Ascorbyl Stearate Promotes Apoptosis Through Intrinsic Mitochondrial Pathway in HeLa Cancer Cells.

Background: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.