title: Ascorbyl Stearate Promotes Apoptosis Through Intrinsic Mitochondrial Pathway in HeLa Cancer Cells.
abstract: Ascorbic acid is proposed to have antitumor potential against certain cancer types but has the limitation of requiring high doses for treating cancer. Ascorbyl stearate (ASC-S) is a fatty acid ester derivative of ascorbic acid with comparable potent apoptotic activity. The present study was aimed at understanding the pathway involved in apoptotic activity of ASC-S in cervical cancer cells.
  
  
  
  The effect of ASC-S on reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) was studied in HeLa cells. Furthermore, the dose-dependent effect of ASC-S on release of cytochrome c, pro-caspase-9, caspase-3, BH3 interacting-domain death agonist (BID), truncated BH3 interacting-domain death agonist (t-BID), FAS ligand (FASL) and transcription factors nuclear factor-kappa B (NF-ĸB), nuclear factor of activated T-cells (NFAT) and activator protein-1 (AP1) were studied in HeLa cells.
  
  
  
  Treatment of HeLa cells with ASC-S significantly increased the MMP. The modulation of MMP resulted in cleavage of BID, expression of FAS, cleavage of pro-caspase-9 and release of cytochrome c into cytosol. In addition, ASC-S treatment resulted in deregulation of transcription factors NF-ĸB, NFAT and AP1, which play an important role in the development of inflammation and cancer.
  
  
  
  Our data, for the first time, suggest that ASC-S has an apoptotic effect against HeLa cells by inducing change in mitochondrial membrane permeability, cytochrome c release and subsequent activation of caspase-3 and NF-ĸB.
authors.affiliation: Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysore, India.
authors.forename: Shirish D
authors.initials: SD
authors.lastname: Mane
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, India.
authors.forename: Maikho
authors.initials: M
authors.lastname: Thoh
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Sharma
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, India.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Sandur
authors.affiliation: Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysore, India akhilnaidu@gmail.com.
authors.forename: K Akhilender
authors.initials: KA
authors.lastname: Naidu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D014157:Transcription Factors; C036225:ascorbyl monostearate; D020782:Matrix Metalloproteinases; D001205:Ascorbic Acid
keywords: Ascorbyl stearate; HeLa cancer cells; apoptosis; extrinsic pathway; intrinsic pathway; mitochondrial membrane potential; reactive oxygen species