activated B cells/ mitogen-activated protein kinase/Akt signaling pathway

Affiliations
  • 1Department of Oral Physiology, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of Korea
  • 2Hard Tissue Biointerface Research Center, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of Korea
  • 3Department of Dental Hygiene, School of Health Science, Honam University, Gwangju 62399, Republic of Korea
  • 4School of Biological Sciences and Technology, College of Natural Sciences, Chonnam National University, Gwangju 61186, Republic of Korea

Abstract

L-ascorbic acid (L-AA; vitamin C) induces apoptosis in cancer cells. This study aimed to elucidate the molecular mechanisms of L-AA-induced apoptosis in human laryngeal epidermoid carcinoma Hep-2 cells. L-AA suppressed the viability of Hep-2 cells and induced apoptosis, as shown by the cleavage and condensation of nuclear chromatin and increased number of Annexin V-positive cells. L-AA decreased Bcl-2 protein expression but upregulated Bax protein levels. In addition, cytochrome c release from the mitochondria into the cytosol and activation of caspase-9, -8, and -3 were enhanced by L-AA treatment. Furthermore, apoptosis-inducing factor (AIF) and endonuclease G (EndoG) were translocated into the nucleus during apoptosis of L-AA-treated Hep-2 cells. L-AA effectively inhibited the constitutive nuclear factor-κB (NF-κB) activation and attenuated the nuclear expression of the p65 subunit of NF-κB. Interestingly, L-AA treatment of Hep-2 cells markedly activated Akt and mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase [JNK]) and and LY294002 (Akt inhibitor), SB203580 (p38 inhibitor) or SP600125 (a JNK inhibitor) decreased the levels of Annexin V-positive cells. These results suggested that L-AA induces the apoptosis of Hep-2 cells via the nuclear translocation of AIF and EndoG by modulating the Bcl- 2 family and MAPK/Akt signaling pathways.

Keyword

Apoptosis; Ascorbic acid; Mitogen-activated protein kinase; NF-kappa B; Squamous cell
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