Background:The anti-cancer activity and mechanisms of isorhapontigenin (ISO) have never been explored. Results: ISO exhibited an anti-cancer activity accompanied by apoptotic induction and XIAP down-regulation through attenuation of SP1 expression. Conclusion: ISO is an active anti-cancer compound by inducing apoptosis via down-regulation of SP1/XIAP pathway. Significance: Current studies identify a new promising active compound for therapy of human cancers with XIAP overexpression.

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Cell migration is a dynamic process that is central to a variety of physiological functions as well as disease pathogenesis. The modulation of cell migration by p27 has been reported, but the exact mechanism(s) whereby p27 intersects with downstream effectors that control cell migration have not been elucidated. By systematically comparing p27+/+ MEFs with genetically ablated p27−/− MEFs using wound healing, transwell and time-lapse microscopic analyses, we provide direct evidence demonstrating that p27 inhibits both directional and random cell migration. Identical results were obtained with normal and cancer epithelial cells using complementary knockdown and overexpression approaches. Additional studies revealed that overexpression of manganese superoxide dismutase (MnSOD) and reduced intracellular oxidation played a key role in increased cell migration in p27-deficient cells. Furthermore, we identified signal transducer and activator of transcription 3 (STAT3) as the transcription factor responsible for p27-regulated MnSOD expression which was further mediated by ERKs/ATF1-dependent transactivation of CRE within the stat3 promoter. Collectively, our data strongly indicate that p27 plays a crucially negative role in cell migration by inhibiting MnSOD expression in a STAT-3 dependent manner.

Arsenic trioxide (AsO) is an old drug that has recently been reintroduced as a therapeutic agent for acute promyelocytic leukemia (APL). Although AsO is also applied to treat other types of cancer in vitro and in vivo, it has been reported that single agent AsO has poor efficacy against non-hematologic malignant cancers in clinical trials. Recently, a few reports have indicated that organic arsenic compounds can be a possible alternative for the treatment of AsO-resistant cancers. In this study, we aimed to investigate whether the organic arsenic compound phenylarsine oxide (PAO) has potent cytotoxic effects against human hepatocellular carcinoma (HCC) HepG2 cells. Our results showed that PAO not only had a potent inhibitory effect on the proliferation of HepG2 cells but also activated apoptosis-related proteins (e.g., caspase-3 and -9 and poly-ADP ribose polymerase) in a dose- and time-dependent manner. Furthermore, intracellular ROS were specifically accumulated in the mitochondria and endoplasmic reticulum (ER) after exposure to PAO, implying that they are the target organelles for PAO-induced cytotoxicity. Additionally, when the cells were pretreated with antioxidant N-acetylcysteine (NAC), apoptosis and ER-stress were attenuated significantly, suggesting that induction of apoptosis and cell death probably occurs through the ROS-mediated mitochondria and ER-stress dependent signaling pathways.