The partial extract of Chinese remedy, Suan-Zao-Ren-Tang, can enhance the effectiveness of vinorelbine in treating non-small cell lung cancer through amplification of spindle assembly checkpoint activation.
The study methodology involved the fractionation of Suan-Zao-Ren-Tang, specifically its B7E2 partial extract, guided by its bioactivity in the non-small cell lung cancer cell lines A549 and NCI-H460. Examination of components and bioactivity, along with a mechanistic study, were performed on three different preparations of B7E2 and their individual components. The core components responsible for B7E2 activity were identified as senkyunolide-A, -neocnidilide, 3-butylidenephthalide, betulinic acid, and linoleic acid.
The results of this study demonstrated that while B7E2 alone had no cytotoxic effect, its use in combination with vinorelbine significantly increased the rate of cell death in non-small cell lung cancer cells due to a synergistic activity. This was further confirmed by identifying heightened activation of caspase and phosphorylation of Bcl-2 and Bcl-xL, markers of apoptosis. Additionally, this combination treatment lengthened mitotic arrest and substantially activated the spindle assembly checkpoint, as observed by the phosphorylation of BUBR1 and the upregulation of cyclin B1. It also increased the interaction between components of the mitotic checkpoint complex.
