Induction of apoptosis in human lung carcinoma cells by the water extract of Panax notoginseng is associated with the activation of caspase-3 through downregulation of Akt

Abstract

Abstract. The root of Panax notoginseng is highly valued and commonly used in Oriental medicine. Although recent experimental data have revealed the proapoptotic potency of P. notoginseng extracts, the underlying molecular mechanisms of this apoptotic activity have not yet been studied in detail. In the present study, the effects of the water extract of P. notoginseng (WEPN) on the growth of human lung carcinoma cells were investigated. It was found that the exposure of A549 and NIC-H460 cells to WEPN resulted in growth inhibition and the induction of apoptosis in a dosedependent manner. The WEPN treatment induced the upregulation of pro-apoptotic Bax, downregulation of antiapoptotic Bcl-2 expression and loss of mitochondrial membrane potential (MMP), which was associated with the proteolytic activation of caspases and the concomitant degradation of poly(ADP ribose) polymerase (PARP) protein. However, the caspase-3-specific inhibitor z-DEVD-fmk blocked PARP degradation and increased the survival rate of WEPN-treated cells. Moreover, the activity of Akt was downregulated in WEPN-treated cells and the phosphatidylinositol-3 kinase (PI3K)/Akt inhibitor LY294002 sensitized the cells to WEPN-induced apoptosis through enhancing the activation of caspase-3 and loss of MMP. The results indicated that the major regulators of WEPN-induced apoptosis in human lung carcinoma cells are the Bcl-2 family and caspase-3, which are associated with mitochondrial dysfunction and dephosphorylation of the Akt signaling pathway.

In Vitro Evaluation of Anti-Lung Cancer and Anti-COVID-19 Effects using Fermented Black Color Ginseng Extract

“…A previous study reported that application of P. ginseng extract could induce apoptosis in A549 cells by activating p53 and caspase 3. 26 Changes in the expression of p53 correlated with changes in 2 downstream Bcl2 family proteins; BAX and Bcl2. This observation is in agreement with the transcriptional expression change of p53 in the A549 cell line.…”

Characterization and function of human Ly-6/uPAR molecules

“…Elevated LY-6K is a serologic diagnostic biomarker and therapeutic target for breast cancer, lung and esophageal carcinomas, bladder cancer, and esophageal squamous cell carcinoma (ESCC) (28-31). Induced LY-6K regulates cell growth, invasion, and migration of lung, esophageal, breast, and bladder cancer cell lines (29,30,32). Additionally, LY-6K is an immunotherapeutic target of cancer vaccine therapies because LY-6K stimulates cytotoxic T lymphocytes that have specific cytotoxic activity against ESCC cells that endogenously express LY-6K (33).…”