Withaferin A Induces Oxidative Stress-Mediated Apoptosis and DNA Damage in Oral Cancer Cells

Hsueh Wei Chang, Ruei Nian Li, Hui Ru Wang, Jing Ru Liu, Jen Yang Tang, Hurng Wern Huang, Yu Hsuan Chan, Ching Yu Yen

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Withaferin A (WFA) is one of the most active steroidal lactones with reactive oxygen species (ROS) modulating effects against several types of cancer. ROS regulation involves selective killing. However, the anticancer and selective killing effects of WFA against oral cancer cells remain unclear. We evaluated whether the killing ability of WFA is selective, and we explored its mechanism against oral cancer cells. An MTS tetrazolium cell proliferation assay confirmed that WFA selectively killed two oral cancer cells (Ca9-22 and CAL 27) rather than normal oral cells (HGF-1). WFA also induced apoptosis of Ca9-22 cells, which was measured by flow cytometry for subG1 percentage, annexin V expression, and pan-caspase activity, as well as western blotting for caspases 1, 8, and 9 activations. Flow cytometry analysis shows that WFA-treated Ca9-22 oral cancer cells induced G2/M cell cycle arrest, ROS production, mitochondrial membrane depolarization, and phosphorylated histone H2A.X (gH2AX)-based DNA damage. Moreover, pretreating Ca9-22 cells with N-acetylcysteine (NAC) rescued WFA-induced selective killing, apoptosis, G2/M arrest, oxidative stress, and DNA damage. We conclude that WFA induced oxidative stress-mediated selective killing of oral cancer cells.

Original languageEnglish
Article number634
JournalFrontiers in Physiology
Volume8
Issue numberSEP
DOIs
Publication statusPublished - Sep 7 2017

Fingerprint

Mouth Neoplasms
DNA Damage
Oxidative Stress
Apoptosis
Reactive Oxygen Species
Flow Cytometry
G2 Phase Cell Cycle Checkpoints
Caspase 1
withaferin A
Caspase 9
Caspase 8
Annexin A5
Acetylcysteine
Mitochondrial Membranes
Lactones
Caspases
Histones
Western Blotting
Cell Proliferation

Keywords

  • Apoptosis
  • N-acetylcysteine
  • Oral cancer
  • Oxidative stress
  • Selective killing
  • Withaferin A

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Withaferin A Induces Oxidative Stress-Mediated Apoptosis and DNA Damage in Oral Cancer Cells. / Chang, Hsueh Wei; Li, Ruei Nian; Wang, Hui Ru; Liu, Jing Ru; Tang, Jen Yang; Huang, Hurng Wern; Chan, Yu Hsuan; Yen, Ching Yu.

In: Frontiers in Physiology, Vol. 8, No. SEP, 634, 07.09.2017.

Research output: Contribution to journalArticle

Chang, Hsueh Wei ; Li, Ruei Nian ; Wang, Hui Ru ; Liu, Jing Ru ; Tang, Jen Yang ; Huang, Hurng Wern ; Chan, Yu Hsuan ; Yen, Ching Yu. / Withaferin A Induces Oxidative Stress-Mediated Apoptosis and DNA Damage in Oral Cancer Cells. In: Frontiers in Physiology. 2017 ; Vol. 8, No. SEP.
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