So-Cheong-Ryong-Tang induces apoptosis through activation of the intrinsic and extrinsic apoptosis pathways, and inhibition of the PI3K/Akt signaling pathway in non-small-cell lung cancer A549 cells

Abstract

BackgroundSo-Cheong-Ryong-Tang (SCRT), a traditional Korean medicine containing eight species of medicinal plant, has been used to treat patients with bronchial asthma and allergic rhinitis for hundreds of years; however, its anti-cancer potential is poorly understood. The present study was designed to evaluate the apoptotic effect of SCRT against human non-small-cell lung cancer (NSCLC) A549 cells.MethodsThe effects of SCRT on cell growth and viability were evaluated by trypan blue dye exclusion and 3-(4, 5-dimethyl-thiazol-2-yl)-2, 5-diphenyl tetrazoliumbromide (MTT) assays, respectively. Apoptosis was detected using 4,6-diamidino-2-phenyllindile (DAPI) staining, agarose gel electrophoresis and flow cytometry. The protein levels were determined by Western blot analysis. Caspase activity was measured using a colorimetric assay.ResultsSCRT treatment resulted in significantly decreased A549 cell growth and viability by induction of apoptosis. SCRT induced the translocation of pro-apoptotic Bax to the mitochondria, mitochondrial membrane permeabilization, cytochrome c release from mitochondria to cytosol, and activated caspase-9 and caspase-3. SCRT also increased death receptor-associated ligands and enhanced the activation of caspase-8 and cleavage of its substrate Bid. However, the pan-caspases inhibitor significantly blocked the SCRT-induced apoptosis, suggesting that it is a caspase-dependent pathway. In addition, SCRT suppressed the phosphorylation of phosphoinositide 3-kinase (PI3K) and Akt, and treatment with a potent inhibitor of PI3K further increased the apoptotic activity of SCRT.ConclusionsThese findings suggest that SCRT may play its anti-cancer actions partly through a suppression of the PI3K/Akt signal pathway in A549 cells, and further in vivo studies on the potential of SCRT for prevention and therapy of NSCLCs are warranted.

Fermented So-Cheong-Ryong-Tang (FCY) induces apoptosis via the activation of caspases and the regulation of MAPK signaling pathways in cancer cells

“…Similarly, the present study found that FCY treatment activated the ERK, p38, and JNK signals and that these expressions were retained during inhibiting the proliferation of AGS cells. In other study for anti-cancer effect of CY, Park et al demonstrated that CY induces the apoptosis through inhibiting the activation of PI3K/AKT signal pathway in A549 human lung carcinoma cells [ 9 ]. However, in present study, the phosphorylation of AKT were not inhibited by FCY in AGS cells.…”

“…The traditional Oriental medicine, So-Cheong-Ryong-Tang (CY), which is also known as Xiao-Qing-Long Tang in China and Sho-Seiryu-To in Japan, is an herbal mixture that has for hundreds of years been used to treat diseases such as allergic rhinitis and asthma in Asian countries [ 5 , 6 ]. Recent evidence indicates that the specific bioactivities of CY include the modulation of gastrointestinal motility [ 7 ], the influencing of gene expression in a rodent model of chronic obstructive pulmonary disease [ 8 ], the regulation cytokines and chemokines on allergic airway inflammation [ 5 ], and the induction of apoptosis in human lung cancer cells [ 9 ]. Additionally, previous studies from our laboratory have suggested that CY has protective effects against hydrogen peroxide-induced hepatotoxicity [ 10 ].…”

So-Cheong-Ryoung-Tang Attenuates Pulmonary Inflammation Induced by Cigarette Smoke in Bronchial Epithelial Cells and Experimental Mice

“…So-Cheong-Ryoung-Tang is a traditional oriental medicine and is known as Xiao-Qing-Long-Tang in China and Sho-Seiryu-To in Japan ( Park et al, 2015 ). It is composed a mixture of eight herbal preparations ( Herba Ephedrae, Radix Paeoniae, Fructus Schisandrae, Tuber Pinelliae, Asiasari Radix, Rhizoma Crudus Zingiberis, Ramulus Cinnamomi , and Radix et Rhizoma Glycyrrhizae ).…”

The anticancer effects of Cucurbitacin I inhibited cell growth of human non‑small cell lung cancer through PI3K/AKT/p70S6K pathway

“…Activation of PI3K/Akt/m TOR signaling pathway is quite common in the genesis of human tumor (5). Such pathway can promote cancer genesis through multiple mechanisms, including gene mutation, decreased expression of tumor suppressor gene PTEN, PI3K mutation or amplification, Akt mutation or amplification, and activation of oncogene receptor (23). Moreover, activation of all pathway components is a factor indicating poor prognosis for numerous tumors, which can induce treatment resistance (20).…”

“…Moreover, activation of all pathway components is a factor indicating poor prognosis for numerous tumors, which can induce treatment resistance (20). Inhibiting such pathway can reverse the resistance, and improve the chemotherapy and radiotherapy effects both in vivo and in vitro (23). Consequently, it is necessary to intensively study the precise mechanism of that pathway (22).…”