α-bisabolol enhances radiotherapy-induced apoptosis in endometrial cancer cells by reducing the effect of XIAP on inhibiting caspase-3

Abstract

Endometrial cancer (EC) is one of the most common cancers in females. Although the diagnosis and treatment in early stages can greatly improve the survival rate of patients, the advanced EC still is lethal. Radiotherapy is widely used against EC, and it is a great challenge to find an effective way to overcome the resistance of EC during radiotherapy. α-bisabolol is a promising drug, which has already exhibited its anti-tumor effect in some malignancies. Here we reported that α-bisabolol could inhibit the proliferation of EC cells. It is also shown that their abilities of migration and invasion were effectively reduced by α-bisabolol. Furthermore, our results also demonstrated that α-bisabolol could improve sensitivity of EC cells in radiotherapy and further inhibited the growth of EC cells. By Western blot, we found the expression of matrix metalloproteinases-9 (MMP-9) and cyclin E were significantly decreased, which indicated that EC cells can be further suppressed by using α-bisabolol and radiotherapy. It is also demonstrated in our study that the rate of apoptotic cells is markedly increased in EC by using these two treatments. The significant decrease in X-linked inhibitor of apoptosis protein (XIAP) and increase in caspase-3 detected in our study suggested that the enhancement of apoptosis is mediated by XIAP/caspase-3 pathway, which was further confirmed by examining the downstream effectors of caspase-3, COX-2, PARP and cleaved PARP. In the present study, we demonstrated that α-bisabolol could enhance the sensitivity of EC cells to radiotherapy, which provide a novel alternative for overcoming radioresistance of EC cells and achieving a better outcome in radiotherapy.

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

“…Exhibited cytotoxic effects and inhibited cell growth [205][206][207][208][209][210][211][212][213][214][215][216]. Induced apoptosis [217].…”

“…Radiotherapy is widely used against endometrial cancer, and α-bisabolol improved the sensitivity of endometrial cancer cells to radiotherapy and further inhibited the growth of endometrial cancer cells [213]. In oral cancer, 5-aminolevulinic (5-ALA) acid is used in photodynamic therapy but exhibits poor penetration of oral tissues due to its high hydrophilicity.…”

Health Benefits, Pharmacological Effects, Molecular Mechanisms, and Therapeutic Potential of α-Bisabolol

“…Therefore, their levels were further assessed revealing a reduced COX-2 and an increased cleaved PARP following α-Bisabolol treatment. There was also a synergistic improvement in the inhibitory outcome on EC cell growth when α-Bisabolol was combined with radiotherapy along with radiosensitivity enhancement[ 59 ].…”

Lemongrass Essential Oil Components with Antimicrobial and Anticancer Activities

“…It induces the permeability of the outer mitochondrial membrane and plays a crucial role during apoptosis [ 147 ]. α-bisabolol-induced damage to lysosomal and mitochondrial membranes via BID resulted in autophagy and regulated cell death, enlightening its modes of action [ 146 , 147 , 148 , 149 ].…”