Inhibition of IAP’s and activation of p53 leads to caspase-dependent apoptosis in gastric cancer cells treated with Scutellarein

Abstract

Gastric cancer is the fifth most common cancer and the third leading cause of cancer deaths worldwide. South Korea is in first place with 9,180 death alone attributed to gastric cancer in 2013. Plenty of literature suggests the evasion of apoptosis is implicated in neurodegeneration, autoimmune diseases, and tumors development due to dysregulation in the apoptotic mechanism. Reduced apoptosis or its resistance in cancer cells plays a significant role in carcinogenesis. It’s imperative to understand apoptosis, which provides the basis for novel targeted therapies that can induce cancer cell death or sensitize them to cytotoxic agents by regulating key factors like IAPs, MDM2, p53, caspases and much more. Studies have demonstrated that Scutellarein have the ability to inhibit several cancer cells by inducing apoptosis with both: Scutellarein monomers as well as scutellarein containing flavonoids. MTT results revealed that scutellarein inhibited cell viability in both dose and time dependent manner. Flow cytometry and western blot analysis showed that scutellarein induces apoptosis in both AGS and SNU-484 human gastric cancer cells and G2/M phase cell cycle arrest in SNU-484 cells. This study demonstrated that the Scutellarein on AGS and SNU-484 cells significantly inhibits cell proliferation and induces apoptotic cell death via down regulating MDM2 and activated the tumor suppresser protein p53, subsequently down regulating the IAP family proteins (cIAP1, cIAP2, and XIAP) leading to caspase-dependent apoptosis in AGS and SNU-484 cells.

Pectolinarigenin Induced Cell Cycle Arrest, Autophagy, and Apoptosis in Gastric Cancer Cell via PI3K/AKT/mTOR Signaling Pathway

“…Apoptosis is accompanied with a reduction of the G1 phase cells and an increase in the G2/M phase cells, signifying a cell cycle arrest in G2/M phase. Moreover, similar results were observed with previous studies showing that an increase in the number of G2/M phase cells is clearly related to apoptosis [ 31 , 32 ]. In the current study, we found that PEC treatment decreased the percentage of G1 phase and increased sub-G1 and G2/M phase cells.…”

Antitumor Effects of Chrysophanol in Malignant Optic Nerve Meningioma Cell Lines are Mediated via Caspase Activation, Induction of Mitochondrial Mediated Apoptosis, Mitochondrial Membrane Depolarization and Targeting the Mitogen-Activated Protein Kinase Signaling Pathway

“…The Bcl/Bax ratio is considered an important determinant of the apoptosis induction [14] and in this study, we found that chrysophanol increased Bax expression and decreased the Bcl-2 expression, thereby causing a remarkable decrease in the Bcl-2/Bax ratio. Apoptosis is also accompanied by the activation of the caspases [15] and in this study, we found that chrysophanol induced the activation of caspase-3 and 9 in a dose-dependent pattern. These observations are also supported by previous studies where chrysophanol has been shown to trigger apoptosis of the breast cancer cells [16].…”

Effects of epigenetic pathway inhibitors on corticotroph tumour AtT20 cells

“…These findings support the hypothesis that different mechanisms may be responsible for the efficacy of JQ1 in NETs, and these may involve the apoptotic pathway, as indicated by our RNA-Seq analysis that revealed four apoptosis-associated genes (Capn9, Dffb, Birc3 and Nfkb1) to be downregulated by JQ1 treatment. Birc3 encodes cIAP2, which is an E3 ubiquitin protein ligase that is a member of the inhibitors of apoptosis proteins (IAP) family, and increases cIAP2 expression that can lead to evasion of caspase-mediated apoptosis in different cancers including gastric and gallbladder cancers and glioblastoma (Wang et al 2016, Jiang et al 2017, Gowda Saralamma et al 2018. In addition, cIAP2 has been reported to activate NFκB (encoded by Nfkb1) signalling, which also has roles in apoptosis regulation (Tchoghandjian et al 2013, Jiang et al 2017.…”