Biomol Ther.  2014 Sep;22(5):384-389. 10.4062/biomolther.2014.021.

Regulatory Role of Autophagy in Globular Adiponectin-Induced Apoptosis in Cancer Cells

• Nepal S
• Park PH

• KMID: 2380314
• DOI: http://doi.org/10.4062/biomolther.2014.021

Abstract

Adiponectin, an adipokine predominantly secreted from adipose tissue, exhibits diverse biological responses, including metabolism of glucose and lipid, and apoptosis in cancer cells. Recently, adiponectin has been shown to modulate autophagy as well. While emerging evidence has demonstrated that autophagy plays a role in the modulation of proliferation and apoptosis of cancer cells, the role of autophagy in apoptosis of cancer cell caused by adiponectin has not been explored. In the present study, we demonstrated that globular adiponectin (gAcrp) induces both apoptosis and autophagy in human hepatoma cell line (HepG2 cells) and breast cancer cells (MCF-7), as evidenced by increase in caspase-3 activity, Bax, microtubule-associated protein light chain 3-II (LC3 II) protein levels, and autophagosome formation. Interestingly, gene silencing of LC3B, an autophagy marker, significantly enhanced gAcrp-induced apoptosis in both HepG2 and MCF-7 cell lines, whereas induction of autophagy by rapamycin, an mTOR inhibitor, significantly prevented gAcrp-induced apoptosis in hepatoma cells HepG2. Furthermore, modulation of autophagy produced similar effects on gAcrp-induced Bax expression in HepG2 cells. These results implicate that induction of autophagy plays a regulatory role in adiponectin-induced apoptosis of cancer cells, and thus inhibition of autophagy would be a novel promising target to enhance the efficiency of cancer cell apoptosis by adiponectin.

Keyword

Adiponectin; Apoptosis; Autophagy; Bax; HepG2; MCF-7

MeSH Terms

Adipokines
Adiponectin
Adipose Tissue
Apoptosis*
Autophagy*
Breast Neoplasms
Carcinoma, Hepatocellular
Caspase 3
Cell Line
Gene Silencing
Glucose
Hep G2 Cells
Humans
MCF-7 Cells
Metabolism
Sirolimus
Adipokines
Adiponectin
Caspase 3
Glucose
Sirolimus