Abstract
Saponins are natural compounds and possess the most promising anti-cancer function. Here, a saponin gleditsia saponin C (GSC), extracted from gleditsiae fructus abnormalis, could induce apoptosis of lung tumor cell line A549 via caspase dependent cascade and this effect could be prevented by the caspase inhibitors. In addition, GSC induced cell death companied with an increase ratio of Bax:Bcl-2 and inhibition of ERK and Akt signaling pathways. Meanwhile, GSC suppressed TNFα inducing NF-κB activation and increased the susceptibility of lung cancer cell to TNFα induced apoptosis. Furthermore, on mouse xenograft model, GSC significantly suppressed tumor growth and induced cancer cell apoptosis, which validated the anti-tumor effect of GSC. Based on these results, GSC might be a promising drug candidate of anti-lung cancer for its potential clinical applications.
Highlights
Lung cancer is characterized by un-controlled cell growth in lung tissues
The membranes were blocked with 5% non-fatted milk, washed four times with Tris-buffered saline plus Tween (TBS-T, 15 min each time), and incubated with the following primary antibodies: p-c-Jun N-terminal kinase (JNK), JNK, p-Akt (Ser 473), Akt, p-PI3K, PI3K, Fas, cleaved caspase-3, 7, 8, 9, p-IκB kinase (IKK)-β, IKK-β, p-IκBα, IκBα, NFκB p65, p-extracellular signal-regulated kinase (ERK), ERK, p-p38, p38, poly(ADP-ribose) polymerase (PARP), Bad, Bax, Bcl-xl, Bcl-2, Lamin B, GAPDH (Cell Signaling Technology, Beverly, MA, United States)
gleditsia saponin C (GSC) could inhibit the growth of lung cancer cells significantly while showed on obvious toxicity on normal lung cells
Summary
Lung cancer is characterized by un-controlled cell growth in lung tissues. Apoptosis is mediated by a number of molecules that either inhibit (including Bcl-xl, Bcl, and the IAP family of proteins) or induce (such as Bak, Bad, and caspases) cell death (Aouacheria et al, 2017). Apoptotic pathways are hot targets of cancer therapies and related drug development. We investigated the effects of GSC on cell viability as well as apoptosis induction in human lung cancer cell lines. The MAPK cascade, caspase activation, and NF-κB pathway are all found to be involved in apoptosis induction mechanisms of GSC. GSC could increase the susceptibility of cancer cells to TNFα-triggered cell death via inhibiting NF-κB activity. Anti-apoptosis effect of GSC was validated on xenograft tumor animal model, which further proved its potentiality of anti-lung cancer drug development
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