Piperlongumine induces ROS mediated cell death and synergizes paclitaxel in human intestinal cancer cells
BIOMEDICINE & PHARMACOTHERAPY
Authors: Rawat, Laxminarayan; Hegde, Harsha; Hoti, Sugeerappa Laxmanappa; Nayak, Vijayashree
Abstract
Piperlongumine (PL), a herbal drug extracted from long pepper (Piper longum L), is known for its anti-inflammatory and anti-cancer properties. Although, its anti-cancer potential has been evaluated in cancer models like breast, pancreatic, gastric, hepatocellular and lung carcinoma, there is no report on its bio-activity evaluation in intestinal cancers. Here, we report the anti-neoplastic potential of PL against human intestinal carcinoma in-vitro and its possible mechanisms of action. Cytotoxicity studies demonstrate that PL inhibits cell proliferation of INT-407 and HCT-116 cells in a concentration and time-dependent manner. Also, PL elevated the levels of intracellular reactive oxygen species, which may lead to lethal oxidative stress, mitochondrial dysfunction, and nuclear fragmentation. Remarkably, P53, P21, BAX, and SMAD4 were significantly upregulated after PL treatment whereas; BCL2 and SURVIVIN were down-regulated. Moreover, the combination study also shows the synergistic effect of PL with the current chemotherapeutic drug paclitaxel. These findings suggest that PL possesses anti-neoplastic properties in intestinal cancer cells.
Interleukin Enhancer Binding Factor 2 Regulates Cell Viability and Apoptosis of Human Brain Vascular Smooth Muscle Cells
JOURNAL OF MOLECULAR NEUROSCIENCE
Authors: Wei, Liang; Yang, Cheng; Wang, Guangxue; Li, Keqin; Zhang, Yanfei; Guan, Hongxin; Sun, Zhiyang; Zhong, Chunlong
Abstract
The proliferation and migration of vascular smooth muscle cells (VSMCs) are involved in the pathogenesis of intracranial aneurysm (IA) formation and rupture. Interleukin enhancer binding factor 2 (ILF2) is known as the nuclear factor of activated T cells and regulates cell growth. This study was aimed to explore the effects ofILF2on IA progression. Human brain VSMCs (hBVSMCs) were transfected with pCDNA3.1(+), pCDNA3.1(+)-ILF2, siRNA-negative control, and siRNA-ILF2. The transfection efficiency was then evaluated by determiningILF2expression. The cell viability and apoptosis were determined using Cell Counting Kit-8 and Annexin V-FITC cell apoptosis assay kit, respectively. Real-time quantification PCR (RT-qPCR) was applied to measure the expression levels of apoptosis-related and inflammation-related genes. Finally, western blot was used to detect the expression level of Fas cell surface death receptor 95 (CD95) and Caspase 8. Overexpression ofILF2could significantly increase cell viability and decrease cell apoptosis (P < 0.05), while knock-down ofILF2showed opposite trends for hBVSMCs on cell viability and apoptosis (P < 0.05). RT-qPCR results showed thatILF2knock-down downregulated the expression levels of BCL2 apoptosis regulator (BCL2), transcriptional regulator Myc-like (c-Myc), and caspase 1 (ICE) whereas upregulated the expression levels ofCD95,p21,p53, and interleukin-13 (IL-13). Additionally, the protein expression levels of CD95 and Caspase 8 were significantly decreased afterILF2overexpression while were significantly increased afterILF2knock-down (P < 0.05).ILF2knock-down may inhibit cell viability and promote cell apoptosis of hBVSMCs by regulating the expression levels of apoptosis-related genes and suppressing inflammatory response.