salubrinal and Uterine-Cervical-Neoplasms

Sarsasapogenin is a sapogenin from the Chinese medical herb Anemarrhena asphodeloides Bunge. In the present study, we revealed that sarsasapogenin exhibited antitumor activity by inducing apoptosis in vitro as determined by Hoechst staining analysis and double staining of Annexin V-FITC/PI. In addition, cell cycle arrest in G2/M phase was observed in sarsasapogenin-treated HeLa cells. Moreover, the results revealed that perturbations in the mitochondrial membrane were associated with the deregulation of the Bax/Bcl-2 ratio which led to the upregulation of cytochrome c, followed by activation of caspases. Meanwhile, treatment of sarsasapogenin also activated Unfolded Protein Response (UPR) signaling pathways and these changes were accompanied by increased expression of CHOP. Salubrinal (Sal), a selective inhibitor of endoplasmic reticulum (ER) stress, partially abrogated the sarsasapogenin-related cell death. Furthermore, sarsasapogenin provoked the generation of reactive oxygen species, while the antioxidant N-acetyl cysteine (NAC) effectively blocked the activation of ER stress and apoptosis, suggesting that sarsasapogenin-induced reactive oxygen species is an early event that triggers ER stress mitochondrial apoptotic pathways. Taken together, the results demonstrate that sarsasapogenin exerts its antitumor activity through both reactive oxygen species (ROS)-mediate mitochondrial dysfunction and ER stress cell death.

Topics: Anemarrhena; Antineoplastic Agents; bcl-2-Associated X Protein; Cell Cycle Checkpoints; Cinnamates; Cytochromes c; Drugs, Chinese Herbal; Endoplasmic Reticulum Stress; Female; G1 Phase Cell Cycle Checkpoints; HeLa Cells; Humans; M Phase Cell Cycle Checkpoints; Mitochondria; Mitochondrial Membranes; Reactive Oxygen Species; Spirostans; Thiourea; Transcription Factor CHOP; Unfolded Protein Response; Uterine Cervical Neoplasms