In vitro and in vivo anti-cancer activity of silymarin on oral cancer

Abstract

Silymarin, a standardized extract from milk thistle fruits has been found to exhibit anti-cancer effects against various cancers. Here, we explored the anti-cancer activity of silymarin and its molecular target in human oral cancer in vitro and in vivo. Silymarin dose-dependently inhibited the proliferation of HSC-4 oral cancer cells and promoted caspase-dependent apoptosis. A human apoptosis protein array kit showed that death receptor 5 may be involved in silymarin-induced apoptosis, which was also shown through western blotting, immunocytochemistry, and reverse transcription-polymerase chain reaction. Silymarin increased cleaved caspase-8 and truncated Bid, leading to accumulation of cytochrome c. In addition, silymarin activated death receptor 5/caspase-8 to induce apoptotic cell death in two other oral cancer cell lines (YD15 and Ca9.22). Silymarin also suppressed tumor growth and volume without any hepatic or renal toxicity in vivo. Taken together, these results provide in vitro and in vivo evidence supporting the anti-cancer effect of silymarin and death receptor 5, and caspase-8 may be essential players in silymarin-mediated apoptosis in oral cancer.

Safety and toxicity of silymarin, the major constituent of milk thistle extract: An updated review

“…Clinically, silymarin showed anti-Parkinson and anti-Alzheimer effects (Ullah & Khan, 2018;Yaghmaei, Azarfar, Dezfulian, & Ebrahim-Habibi, 2014); in addition, anti-inflammatory effects of silymarin was significant in patients with arthritis (Hussain et al, 2009). Anticancer activity of milk thistle was observed in a variety of cancer cells (Agarwal, Agarwal, Ichikawa, Singh, & Aggarwal, 2006;Won et al, 2018). In mice with breast cancer, silymarin had anticancer activity and reduced tumor volume, consequently inhibited tumor growth.…”

Silymarin antiproliferative and apoptotic effects: Insights into its clinical impact in various types of cancer

“…Silymarin also increased the level of cleaved caspase‐8 and truncated Bid in this cell line, resulting in cytochrome c accumulation. A careful analysis of two other oral cancer cell lines (YD15 and Ca9.22) also confirmed the role of death receptor 5/caspase‐8 activation in silymarin‐induced apoptosis (Won et al, ).…”

“…Silymarin is able to inhibit HSC‐4 oral cancer cells proliferation and induce apoptosis in a dose‐dependent manner. An in vitro and in vivo study confirmed the anticancer activity of silymarin in oral cancer (Won et al, ). Through a study performed in salivary gland cancer‐derived MC3 and HN22 cells, it was found that silymarin and silibinin could induce mitochondria‐mediated apoptosis in salivary gland cancer cells, through modulating the proapoptotic protein, in a concentration‐ and time‐dependent manner.…”

The Influence of Lycopene, [6]-Gingerol, and Silymarin on the Apoptosis on U-118MG Glioblastoma Cells In Vitro Model

“…This also confirms the conclusions of our own research on pro-apoptotic properties of [6]-gingerol. Referring to anticancer effects of silymarin, it was noticed that silymarin inhibited oral tumor growth and proliferation of tumor cells [15,36].…”