Decoction of Chinese Herbal Medicine Fuzheng Kang‐Ai Induces Lung Cancer Cell Apoptosis via STAT3/Bcl‐2/Caspase‐3 Pathway

Abstract

Decoction of Chinese herbal medicine (CHM) Fuzheng Kang-Ai (FZKA for short) has been applied as adjuvant treatment strategy in advanced lung cancer patients for decades. We previously showed that FZKA decoction inhibited proliferation of non-small cell lung cancer (NSCLC) cells through activation of AMP-activated protein kinase alpha (AMPKα) signaling pathway, followed by inducing insulin-like growth factor (IGF) binding protein 1 (IGFBP1) and forkhead homeobox type O3a (FOXO3a) proteins, and enhanced the inhibition effect of gefitinib in lung cancer cell growth via inactivating PI3-K/Akt-mediated suppressing of cell surface-associated mucin-1 (MUC1) expression. In this study, we investigated the molecular mechanism by which FZKA decoction affected cell apoptosis in lung cancer cells. Our results show that FZKA induced apoptosis in lung cancer cells. Mechanistically, FZKA activated the caspase-3, PARP, and caspase-9 activities. Both antiapoptotic and proapoptotic proteins from Bcl-2 family were deregulated by FZKA exposure in lung cancer cells. In addition, FZKA reduced protein expressions of signal transducer and activator of transcription 3 (STAT3) and Jun activation domain-binding protein 1 (Jab1), while it concomitantly increased p21 protein. Moreover, the inhibitor of caspase-3 resisted the effect of FZKA on induction of apoptosis. Finally, exogenous overexpression of STAT3 overcame FZKA-inhibited protein expressions of Bcl-2 and myeloid cell leukemia-1 (Mcl-1) as well as Bax and blocked FZKA-induced activities of caspase-3 and caspase-9. Our results show that FZKA decoction promotes lung cancer cell apoptosis through STAT3/Bcl-2/caspase-3 signaling pathways. This study unveils potential novel molecular mechanism by which FZKA controls growth of human lung cancer cells.

FGL1 Regulates Acquired Resistance to Gefitinib by Inhibiting Apoptosis in Non-small Cell Lung Cancer

“…In the current study, we found that knockdown of FGL1 led to clearly enhanced the expression of cleaved caspase 3 and cleaved PARP1, and overcame acquired resistance to ge tinib in NSCLC cells both in vitro and in vivo. Similarly, some studies have shown that activation of STAT3/Bcl-2/caspase 3 signaling can promote apoptosis of NSCLC cells [17,43], and acquired resistance of EGFR-mutated lung cancer to TKI treatment is related to the anti-apoptosis effect of the PARP pathway [44]. Our study unraveled that FGL1 may be involved in the regulation of proliferation and apoptosis in NSCLC cells via modulating the PARP1/caspase pathway.…”

“…Recent evidence suggests that elevated expression of FGL1 can activate the p-STAT/STAT3 pathway to repair injured hepatocytes through inhibiting apoptosis and promoting proliferation [40], and FGL1 exert an antiapoptotic effect on hepatocytes by inhibiting the upregulation of the apoptotic factors of Bax and caspase-9 and enhancing the expression of the antiapoptotic factors Bcl-2 and Bcl-xl [30,35]. It has also been shown that STAT3 signaling is involved in the regeneration and apoptosis of liver injury [33,41,42], and phosphorylated STAT3 regulated the expression of Bax, Bcl-2, and cell cycle-regulatory genes (including c-fos, c-myc, and cyclin), indicating its role in cell proliferation and apoptosis [43]. Although overexpression of FGL1 has been con rmed in several tumors and contributes to poor prognosis [31,[36][37][38]40], FGL1 expression is downregulated in HCC, and loss of FGL1 may lead to the low differentiation of HCC cells [31,36,40].…”

Triptolide exerts an anti-tumor effect on non‑small cell lung cancer cells by inhibiting activation of the IL‑6/STAT3 axis

“…The findings of the present study showed that TP increases the expression of cleaved caspase-3 in NScLc cells. Other authors (13,45) have also stated that inhibition of STATs directly decreases the levels of anti-apoptotic proteins, such as BcL-2 and McL-1, which are known to facilitate tumor cell survival. The results of the current study revealed that TP treatment decreased the expression of BcL-2 and McL-1.…”

Berbamine Inhibits Cell Proliferation, Migration, and Invasion and Induces Cell Apoptosis of A549 Cells Via Regulating C-Maf, PI3K/Akt and MDM2-P53 Pathways

“…Lung cancer is the leading cause of cancer-related death in both men and women around the world. The incidence of lung cancer in China was 73.3 per 100,000, ranking the rst among malignant tumors and is the leading cause of death from cancer in both males (27.21%) and females (21.92%) [1]. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers, and usually diagnosed at an advanced stage with metastasis [2].…”