Purpose: Marine triterpene glycosides that are physiologically active natural compounds isolated from sea cucumbers (holothurians) and sponges have antifungal, cytotoxic, and antitumor activities, whose specific molecular mechanisms remain to be elucidated. In this study, we examined if and through which mechanisms stichoposide C (STC) from Thelenota anax (family Stichopodidae) induces apoptosis in leukemia and colorectal cancer cells.Experimental Design: We examined STC-induced apoptosis in human leukemia and colorectal cancer cells in the context of mitochondrial injury and signaling pathway disturbances, and investigated the antitumor effect of STC in mouse CT-26 subcutaneous tumor and HL-60 leukemia xenograft models.Results: We found that STC induces apoptosis in these cells in a dose-dependent manner and leads to the activation of Fas and caspase-8, cleavage of Bid, mitochondrial damage, and activation of caspase-3. STC activates acid sphingomyelinase (SMase) and neutral SMase, which resulted in the generation of ceramide. Specific inhibition of acid SMase or neutral SMase and siRNA knockdown experiments partially blocked STC-induced apoptosis. Moreover, STC markedly reduced tumor growth of HL-60 xenograft and CT-26 subcutaneous tumors and increased ceramide generation in vivo.Conclusions: Ceramide generation by STC, through activation of acid and neutral SMase, may in part contribute to STC-induced apoptosis and antitumor activity. Thus, STC may have therapeutic relevance for human leukemia and colorectal cancer. Clin Cancer Res; 18(21); 5934-48. Ó2012 AACR.

The electret filter is a potential component to remove airborne particles due to its high collection efficiency and low pressure drop. However, its filtration performance is gradually decreased by exposure to organic solvents, which limits the application of electret filters. The effect of ethanol exposure on the filtration performance of polypropylene electret filters was investigated experimentally to clarify the charge decay phenomenon in this study. Experimental results revealed that filter performance is strongly dependent upon the challenged mass and existing state of an ethanol solvent. The filter performance was drastically degraded by exposure to ethanol droplets generated from a solution with ethanol concentrations above 30%; however, it was maintained during exposure to ethanol vapors. This tendency was also seen in the surface potentials of the exposed filter media. In addition, we found that the critical challenging amount of ethanol droplets was in the vicinity of 0.045 g/cm 2 to neutralize a tested electret filter in this study.

Abstract. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a coactivator interacting with multiple transcription factors, regulates several metabolic processes. Although recent studies have focused on the role of PGC-1α in cancer, the underlying molecular mechanism has not been clarified. Therefore, we evaluated the role of PGC-1α in cell proliferation and tumorigenesis using human embryonic kidney (HEK)293 cells and colorectal cancer cells. We established stable HEK293 cell lines expressing PGC-1α and examined cell proliferation, anchorage-independent growth, and oncogenic potential compared to parental HEK293 cells. To identify the molecular PGC-1α targets for increased cell proliferation and tumorigenesis, the GeneFishing™ DEG (differentially expressed genes) screening system was used. Western blot analysis and immunofluorescence staining were performed for a regulated gene product to confirm the results. Forced expression of PGC-1α in HEK293 cells promoted cell proliferation and anchorage-independent growth in soft agar. In addition, HEK293 cells that highly expressed PGC-1α showed enhanced tumor formation when subcutaneously injected into the bilateral flanks of immunodeficient mice. The results of the GeneFishing DEG screening system identified one upregulated gene (Acyl-CoA binding protein; ACBP). Real-time RT-PCR, western blot analysis, and immunofluorescence staining showed that ACBP was markedly increased in HEK293 cells stably overexpressing PGC-1α (PGC-1α-HEK293 cells) compared to those expressing an empty vector. In PGC-1α, ACBP, and specificity protein 1 (Sp1) siRNA knockdown experiments in PGC-1α-HEK293 and SNU-C4 cells, we also observed inhibition of cell proliferation, reduced expression of antioxidant enzymes, and increased H 2 O 2 -induced reactive oxygen species production and apoptosis. These findings suggest that PGC-1α may promote cell proliferation and tumorigenesis through upregulation of ACBP. We provide evidence that increased Sp1 expression might contribute to enhanced ACBP expression by PGC-1α. The current results also suggest that PGC-1α, whose expression is related to enhanced cell proliferation and tumorigenesis, may be a good candidate molecular target for cancer therapy.