Enhancement of chemosensitivity toward anticancer drugs by high expression of caspase-1 in NIH 3T3 cells

Hiwasa, Takaki; Tokita, Hisashi; Sato, Shigeru; Nakagaware, Akira

doi:10.1097/00001813-199801000-00010

Cited by 8 publications

(5 citation statements)

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“…Overexpression of procaspase-3 protein was not accompanied by spontaneous caspase-3 activation and we could not detect mature p17 subunits in the procaspase-3-transfected clones ( Figure 5a). As a consequence, the stable overexpression of procaspase-3 alone induced neither apoptosis-like cell death nor morphological changes (data not shown) thereby con®rming similar observations in NIH3T3 cells using procaspase-1 (Hiwasa et al, 1998). Nevertheless, we tested whether the higher levels of procaspase-3 in positive clones could be in vitro activated by addition of 1 mM dATP and 10 mM cytochrome c thus resulting in higher speci®c enzyme activities.…”

Section: Characterization Of Mt1/adr Clonessupporting

confidence: 62%

Overexpression of caspase-3 restores sensitivity for drug-induced apoptosis in breast cancer cell lines with acquired drug resistance

et al. 2001

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Section: Characterization Of Mt1/adr Clonessupporting

confidence: 62%

Overexpression of caspase-3 restores sensitivity for drug-induced apoptosis in breast cancer cell lines with acquired drug resistance

et al. 2001

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“…The activity of mitochondrial succinic dehydrogenase was measured by incubation for 4 h in the presence of MTT (0.5 mg/ml) followed by measurement of absorbance at 570 nm with a reference wavelength of 655 nm according to the method of Mosmann 67 as described previously. 68 Absorbance reflects the viable cell number, and was expressed as a percentage of that of unirradiated cells cultured in the absence of ALLN.…”

Section: Methods For Assessing Viabilitymentioning

confidence: 99%

Increase in ultraviolet sensitivity by overexpression of calpastatin in ultraviolet-resistant UVr-1 cells derived from ultraviolet-sensitive human RSa cells

et al. 2000

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Human RSa cells are highly sensitive to apoptotic-like cell death by ultraviolet irradiation (UV) while UV r -1 cells are their variant with an increased resistance to UV. Three days after UV at 10 J/m 2 , the viability of RSa cells was approximately 17% while that of UV r -1 cells was 65%. This different survival might reflect apoptotic cell death since apoptosis-specific DNA ladder was more clearly observed in RSa cells than in UV r -1 cells after UV. Addition of ALLN/calpain inhibitor I to the culture medium after UV resulted in similar survival (14 ± 18%) between RSa and UV r -1 cells. Immunoblot analysis showed down-regulation of protein kinase Cy, Src, Bax and m-calpain after UV was more prominent in UV r -1 than in RSa cells. Activated m-calpain appeared within 1 h post-UV only in UV r -1 cells. The expression of calpastatin, a specific endogenous inhibitor of calpain, was higher in RSa than in UV r -1 cells. To further examine the role of calpain in UV-induced cell death, cDNA of human calpastatin was transfected into UV r -1 cells. The results showed that overexpression of calpastatin suppressed down-regulation of Src, m-calpain and Bax. Concomitantly, colony survival after UV was reduced in calpastatin-transfected cells as compared to vector control cells. Our results suggest that activation of calpain might account for, at least in part, the lower susceptibility to UVinduced cell death in UV r -1 cells. Cell Death and Differentiation (2000) 7, 531 ± 537.

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“…Although caspase-1 has been shown to be involved mainly in inflammation (reviewed in [18]), previous studies suggested an additional role for caspase-1 in cell death after drug exposure [5,19]. Because D4-GDI contains caspase-1 and caspase-3 cleavage sites [10], we addressed the role of caspase-1 and the central effector caspase-3 in our experimental system.…”

Section: Introductionmentioning

confidence: 99%

GDP dissociation inhibitor D4-GDI (Rho-GDI 2), but not the homologous Rho-GDI 1, is cleaved by caspase-3 during drug-induced apoptosis

et al. 2000

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Different cytotoxic drugs induce cell death by activating the apoptotic programme; a family of cysteinyl aspartate proteases named caspases has been shown to be involved in the initiation as well as the execution of this kind of cell death. In the present study, cleavage of D4-GDI (Rho-GDI 2), an abundant haemopoietic-cell GDP dissociation inhibitor for the Ras-related Rho family GTPases, was demonstrated after treatment of BJAB Burkitt-like lymphoma cells with taxol or epirubicin. The cleavage of D4-GDI occurred simultaneously with the activation of caspase-3 but preceded DNA fragmentation and the morphological changes associated with apoptotic cell death. By using high-resolution two-dimensional gel electrophoresis it was shown that this cleavage is specific: whereas the level of the homologous protein Rho-GDI 1 was not significantly altered during drug-induced apoptosis and in cytochrome c/dATP-activated cellular extracts, D4-GDI disappeared owing to proteolytic cleavage. Inhibitor experiments with Z-DEVD-fmk (in which Z stands for benzyloxycarbonyl and fmk for fluoromethyl ketone) and microsequencing of the D4-GDI fragment revealed that this occurs at the caspase-3 cleavage site. Our results strongly suggest the differential regulation of the homologous GDP dissociation inhibitors Rho-GDI 1 and D4-GDI during drug-induced apoptosis by proteolysis mediated by caspase-3 but not by caspase-1. Owing to their crucial role as modulators of Rho GTPases, this might in turn have a significant impact on the mechanisms that induce the cytoskeletal and morphological changes in apoptotic cells.

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Enhancement of chemosensitivity toward anticancer drugs by high expression of caspase-1 in NIH 3T3 cells

Cited by 8 publications

References 0 publications

Overexpression of caspase-3 restores sensitivity for drug-induced apoptosis in breast cancer cell lines with acquired drug resistance

Overexpression of caspase-3 restores sensitivity for drug-induced apoptosis in breast cancer cell lines with acquired drug resistance

Increase in ultraviolet sensitivity by overexpression of calpastatin in ultraviolet-resistant UVr-1 cells derived from ultraviolet-sensitive human RSa cells

GDP dissociation inhibitor D4-GDI (Rho-GDI 2), but not the homologous Rho-GDI 1, is cleaved by caspase-3 during drug-induced apoptosis

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