Lack of mitochondrial DNA enhances growth of hepatocellular carcinoma in vitro and in vivo

Anwarul Haque; Manabu Nishikawa; Wei Qian; Masayuki Mashimo; Masaki Hirose; Shuhei Nishiguchi; Masayasu Inoue

doi:10.1016/j.hepres.2006.07.005

Lack of mitochondrial DNA enhances growth of hepatocellular carcinoma in vitro and in vivo

Hepatol Res. 2006 Nov;36(3):209-16. doi: 10.1016/j.hepres.2006.07.005. Epub 2006 Aug 21.

Authors

Anwarul Haque¹, Manabu Nishikawa, Wei Qian, Masayuki Mashimo, Masaki Hirose, Shuhei Nishiguchi, Masayasu Inoue

Affiliation

¹ Department of Biochemistry & Molecular Pathology, Osaka City University Medical School, Osaka 545-8585, Japan.

PMID: 16920399
DOI: 10.1016/j.hepres.2006.07.005

Abstract

To elucidate the role of mitochondrial DNA (mtDNA) in determination of growth of hepatocellular carcinoma, we examined wild-type Hepa1-6 cells and their rho(0) cells with depleted mtDNA in vitro and in vivo. Cultured rho(0) cells grew more rapidly than did wild-type cells. Production of reactive oxygen species (ROS) was higher in wild-type cells than in rho(0) cells. Hypoxia inhibited the growth of wild-type cells more markedly than that of rho(0) cells. Resistance to mitochondrial respiratory inhibitor-induced cell death was stronger in rho(0) cells than in wild-type cells. rho(0) cells subcutaneously inoculated in the hind thigh of mice grew more rapidly and formed larger solid tumors. These findings indicate that lack of mtDNA increases growth of hepatocellular carcinoma by decreasing ROS production and increasing resistance to mitochondrial respiratory inhibition.