Synergistic apoptotic effects of silibinin in enhancing paclitaxel toxicity in human gastric cancer cell lines

Abstract

Gastric cancer (GC) is the 3rd leading cause of tumor‑associated mortality worldwide. The efficacy of paclitaxel, a frequently used GC chemotherapeutic agent, is hindered due to drug resistance, dose‑induced toxicity and adverse side effects. Silibinin, an active compound of a widely consumed dietary supplement, milk thistle extract, has recently been demonstrated to have strong antitumor efficacy in a human GC cell model. Thus, to enhance the efficacy of GC treatment, the present study evaluated whether silibinin exerted a synergistic therapeutic effect with paclitaxel. It was observed that the combination of silibinin‑paclitaxel was able to trigger cell cycle arrest and apoptosis. The cell cycle arrest assay indicated that silibinin and paclitaxel alone induced a G2/M phase arrest, and the silibinin‑paclitaxel combination strongly inhibited G2/M cells from entering the S phase. The apoptosis assay and western blot analysis of poly‑ADP‑ribose polymerase, pro‑caspase 3 and pro‑caspase 8 demonstrated that silibinin synergized with paclitaxel in promoting SGC‑7901 GC cell apoptosis. Furthermore, upregulation of the ratio of apoptosis regulator Bcl‑2/apoptosis regulator BAX and tumor necrosis factor receptor superfamily member 6 (Fas)/Fas ligand indicated that the silibinin‑paclitaxel combination activated the death receptor‑mediated pathway in SGC‑7901 cells. The results of the present study suggested that silibinin enhanced the therapeutic potential of paclitaxel against human GC SGC‑7901 cells.

Silibinin suppresses epithelial–mesenchymal transition in human non-small cell lung cancer cells by restraining RHBDD1

“…Several publications have demonstrated that silibinin exhibits anti-tumor activity, e.g., in gastric cancer by enhancing paclitaxel toxicity [33] in glioblastoma by inducing apoptosis [34], and in ovarian cancer [35]. Here, we found that silibinin significantly restrains NSCLC cell proliferation, migration, invasion and EMT.…”

Anticancer Potential of Silibinin Loaded Polymeric Nanoparticles against Breast Cancer Cells: Insight into the Apoptotic Genes Targets

“…This effect is incorporated with lower levels of cell division cycle 25C (cdc25C), cyclins (A, B1, D1, D3, and E), and Cdc2/ p34 as well as diminished activity of cyclin-dependent kinases (Errico et al, 2010). SIL is also proved to have the ability to induce program cell death through activation of caspases 3 and 9 along (Zhang et al, 2018). Moreover, SIL treatment decreased the growth and invasiveness of renal cancer 786-O cell while restraining the growth of cell and inducing program cell death in cancer Caki-1 cells through prevention of EGF, ERK1/2 (Raina et al, 2016).…”

Dual Effects of Silibinin on Human Pancreatic Cancer Cells

“…Silibinin-induced apoptosis is associated with the modulation of apoptotic regulatory proteins in human pancreatic cancer cells [13][14][15]. The expression levels of cleaved caspase-3 and LC3B signi cantly increased in MIA PaCa-2 and PANC-1 cells following treatment with 200 µM silibinin (Figs.…”

“…It can inhibit peroxidase and lipoxygenase [9,10]. Previous studies have shown that silibinin exerts anticancer effects on colon cancer, liver cancer, and breast cancer [11][12][13][14]. The role of silibinin in pancreatic cancer cells is as follows.…”