The objective of this research was
to investigate the effects of Lactobacillus acidophilus CICC 6074 S-layer protein
on the viability, adhesion, cell cycle, and apoptosis of human colon
cancer HT-29 cells and to explore their molecular mechanism of tumor
suppression. The S-layer protein at doses of 0, 25, 50, and 100 mg/L
significantly suppressed the proliferation of HT-29 cells. The S-layer
protein exerts its cytotoxic activities against colon cancer HT-29
cells by arresting the cell cycle in the G1 phase through upregulating
the expression of p53, p21, and p16 and downregulating the expression
of CDK1 (cyclin-dependent kinases) and cyclin B. Morphological changes
were further observed by transmission electron microscopy, and the
cells treated with the S-layer protein showed obvious characteristic
changes of apoptosis including chromatin condensation, nuclear fragmentation,
vacuoles, and so on. Furthermore, our mechanism studies indicated
that the S-layer protein may induce HT-29 cell apoptosis through the
death receptor apoptotic pathway and mitochondrial pathway and impede
cell invasion by inhibiting the synthesis of the PI3K/AKT pathway
and FasL. These results demonstrated that the L. acidophilus CICC 6074 S-layer protein may be a potential anticarcinogenic agent.