Synergistic effects of retinoic acid and 8-Cl-cAMP on apoptosis require caspase-3 activation in human ovarian cancer cells

Srivastava, Rakesh K.; Srivastava, Aparna R.; Cho‐Chung, Yoon S.; Longo, Dan L.

doi:10.1038/sj.onc.1202464

Cited by 37 publications

(24 citation statements)

References 33 publications

(40 reference statements)

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“…Earlier it was shown that DNA-PKcs do not change significantly after Cbl treatment until 3 h of treatment, but reduction of kinase activity was observed in Cbl cos -treated drug-sensitive cells. 15 It is possible that after COS treatment in Cbl-treated drug-resistant cells, DNA-PKcs catalytic subunit is degraded by caspases, 29 as previously shown in other tumor cells.…”

Section: Discussionmentioning

confidence: 88%

“…This reduced mRNA expression and protein level in Cbl cos cells may be essential for inhibition of tumorigenicity, such as cell proliferation and spreading, before apoptosis and may induce apoptosis as observed in other tumor cells. 28 DNA-PKc, a critical DNA repair protein, travels to the cytoplasm and interacts with caspases 29 to induce apoptosis. Co-immunoprecipitation studies (Figures 3e and f) with the ARHGEF6 antibody suggest that DNA-PKc physically interacts with ARGEF6 in Cbl cos -treated cells.…”

Section: Resultsmentioning

confidence: 99%

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Gene network analysis of oxidative stress-mediated drug sensitivity in resistant ovarian carcinoma cells

Maiti

2009

Pharmacogenomics J

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Drug resistance in cancer cells involves complex molecular mechanisms and ovarian carcinoma cells become resistant to chlorambucil (Cbl) after continuous treatment. This drug-and ionizing radiation-resistant cells have lower level of endogenous ROS (reactive oxygen species) compared with sensitive cells. Elevation of the cellular ROS level by exogenous ROS generation increases the sensitivity of Cbl to resistant cells. In contrast, antioxidants prevent the sensitization of resistant cells to Cbl by H 2 O 2 , COS (chronic oxidative stress) or NOO À . The molecular mechanism of drug sensitivity with COS has been investigated by microarray gene expressions followed by gene network analysis and it reveals that a cdc42/rac1 guanine exchange factor, ARHGEF6, with p53 and DNA-Pkc (PRKDC) is central to induce apoptosis in Cbl cos (Cbl with COS) cells. mRNA and protein levels of major gene network pathway differ significantly in Cbl cos cells than in Cbltreated cells. Moreover, DNA-PKc physically interacts with ARHGEF6 and p53 mostly in the nucleus of Cbl-treated cells, whereas in Cbl cos -treated cells, its interactions are mostly in the cytoplasm. These results suggest that low doses of Cbl and very low doses of COS together kill Cbl-resistant ovarian carcinoma cells and ARHGEF6 signaling may have an instrumental role in induction of apoptosis in Cbl cos cells.

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Section: Discussionmentioning

confidence: 88%

Section: Resultsmentioning

confidence: 99%

Gene network analysis of oxidative stress-mediated drug sensitivity in resistant ovarian carcinoma cells

Maiti

2009

Pharmacogenomics J

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“…The consequences of anchoring of PDE4D5 via RACK1 on cellular functions, in general, and on cell growth, in particular, have not yet been determined. However, other studies indicate that increases in cAMP (Srivastava et al, 1999) and leukemic cells (Myklebust et al, 1999;Thompson et al, 1999).…”

