| There is a common agreement on the important role of the gastrointestinal microbiota in the
etiology of cancer. Benign probiotic yeast strains are able to ameliorate intestinal microbiota
and regulate the host metabolism, physiology, and immune system through antiinflammatory,
antiproliferative, and anticancer effects.We hypothesized that Pichia kudriavzevii
AS-12 secretion metabolites possess anticancer activity on human colorectal cancer cells (HT-
29, Caco-2) via inhibiting growth and inducing apoptosis. This study aimed to assess the
anticancer effect of P. kudriavzevii AS-12 secretion metabolites and the underlyingmechanisms.
The cytotoxicity evaluations were performed via 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium
bromide assay; 4′,6-diamidino-2-phenylindole staining; and FACS-flow cytometry
tests. Also, the effects of P. kudriavzevii AS-12 secretionmetabolites on the expression level of 6
important genes (BAD, Bcl-2, Caspase-3, Caspase-8, Caspase-9 and Fas-R) involved in the
extrinsic and intrinsic apoptosis pathwayswere studied by real-time polymerase chain reaction
method. P. kudriavzevii AS-12 secretion metabolites showed significant (P < .0001) cytotoxic
effects on HT-29 cells (57.5%) and Caco-2 (32.5%) compared to KDR/293 normal cells (25%).
Moreover, the cytotoxic effects of examined yeast supernatant on HT-29 cells were comparable
with 5-fluorouracil, as a positive control (57.5% versus 62.2% respectively). Flow cytometric
results showed that the induction of apoptosis is themainmechanismof the anticancer effects. |