Lactobacilli metabolites restore E-cadherin and suppress MMP9 in cervical cancer cells

Cervical cancer is leading cause of cancer death in females worldwide. Vaginal lactobacilli colonizing cervical area are known to play an important role in maintaining cervical physiological conditions to ward away vaginal infections including bacterial vaginosis (BV) and cancer prevention. There are limited studies to study effect of Lactobacilli isolated from different sources on cervical cancer. The objective of the study was to investigate the potential of cell-free culture supernatants (CFCs) or metabolites of twelve well-characterized Lactobacillus species from different microenvironments for their anti-proliferative properties on HPV16 and HPV18 cervical cancer cells and to investigate the mechanisms of anti-proliferative and anti-metastatic activities. Lactobacillus metabolites exerted a dose, strain and cell line-dependent effect on cervical cells as demonstrated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. The metabolites from vaginalis and L. salivarius exhibited the lowest half-maximal inhibitory concentration (IC50) on HeLa (131 and 167 ng/ml) respectively and SiHa (149 and 205 ng/ml) respectively. Lactobacilli demonstrating greater inhibitory effect produced majorly l-lactic acid and hydrogen peroxide (H(2)O(2)). Treatment with lactobacilli CFCs significantly upregulated E- cadherin levels in HeLa (p = 0.0451) and SiHa (p = 0.0051) cells and downregulated matrix metalloproteinase 9 (MMP9) levels in Hela cells (p = 0.0465) as measured by ELISA. Lactobacillus-derived metabolites could be explored as biotherapeutics for the control of HPV infections and cervical cancer.