Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.30 (PARP)
 13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effect of CF(3)-STLC, a potent kinesin spindle protein (KSP) inhibitor, on K562 human CML cell line was investigated. Treatment with CF(3)-STLC induced mitotic arrest of the cell cycle with the appearance of characteristic monoastral spindles, subsequent apoptotic cell death and cleavage of PARP-1, caspase-3, and 4E-BP1. The wide ranging caspase inhibitor z-VAD fmk prevented the cleavage of caspase-3 and 4E-BP1, but failed to attenuate PARP-1 cleavage or cell death triggered by CF(3)-STLC. These results suggest that CF(3)-STLC can induce apoptotic cell death in a caspase-independent manner, and may work effectively as an anti-cancer agent for hematological malignancies.
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PMID:S-trityl-L-cysteine derivative induces caspase-independent cell death in K562 human chronic myeloid leukemia cell line. 2061 60

This study was to investigate the mechanism and role of Kif4A in doxorubicin-induced apoptosis in breast cancer. Using two human breast cancer cell lines MCF-7 (with wild-type p53) and MDA-MB-231 (with mutant p53), we quantitated the expression levels of kinesin super-family protein 4A (Kif4A) and poly (ADP-ribose) Polymerase-1 (PARP-1) by Western blot after doxorubicin treatment and examined the apoptosis by flow cytometry after treatment with doxorubicin and PARP-1 inhibitor, 3-Aminobenzamide (3-ABA). Our results showed that doxorubicin treatment could induce the apoptosis of MCF-7 and MDA-MB-231 cells, the down-regulation of Kif4A and upregulation of poly(ADP-ribose) (PAR). The activity of PARP-1 or PARP-1 activation was significantly elevated by doxorubicin treatment in dose- and time-dependent manners (P < 0.05), while doxorubicin treatment only slightly elevated the level of cleaved fragments of PARP-1 (P > 0.05). We further demonstrated that overexpression of Kif4A could reduce the level of PAR and significantly increase apoptosis. The effect of doxorubicin on apoptosis was more profound in MCF-7 cells compared with MDA-MB-231 cells (P < 0.05). Taken together, our results suggest that the novel role of Kif4A in doxorubicin-induced apoptosis in breast cancer cells is achieved by inhibiting the activity of PARP-1.
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PMID:The role of Kif4A in doxorubicin-induced apoptosis in breast cancer cells. 2537 55

Kinesins act as molecular microtubule-dependent motor proteins and have various important cellular functions related to cell division, intracellular transport, and membrane trafficking. However, the function of kinesin light chain 4 (KLC4) in cancer, especially radioresistance, has not been previously described. Thus, we investigated KLC4 function in lung cancer cells and radioresistant R-H460 cells by analyzing alterations in radiosensitivity after gene knockdown with siRNA and by evaluating cellular phenotypes and xenograft tumor growth. KLC4 was upregulated in human lung cancer cell lines. Moreover, in paired clinical specimens of lung cancer patients, KLC4 expression was significantly higher in tumor tissues than in paired adjacent normal tissues. Fluorescence-activated cell sorting (FACS) analysis showed that apoptosis rates and cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspase-3 levels in KLC4-knockdown lung cancer cells were significantly increased compared with those in control cells. Colony formation decreased as the radiation dose increased in KLC4-knockdown lung cancer cells, demonstrating an essential role for KLC4 in radioresistance. Importantly, KLC4 silencing suppressed tumor growth in an in vivo xenograft model, accompanied by increased apoptosis. Finally, KLC4-knockdown cells exhibited impaired mitochondrial respiration, increased mitochondrial reactive oxygen species production, and enhanced mitochondrial calcium uptake, resulting in mitochondrial dysfunction. Thus, KLC4 as a kinesin superfamily-targeted therapy may represent a novel, effective anticancer strategy, particularly for patients showing radioresistance.
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PMID:Kinesin light chain-4 depletion induces apoptosis of radioresistant cancer cells by mitochondrial dysfunction via calcium ion influx. 2971 33