Anti-Proliferative and Anti-Metastatic Effects of Ethanol Extract from Cajanus cajan (L.) Millsp. Roots and its Sub-Fractions in Oral Squamous Cell Carcinoma

Abstract

Cajanus cajan (L.) Millsp., known as pigeon pea, C. cajan (L.) Millsp. roots (CR) contain daidzein, genistein, and cajanol which have numerous health benefits. The aim of this study was to investigate the anti-proliferative and anti-metastatic effects of sub-fractions (EECRpw, EECRp25, EECRp50, EECRp70, and EECRp95) containing 95% ethanol extract from CR (EECR95) in oral squamous cell carcinoma cells (SCC25). We found that the sub-fraction (EECRp70) significantly inhibited cell proliferation, and down-regulated secretion of matrix metalloproteinase-2 and vascular endothelial growth factor-2 in a dose-dependent manner, and the mechanisms were related to down-regulated iNOS/COX-2/NF-ĸB signaling pathways. Moreover, EECRp70 in combination with a cancer chemotherapeutic agent (cisplatin or taxol) also blocked cell proliferation, arrested cell cycle in subG1 phase, inhibited intracellular production of reactive oxygen species, and reduced migration and invasion of SCC25 cells. Furthermore, our results demonstrate that EECRp70 inhibits proliferation and metastatic, which is related to the relatively high uptake of genistein of EECRp70 (2.71%) in SCC25 cells for 12 h. In addition, EECRp70 contains abundant flavonoids such as genistein and cajanol. Thus, we suggest that the study supports the anecdotal use of CR in herbal medicine and functional food.