Section: Phosphodiesterase 4d5mentioning

confidence: 96%

Adaptor proteins in protein kinase C-mediated signal transduction

2001

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Spatial and temporal organization of signal transduction is essential in determining the speed and precision by which signaling events occur. Adaptor proteins are key to organizing signaling enzymes near their select substrates and away from others in order to optimize precision and speed of response. Here, we describe the role of adaptor proteins in determining the speci®c function of individual protein kinase C (PKC) isozymes. These isozymeselective proteins were called collectively RACKs (receptors for activated C-kinase). The role of RACKs in PKC-mediated signaling was determined using isozyme-speci®c inhibitors and activators of the binding of each isozyme to its respective RACK. In addition to anchoring activated PKC isozymes, RACKs anchor other signaling enzymes. RACK1, the anchoring protein for activated bIIPKC, binds for example, Src tyrosine kinase, integrin, and phosphodiesterase. RACK2, the ePKC-speci®c RACK, is a coated-vesicle protein and thus is involved in vesicular release and cell ± cell communication. Therefore, RACKs are not only adaptors for PKC, but also serve as adaptor proteins for several other signaling enzymes. Because at least some of the proteins that bind to RACKs, including PKC itself, regulate cell growth, modulating their interactions with RACKs may help elucidate signaling pathways leading to carcinogenesis and could result in the identi®cation of novel therapeutic targets. Oncogene (2001) 20, 6339 ± 6347.

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“…Treatment of Jurkat cells with TRAIL resulted in BID cleavage in a dose-dependent manner (Figure 4c), suggesting that BID is a substrate for caspase-8. Since DNA repair enzyme poly(ADPribose) polymerase (PARP) is cleaved by caspases during apoptosis (Lazebnik et al, 1994;Martin and Green, 1995;Srivastava et al, 1999d) Mitochondrial permeability transition (MPT) refers to the regulated opening of a large, nonspeci®c pore in the inner mitochondrial membrane (Green and Reed, 1998). The MPT causes the loss of the mitochondrial membrane potential (Dc m ) (Green and Reed, 1998).…”

Section: Caspase Inhibitors Inhibit Trail-induced Apoptosismentioning

confidence: 99%

Intracellular mechanisms of TRAIL: apoptosis through mitochondrial-dependent and -independent pathways

et al. 2001

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Tumor necrosis (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family of cytokines that promotes apoptosis. TRAIL induces apoptosis via death receptors (DR4 and DR5) in a wide variety of tumor cells but not in normal cells. The objectives of this study are to investigate the intracellular mechanisms by which TRAIL induces apoptosis. The death receptor Fas, upon ligand binding, trimerizes and recruits the adaptor protein FADD through the cytoplasmic death domain of Fas. FADD then binds and activates procaspase-8. It is unclear whether FADD is required for TRAIL-induced apoptosis. Here we show that the signaling complex of DR4/DR5 is assembled in response to TRAIL binding. FADD and caspase-8, but not caspase-10, are recruited to the receptor, and cells de®cient in either FADD or caspase-8 blocked TRAIL-induced apoptosis. In addition, TRAIL initiates the activation of caspases, the loss of mitochondrial transmembrane potential (Dc m ), the cleavage of BID, and the redistribution of mitochondrial cytochrome c. Treatment of Jurkat cells with cyclosporin A delayed TRAIL-induced Dc m , caspase-3 activation and apoptosis. Similarly, Overexpression of Bcl-2 or Bcl-X L delayed, but did not inhibit, TRAIL-induced Dc m and apoptosis. In contrast, XIAP, cowpox virus CrmA and baculovirus p35 inhibited TRAIL-induced apoptosis. These data suggest that death receptors (DR4 and DR5) and Fas receptors induced apoptosis through identical signaling pathway, and TRAIL-induced apoptosis via both mitochondrial-dependent and -independent pathways. Oncogene (2001) 20, 2122 ± 2133.

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Synergistic effects of retinoic acid and 8-Cl-cAMP on apoptosis require caspase-3 activation in human ovarian cancer cells

Cited by 37 publications

References 33 publications

Gene network analysis of oxidative stress-mediated drug sensitivity in resistant ovarian carcinoma cells

Gene network analysis of oxidative stress-mediated drug sensitivity in resistant ovarian carcinoma cells

Adaptor proteins in protein kinase C-mediated signal transduction

Intracellular mechanisms of TRAIL: apoptosis through mitochondrial-dependent and -independent pathways

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