Strong Synergic Growth Inhibition and Death Induction of Cancer Cells by Astragalus membranaceus and Vaccaria hispanica Extract

SIMPLE SUMMARY: Many anti-cancer drugs were developed from botanicals used in traditional medicine. However, modern anti-cancer therapy is often based on drug combinations that provide synergic anti-cancer effects. The aim of our study was to use costumed activity-based screening of traditionally used botanicals, which were previously screened by us for anti-cancer effects, for synergic anti-cancer combinations. We found a combination of two botanicals with very strong synergic effect on cancer cells. This effect was observed in all tested human cancer cell lines and in primary tumor cells. Our results suggest that the treatment interferes with the cell cycle of cancer cells, causing them to accumulate in the G2 phase of the cell cycle and leading to apoptosis. Further research of this combination may lead to the development of new effective anti-cancer therapies. ABSTRACT: We present here a new, classification-based screening method for anti-cancer botanical combinations. Using this method, we discovered that the combination of Astragalus membranaceus and Vaccaria hispanica (AV) has strong synergic anti-proliferative and killing effects on cancer cells. We showed that AV induces the hyper activation of proliferation and survival pathways (Akt and ERK1/2) and strongly downregulates the cell cycle control proteins p21 and p27. Moreover, FACS analyses revealed that AV induces accumulation of cells in G2/M phase, supported by accumulation of cyclin A. Taken together, our results suggest that AV interferes with the cell cycle in cancer cells, leading to accumulation in G2/M and apoptosis. Further studies are needed to validate the generalizability of the anti-cancer effect of the AV combination, to fully understand its mechanism of action and to evaluate its potential as a new anti-cancer treatment.