Synergistic antitumor effects of polysaccharides and anthocyanins from Lycium ruthenicum Murr. on human colorectal carcinoma LoVo cells and the molecular mechanism

Abstract The antitumor effects of Lycium ruthenicum Murr. polysaccharides (LRPS) and Lycium ruthenicum Murr. anthocyanins (LRAC) were comprehensively investigated in this study. LPRS was obtained by water extraction and alcohol precipitation and further purified using diethylaminoethyl cellulose (DEAE‐Cellulose) and Sephadex G‐75 columns. High‐performance liquid chromatography (HPLC) and Fourier transform‐infrared (FT‐IR) spectroscopy were used to characterize the purified LRPS. The results showed that the purified LRPS contained heteropolysaccharides, mainly composed of arabinose, galactose, and glucose with weight percentage of 41.2%, 33.6%, and 10.8%, respectively. More importantly, LRPS (500 μg/ml) and LRAC (80 μg/ml) failed to impede the proliferation of tumor cells when applied solely (48 h incubation), yet remarkable antineoplastic effects were found once they were applied altogether, since the LoVo cells, a typical human colorectal carcinoma cell line, were significantly inhibited by the mixture of LRPS (150 μg/ml) and LRAC (20 μg/ml) (LRPS&AC) in 24 h. The antineoplastic activity resulted from the combination of both LRPS and LRAC (LRPS&AC), by means of blocking the cell cycle at the G0–G1 phase and inducing LoVo cell apoptosis via reactive oxygen species (ROS)‐dependent pathway. The inhibitory effects of LRPS&AC were specific to the tumor cells, without imposing on the proliferation of normal cells. Western blotting revealed that the antitumor effect was related to the mitochondria‐mediated apoptosis launched by the cross‐action of PI3K/Akt (phosphatidylinositol 3‐kinase/protein kinase B) and JAK2/STAT3 (janus kinase 2/signal transduction and activator of transcription 3) signaling pathways. These findings for the first time reveal the synergistic antitumor effects of LRPS&AC and the related mechanisms, which enable Lycium ruthenicum Murr. to serve as a natural source to develop therapeutic reagents and functional foods with antineoplastic properties.