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

ABSTRACT

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 IC ₅₀ 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.