Lactic acid is partly responsible of the antiproliferative effect of L. acidophilus over Caco-2 and Ht29 cells

[Background] Several independent studies have addressed the beneficial role of lactic acid bacteria over different cancer types, both in vitro and in vivo. However, and to our knowledge, no molecular study has been performed to understand how this inhibitory effect may take place. [Methods] Different fractions from several lactic acid bacteria and bifidobacteria were obtained in order to test their effect over two well-known epithelial cell lines, Caco-2 and Ht29, using the RTCA device. Effect of this extract over cell cycle and the process of necrosis/apoptosis was checked by flow cytometry. Molecular mechanism of action was elucidated by RNASeq. Results: The most active fraction was obtained from Lactobacillus acidophilus, and RNASeq analysis revealed an activation of several detoxification/xenobiotic pathways in epithelial cells. Nuclear magnetic resonance revealed a quite complex extract with the presence of alanine and lactic acid. Alanine had no effect over proliferation but buffering of the extract suggested that some of the observed inhibitory effect was due to lactic acid. The antiproliferative effect was visible from 300 mg/L lactic acid, and 2,7 g/L were enough to induce complete culture death in Ht29 an Caco-2. [Conclusion] Although it remains to known the role of other compounds in the anti-proliferative effect of the L. acidophilus extract, we have shown for the first time that CaCo-2 and Ht29 cell lines are sensible to lactic acid concentrations lower than those observed for instance in yoghourt (9 g/L), suggesting that carcinogenic cells may be more sensitive to lactic acid than normal cells. Production of lactic acid in the colon is therefore a molecular mechanism of action by which lactic acid bacteria exert their beneficial role in the colon.