Wharton's Jelly Mesenchymal Stem Cells Derived Secretome Inhibits Colorectal Cancer Cell Growth Via Suppressing Mitophagy

Abstract

The anti-cancer effects of Wharton's jelly mesenchymal stem cells (WJSC)-derived secretome (WJSC-S) have been demonstrated in previous studies. However, the anti-cancer mechanism of WJSC-S in tumor suppression remains largely elusive. This study investigated the cytotoxic impacts of WJSC-S by evaluating autophagy and mitophagy on a colon carcinoma cell line (HT-29 cells). The HT-29 cells were treated with 100 µg/mL WJSC-S with or without mitochondrial division inhibitor-1 (Mdivi-1) for 24 hours. MTT test and DAPI staining had used to determine the impacts of WJSC-S on the viability and apoptosis rates of the cells. Mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS) formation, and expression of autophagy and mitophagy-related genes (Parkin and PINK1) had evaluated. Protein levels of the Parkin, PINK1, and LC3-II/LC3-I ratio were also evaluated. WJSC-S reduced ΔΨm and survival of the cells while ROS level and apoptosis index significantly increased. WJSC-S raised the expression of Parkin and reduced PINK1 expression in the HT-29 cells. WJSC-S could also decrease the expression of Beclin-1, ATG5, and ATG12 genes and reduce the LC3-II/LC3-I ratio. Mdivi-1 could enhance WJSC-S impacts on the cancer cells. These findings show that WJSC-S prevents the proliferation of the HT-29 cells and elevates HT-29 cell death by suppressing the mitophagy process.

Keywords:
secretome; mesenchymal stem cells; colon cancer; autophagy; mitophagy

HIGHLIGHTS

WJSC-S suppresses mitophagy in colon cancer cells

WJSC-S suppresses autophagy in colon cancer cells

WJSC-S reduces ΔΨm and survival of the colon cancer cells

WJSC-S increases ROS level and apoptosis index in colon cancer cells