Kaisheng Liu

University of Jinan (Jinan, China), Chi-nan-shih, Shandong Sheng, China

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Publications (4)10.02 Total impact

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    ABSTRACT: 17-Allylamino-17-demethoxygeldanamycin (17-AAG), a typical Hsp90 inhibitor derived from geldanamycin (GA), has entered Phase III clinical trials for cancer therapy. However, it has several signfiicantlimitations such as poor solubility, limited bioavailability and unacceptable hepatotoxicity. In this study, the anticancer activity and mechanism of SNX-25a, a novel Hsp90 inhibitor, was investigated comparing with that of 17-AAG. We showed that SNX-25a triggered growth inhibition more sensitively than 17-AAG against many human cancer cells, including K562, SW-620, A375, Hep-2, MCF-7, HepG2, HeLa, and A549 cell lines, especially at low concentrations (< 1 μM). It showed low cytotoxicity in L-02, HDF and MRC5 normal human cells. Compared with 17-AAG, SNX-25a was more potent in arresting the cell cycle at G2 phase, and displayed more potent effects on human cancer cell apoptosis and Hsp90 client proteins. It also exhibited a stronger binding affinity to Hsp90 than 17-AAG using molecular docking. Considering the superiority effects on Hsp90 affinity, cell growth, cell cycle, apoptosis, and Hsp90 client proteins, SNX-25a is supposed as a potential anticancer agent that needs to be explored in detail.
    Biochemical and Biophysical Research Communications 05/2014; 450(1). DOI:10.1016/j.bbrc.2014.05.076 · 2.30 Impact Factor
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    ABSTRACT: Heat shock protein 90 (Hsp90) has been predicted to be involved in hepatocellular carcinoma (HCC) therapy; however, the mechanisms of action remain elusive. SNX-2112 is an Hsp90 inhibitor showing broad antitumor activity. Here we aim to determine the role of the endoplasmic reticulum (ER) stress in SNX-2112-induced apoptosis in HCC cells. In general, three HCC cells (i.e., HepG2, Huh7, and SK-Hep1) were used in our experiments. The cell viability was determined by the CCK-8 assay. The apoptosis was analyzed using flow cytometry, laser scanning confocal microscopy (LSM) and Western blotting. The efficacy and mechanisms of action of SNX-2112 were also evaluated in a mouse xenograft model. We found that SNX-2112 showed stronger inhibition on cell growth than 17-AAG, a classical Hsp90 inhibitor. SNX-2112 treatment led to the caspase-dependent apoptosis. Interestingly, SNX-2112 decreased the expression levels of the ER chaperone proteins calnexin and immunoglobulin binding protein (BiP). It also inhibited all three ER stress sensors, namely, inositol-requiring gene 1 (IRE1), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF-6) in vitro and/or in vivo. However, the ER stress inducer tunicamycin strongly enhanced SNX-2112-induced apoptosis, whereas the IRE1 knockdown did not. Taken together, we for the first time indicated the possible apoptotic pathways of SNX-2112 in HCC cells, raising the possibility that the induction of ER stress might be favorable for SNX-2112-induced apoptosis.
    Biochemical and Biophysical Research Communications 03/2014; 446(1). DOI:10.1016/j.bbrc.2014.02.081 · 2.30 Impact Factor
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    ABSTRACT: Heat shock protein 90 (Hsp90) serves as an ATP-dependent molecular chaperone for numerous cell signaling proteins, including many oncogenes and clinically validated cancer targets that are involved in cell proliferation and survival. Recent studies have shown that the Hsp90 inhibitor, SNX-2112, effectively inhibits tumor cell growth and angiogenesis in hematological and solid tumors. However, little is known about the effects of SNX-2112 on leukemias that are resistant to chemotherapy, which is emerging as a major clinical problem. In this study, the effects of SNX-2112 on the multidrug-resistant human chronic myeloid leukemia (CML) K562/ADR cell line were investigated. We observed that SNX-2112 exhibited dose- and time-dependent inhibitory activities against K562/ADR cells. These effects included the induction of apoptosis and secondary necrosis in addition to cell cycle arrest at the G1 and G2 phases. Furthermore, SNX-2112-induced apoptosis was predominantly mediated by the mitochondrial pathway, initiated by the release of cytochrome c and the participation of Bcl-2 family proteins. SNX-2112 also induced the activation of the caspase-3, -8 and -9 cascade and the subsequent cleavage of PARP in K562/ADR cells. Moreover, the inactivation of the Akt and NF-κB signaling pathways may be involved in SNX-2112-induced apoptosis. The expression levels of P-glycoprotein (P-gp) and several chaperons related to drug resistance and apoptosis were also shown to be inhibited, including the Grp78 and Hsp90 isoforms, Grp94 and Trap1. Taken together, these results provide a possible molecular mechanism for the anti-cancer effect of SNX-2112 on K562/ADR cells and provide new insights into the future application of SNX-2112 as a therapeutic agent for anti-multidrug-resistant leukemias.
    Chemico-biological interactions 06/2013; 205(1). DOI:10.1016/j.cbi.2013.06.007 · 2.58 Impact Factor
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    ABSTRACT: A new fungal strain, displaying strong toxic activity against brine shrimp larvae, was isolated from a deep sea sediment sample collected at a depth of 1300 m. The strain, designated as F00120, was identified as a member of the genus Penicillium on the basis of morphology and ITS sequence analysis. One new sesquiterpene quinone, named penicilliumin A (1), along with two known compounds ergosterol (2) and ergosterol peroxide (3), were isolated and purified from the cultures of F00120 by silica gel column, Sephadex LH-20 column, and preparative thin layer chromatography. Their structures were elucidated by detailed nuclear magnetic resonance (NMR) and mass spectroscopic (MS) analysis as well as comparison with literature data. The new compound penicilliumin A inhibited in vitro proliferation of mouse melanoma (B16), human melanoma (A375), and human cervical carcinoma (Hela) cell lines moderately.
    Marine Drugs 12/2012; 10(1):106-15. DOI:10.3390/md10010106 · 2.85 Impact Factor

Publication Stats

28 Citations
10.02 Total Impact Points


  • 2014
    • University of Jinan (Jinan, China)
      Chi-nan-shih, Shandong Sheng, China
  • 2012-2013
    • Jinan University (Guangzhou, China)
      Shengcheng, Guangdong, China