High concentrations of L-ascorbic acid (Vitamin C) induces apoptosis in a human cervical cancer cell line (HeLa) through the intrinsic and extrinsic pathways
Although cervical cancer incidence and mortality rates in the developed world have significantly declined over the past 30 years, it is still the second leading cause of death in women aged 19-39 years. Novel developments of chemotherapeutic agents for cervical cancer are important in reducing patient mortality rates. Recent chemotherapeutic developments have begun to manipulate the apoptotic pathway. L-ascorbic acid (Vitamin C) is generally considered an antioxidant at normal physiological levels (60–80 μM), but considered a pro-oxidant at much higher concentrations (> 1 mM). Due to its pro-oxidant effects, in the 1970s L-ascorbic acid underwent clinical trials as an anticancer treatment at high intravenous concentrations (1-2 mM), and presented ambiguous results. In the last 5 years, L-ascorbic acid has been re-investigated in in vitro cancerous cell lines, and has exhibited a selective toxicity in cancerous cells. This investigation aimed to characterize the mechanism of cell death induced by L-ascorbic acid in the human cervical cancer cell line HeLa. We evaluated cell viability over time and caspase-3, −8 and −9 activity after the induction of HeLa cells with L-ascorbic acid (5-10 mM). We hypothesized that high concentrations (5–10 mM) of L-ascorbic acid would induce cell death via an intrinsic apoptotic pathway. The results indicate that 7 mM and 10 mM of L-ascorbic acid induce cell death via an extrinsic and intrinsic apoptotic pathway. Implications of the generation of hydrogen peroxide via L-ascorbic acid are discussed. The findings suggest that L-ascorbic acid could be a potential therapeutic agent for cervical cancer when administered intravenously at high concentrations (7-10 mM).
BIOS 86(3):134-143. 2015
Bradley M. Roberts Danielle R. Fullerton, and Samantha L. Elliott
Copyright Beta Beta Beta Biological Society
Received: June 3, 2014; Accepted: November 20, 2014
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High concentrations of L-ascorbic acid (Vitamin C) induces apoptosis in a human cervical cancer cell line (HeLa) through the intrinsic and extrinsic pathways | BIOS http://www.bioone.org/doi/abs/10.1893/BIOS-D-14-00019.1