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.
Highlights
Apoptosis has been widely appreciated and intensively studied in the past two decades as a major mechanism of regulated cell death
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 leading to caspase-dependent apoptosis in AGS and SNU-484 cells
Several natural flavonoids compounds derived from plants were recently reported to cause cancer cell death by induction of apoptosis in various human cancer cells [22, 28, 29]
Summary
Apoptosis has been widely appreciated and intensively studied in the past two decades as a major mechanism of regulated cell death. The mechanisms by which obliqueness of apoptosis occurs in cancer cells mainly of three types: 1) Impaired death receptor signaling, 2) Disrupted balance of proapoptotic and anti-apoptotic proteins and 3) Reduced caspase activation [4]. The novel agents include those targeting the intrinsic Bcl-2 family pathway such as antisense bcl-2 oligonucleotides and the extrinsic pathway such as TNFR1 (Tumor necrosis factor receptor 1).There are several potent endogenous sets of genes and proteins that inhibit apoptosis. Targeting some of these dysregulated factors in cancer cells death as apoptosis-like the p53, IAPs, Bcl-2 family of proteins, and caspases activation will be decisive in cancer treatment [15]
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