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Concentration- and time-dependent effects of two antiepileptic drugs (AEDs), levetiracetam (LEV) and valproic acid (VPA), on proliferation, cytotoxicity and expression of cell cycle regulatory genes were investigated in a human ovarian cancer cell line, OVCAR-3. Cells were cultured with VPA or LEV, at concentrations between 100 μM and 10 mM. Cell proliferation was determined by alamarBlue and BrdU incorporation assays; cytotoxic effects by tetrazolium hydroxide (XTT), acid phosphatase (AP) and lactate dehydrogenase (LDH) assays. Expression of cell cycle regulatory genes was determined by real-time PCR. Exposure to VPA caused a concentration- and time-dependent decrease in cell proliferation (alamarBlue and BrdU incorporation assays), cytotoxic effects above 2.5 mM (XTT and AP assays) and modulated expression of genes primarily responsible for cell cycle arrest in G(1) phase. Cell proliferation was unaffected by exposure to LEV for 24 h and 120 h (alamarBlue assay), but increased when exposed to LEV for 72 h and 168 h, at concentrations from 250 μM to 1 mM. The BrdU incorporation assay showed no effect of LEV on cell proliferation. LEV was cytotoxic at higher concentrations (AP assay), but modulation in expression of cell cycle regulatory genes was not observed. Changes in LDH release were not observed with either AED. In summary, VPA apparently decreased cell proliferation by down-regulating genes responsible for transition from G(1) to S phase and up-regulating genes responsible for G(1) phase arrest, which suggest its potential as an anticancer drug. LEV does not exhibit such action.

Epithelia in the skin, gut and other environmentally exposed organs display a variety of mechanisms to control microbial communities and limit potential pathogenic microbial invasion. Naturally occurring antimicrobial proteins/peptides and their synthetic derivatives (here collectively referred to as AMPs) reinforce the antimicrobial barrier function of epithelial cells. Understanding how these AMPs are functionally regulated may be important for new therapeutic approaches to combat microbial infections. Some AMPs are subject to redox-dependent regulation. This review aims to: (i) explore cysteine-based redox active AMPs in skin and intestine; (ii) discuss casual links between various redox environments of these barrier tissues and the ability of AMPs to control cutaneous and intestinal microbes; (iii) highlight how bacteria, through intrinsic mechanisms, can influence the bactericidal potential of redox-sensitive AMPs.