Cancer Stem-Like Phenotype of Mitochondria Dysfunctional Hep3B Hepatocellular Carcinoma Cell Line

Abstract

Mitochondria are major organelles that play various roles in cells, and mitochondrial dysfunction is the main cause of numerous diseases. Mitochondrial dysfunction also occurs in many cancer cells, and these changes are known to affect malignancy. The mitochondria of normal embryonic stem cells (ESCs) exist in an undifferentiated state and do not function properly. We hypothesized that mitochondrial dysfunction in cancer cells caused by the depletion of mitochondrial DNA might be similar to the mitochondrial state of ESCs. We generated mitochondria dysfunctional (ρ0) cells from the Hep3B hepatocellular carcinoma cell line and tested whether these ρ0 cells show cancer stem-like properties, such as self-renewal, chemotherapy resistance, and angiogenesis. Compared with Hep3B cells, the characteristics of each cancer stem-like cell were increased in Hep3B/ρ0 cells. The Hep3B/ρ0 cells formed a continuous and large sphere from a single cell. Additionally, the Hep3B/ρ0 cells showed resistance to the anticancer drug doxorubicin because of the increased expression of ATP-binding cassette Subfamily B Member 1. The Hep3B/ρ0 conditioned medium induced more and thicker blood vessels and increased the mobility and invasiveness of the blood vessel cells. Therefore, our data suggest that mitochondrial dysfunction can transform cancer cells into cancer stem-like cells.

The pharmacology activities of Angelica keiskei Koidzumi and its efficacy and safety in humans

“…Hep3B cell is derived from hepatocellular carcinoma cell lines and NIH3T3 cell line was derived from mouse embryonic fibroblasts and progressed until pre-birth [ 107 , 108 ]. Hep3B cells and NIH3T3 cells were used in in vitro anti-cancer assays [ 109 , 110 ].…”

Mitochondrial DNA-targeted therapy: A novel approach to combat cancer

“…Han et al. ( Han et al., 2021 ) found an increase in stemness-associated genes, such as OCT4, NANOG, and SOX2, after the depletion of mtDNA in Hep3B/rho0 cells, causing the obtaining and maintaining of cancer stem-like properties. And Lee et al.…”

Recent progress in understanding mitokines as diagnostic and therapeutic targets in hepatocellular carcinoma

“…These organelles are closely related to the pathogenesis of liver failure, and possible pathways of action have been proposed. These include ATP depletion due to inhibition of the respiratory chain, oxidative stress, inhibition of fatty acid oxidation, and mitochondrial permeability transition, leading to apoptosis or necrosis of hepatocytes[ 28 , 29 ]. However, the exact mechanism of action has not been fully elucidated.…”