Nepal Saroj, Park Pil-Hoon
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
Biomol Ther (Seoul). 2014 Sep;22(5):384-9. doi: 10.4062/biomolther.2014.021. Epub 2014 Sep 30.
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.
脂联素是一种主要由脂肪组织分泌的脂肪因子，具有多种生物学效应，包括葡萄糖和脂质代谢以及癌细胞凋亡。最近，脂联素也被证明可调节自噬。虽然新出现的证据表明自噬在调节癌细胞增殖和凋亡中发挥作用，但脂联素引起的自噬在癌细胞凋亡中的作用尚未得到研究。在本研究中，我们证明球形脂联素（gAcrp）可诱导人肝癌细胞系（HepG2细胞）和乳腺癌细胞（MCF-7）发生凋亡和自噬，这可通过半胱天冬酶-3活性、Bax、微管相关蛋白轻链3-II（LC3 II）蛋白水平的升高以及自噬体形成来证明。有趣的是，自噬标志物LC3B的基因沉默显著增强了gAcrp在HepG2和MCF-7细胞系中诱导的凋亡，而雷帕霉素（一种mTOR抑制剂）诱导的自噬显著抑制了gAcrp在肝癌细胞HepG2中诱导的凋亡。此外，自噬调节对gAcrp诱导的HepG2细胞中Bax表达产生了类似的影响。这些结果表明，自噬的诱导在脂联素诱导的癌细胞凋亡中起调节作用，因此抑制自噬将是一个新的有前景的靶点，可提高脂联素诱导癌细胞凋亡的效率。
