Hydroxysafflor yellow A inhibits the proliferation, migration, and invasion of colorectal cancer cells through the PPARγ/PTEN/Akt signaling pathway

Abstract

ABSTRACT The natural compound Hydroxysafflor yellow A (HSYA) has been demonstrated to exert anti-cancer effect on multiple cancers. This study aimed to clarify the role of HSYA in inhibiting colorectal cancer (CRC) in vitro and the underlying mechanisms. Different concentrations of HSYA (0, 25, 50, and 100 μM) was exposed to HCT116 CRC cells, then cell proliferation, apoptosis, migration, and invasion were estimated by colony formation assay, TUNEL staining, wound-healing, and transwell assays, respectively. Western blotting assay was utilized to observe the expression of proteins involved in cell apoptosis, migration, and peroxisome proliferator-activated receptor γ (PPARγ)/PTEN/Akt signaling, including PCNA, Bax, Bcl-2, cleaved-caspase3, E-cadherin, N-cadherin, vimentin, PPARγ, and phosphorylated (p)-Akt. HCT116 cells that treated with 100 μM HSYA were also pre-treated with PPARγ antagonist, GW9662, or knockdown with PPARγ using short hairpin (sh)-RNA, to down-regulate PPARγ expression. Then, the above functional analysis was repeated. Results demonstrated that HSYA (25, 50 and 100 μM) significantly reduced HCT116 cell viability, but had no effect on the cell viability of human normal intestinal epithelial cell HIEC. HSYA also inhibited colony formation, migration, and invasion but promoted apoptosis of HCT116 cell in a concentration-dependent manner. Besides, the PPARγ/PTEN/Akt signaling was activated upon HSYA treatment. Finally, GW9662 and PPARγ knockdown blocked all the effects of HSYA on HCT116 cells. In conclusion, HSYA could exhibit anti-cancer effect on CRC via activating PPARγ/PTEN/Akt signaling, thereby inhibiting cells proliferation, migration, and invasion in vitro.