Target Identification-Based Analysis of Mechanism of Betulinic Acid-Induced Cells Apoptosis of Cervical Cancer SiHa

Abstract

Cervical cancer is the fourth most common female malignancy with high morbidity and mortality, which urgently needs novel anti-cancer drugs. Accumulating investigations have focused on the antitumor activity of betulinic acid (BA), which is a natural compound with low toxicity and high efficiency. Although the effect of BA on SiHa cells is obvious, the specific mechanism is seldom studied. Target identification is an important part of research on the internal mechanism of action. In this current study, an integrated method based on literature collection, target prediction, enrichment analysis, network analysis, and western blotting experiments was performed to identify the potential key targets of BA-induced apoptosis. Then, combined with the identified potential key targets, the specific mechanism of BA-induced cervical cancer SiHa cells apoptosis was elucidated. Our present study demonstrated that BA significantly reduces the viability of cervical cancer SiHa cells in a dose- and time-dependent manner. In addition, 8 potential key targets (AKT1, CASP8, LMNA, TNF, BCL2, CASP3, PARP1, and XIAP) were obtained through our integrated target identification method. Meanwhile, western blotting showed that within a certain concentration range, the expression of cleaved-caspase 3, cleaved-PARP, and cytochrome c increased with the BA concentration, while XIAP was almost unchanged. Therefore, the effect of BA on cervical cancer is noticeable. BA-induced SiHa cells apoptosis is a multi-molecule coordinated process. In this process, BA is not only a participant in either the extrinsic or intrinsic pathways, but also a regulator of apoptosis effector molecules of the CASP3/PARP1 axis.