O-Glycoprotein DeGP-4 From Dioscorea esculenta (Lour.) Burkill: Isolation, Structural Characterization, and Potent Anti-Triple-Negative Breast Cancer Activity.

The present study aimed to extract and purify the glycoprotein (DeGP-4) from Dioscorea esculenta (Lour.) Burkill, investigate its antitumor activity and molecular mechanism against MDA-MB-231 and BT-549 breast cancer cell lines. The glycoprotein DeGP-4 was isolated, which contained 48.35% carbohydrates and 50.20% proteins. DeGP-4 was identified as glycoprotein around 23.28 kDa, a purity of 93.20%, and contained 16 different amino acids, in which the Asp and Glu were predominant. The carbohydrate chain composition was predominantly mannose (53.84%), glucose (43.38%), galactose (2.08%), and arabinose (0.99%), and two O-glycosylation sites were identified at positions 94 and 146. DeGP-4 demonstrated potent inhibitory effects on the proliferation of MDA-MB-231 and BT-549 breast cancer cells, with IC50 values of 1.2 and 2.5 µg/mL. The inhibitory effect of DeGP-4 on MDA-MB-231 is better than cisplatin, and the inhibitory effect on BT-549 is comparable to cisplatin. DeGP-4 may suppress tumor cell migration and induced apoptosis by promoting reactive oxygen species (ROS) production and modulating the expression of key apoptotic proteins, including downregulation of Bcl-2 and upregulation of Bax and Caspase-3. Furthermore, in vivo experiments conducted the mouse tumor model, supported by histological and immunohistochemical analyses, confirmed the significant antitumor activity of DeGP-4.