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Alsterpaullone (Alp) is a small-molecule inhibitor that targets cyclin-dependent kinases to inhibit tumor cell activity. However, to the best of our knowledge, the effect of Alp on hepatoblastoma has not been investigated. Therefore, the function of Alp in apoptotic induction of hepatoblastoma cells and a potential mechanism of action were investigated. Results indicated that low doses of Alp (1 µM) significantly induced apoptosis in the HepG2 hepatoblastoma cell line. In vivo experiments of tumor suppression further indicated that Alp (3 mg/kg) exerted an inhibitory effect on HepG2 ×enograft tumor growth. Following Alp treatment, the expression level of B-cell lymphoma 2 (Bcl-2)-associated X protein, and cleaved caspase-3 and −9 in HepG2 cells was significantly increased; however, the expression of Bcl-2 was significantly decreased. In addition, phosphorylation of p38 mitogen-activated protein kinase (MAPK) significantly decreased Alp-induced caspase-3 and −9 activation. These results suggested that Alp induces apoptosis and inhibited proliferation via the p38MAPK signaling pathway. Therefore, Alp may be a therapeutic agent for treating hepatoblastoma. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis is a chronic, progressive, lethal lung disease characterized by alveolar cell necrosis and dysplasia of interstitial fibrotic tissue, resulting in loss of lung function and eventual respiratory failure. Previously, glucocorticoid drugs were used to treat this lung disorder. However, positive responses were recorded in less than half of treated patients and the cytotoxicity caused by high dosage treatment is still a concern. The present study investigated whether ulinastatin, a typical urinary trypsin inhibitor that mitigates numerous inflammatory responses, could be a treatment option for lung fibrosis. The results demonstrated that ulinastatin had the ability to ameliorate interstitial fibrosis and alveolar exudates and to protect against lung diseases induced by smoke, irradiation or silica particles. The mechanism of ulinastatin resulted in the downregulation of inflammatory cascades: Transforming growth factor-β1, tumor necrosis factor-a and nuclear factor-κB, as demonstrated by western blotting and ELISA. Ulinastatin treatment with a high dose (100,000 U/kg body weight/day) resulted in an attenuated inflammatory response, and inhibited fibrosis formation in lungs, suggesting that ulinastatin may become a part of a clinical therapeutic strategy. [ABSTRACT FROM AUTHOR]