Regulation of Caspase‐3 and Bcl‐2 Expression in Dalton′s Lymphoma Ascites Cells by Abrin

Ramnath, V.; Rekha, P. S.; Kuttan, Girija; Kuttan, Ramadasan

doi:10.1093/ecam/nem099

Cited by 26 publications

(17 citation statements)

References 24 publications

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“…Caspase-8 is activated after receiving stimulus signals and subsequently triggers the caspase protease that activates the downstream chain of hydrolases and then further activates the effector caspase-3. Studies have demonstrated that abrin P2 induces apoptosis via the mitochondrial pathway, specifically via Cyt c release or regulation of caspase-3 and Bcl-2 expressions in different types of cancer cells [16][17][18]. In this study, Z-VAD-FMK, a broad-spectrum caspase inhibitor, was found to partially abrogate abrin P2-induced apoptosis (Fig.…”

Section: Discussionmentioning

confidence: 50%

Abrin P2 suppresses proliferation and induces apoptosis of colon cancer cells via mitochondrial membrane depolarization and caspase activation

Yu¹,

Yang²,

Zhao³

et al. 2016

ABBS

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To explore the cytotoxic mechanism of abrin P2 on human colon cancer HCT-8 cells, abrin P2 was isolated from the seed of Abrus precatorius L. It was found that abrin P2 exhibited cytotoxicity toward 12 different human cancer cell lines. Our results demonstrated that abrin P2 suppressed the proliferation of human colon cancer cells (HCT-8 cells) and induced cell cycle arrest at the S and G2/M phases. The mechanism by which abrin P2 inhibited cell proliferation was via the down-regulation of cyclin B1, proliferating cell nuclear antigen and Ki67, as well as the up-regulation of P21. In addition, abrin P2 induced a dose-and time-dependent increase in the rate of HCT-8 cell apoptosis. Treatment with both Z-VAD-FMK, a broad-spectrum caspase inhibitor, and abrin P2 demonstrated that abrin P2 induced HCT-8 cell apoptosis via the activation of caspases. Together, our results revealed that abrin P2-induced apoptosis in HCT-8 cells was associated with the activation of caspases-3/-8/-9, the reduction in the Bcl-2/Bax ratio, the loss of mitochondrial membrane potential, and the increase in cytochrome c release. We further showed that abrin P2 administration effectively suppressed the growth of colon cancer xenografts in nude mice. This is the first report that abrin P2 effectively inhibits colon cancer cell growth in vivo and in vitro by suppressing proliferation and inducing apoptosis.

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Section: Discussionmentioning

confidence: 50%

Abrin P2 suppresses proliferation and induces apoptosis of colon cancer cells via mitochondrial membrane depolarization and caspase activation

Yu¹,

Yang²,

Zhao³

et al. 2016

ABBS

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“…Interestingly, overexpression of bcl-2 in DAOY and U87 cells was associated with a decrease in production of caspase 3. Although the mechanism for this coordinate, complementary regulation of expression is not known, it has recently been reported in Dalton's lymphoma ascites cells treated with the chemotherapeutic natural product, abrin [19]. Nonetheless, in bcl-2-transfected DAOY and U87 cells, increased [(relative Bcl-2 content)(relative caspase-3 content)] is associated with increased sensitivity to NCS (Fig.…”

Section: Effect Of Transfection With a Bcl-2 Expression Construct On mentioning

confidence: 93%

Molecular predictors of human nervous system cancer responsiveness to enediyne chemotherapy

Rogers

Nylander

et al. 2008

Cancer Chemother Pharmacol

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Purpose-To identify and mathematically model molecular predictors of response to the enediyne chemotherapeutic agent, neocarzinostatin, in nervous system cancer cell lines.Methods-Human neuroblastoma, breast cancer, glioma, and medulloblastoma cell lines were maintained in culture. Content of caspase-3 and Bcl-2, respectively, was determined relative to actin content for each cell line by Western blotting and optical densitometry. For each cell line, sensitivity to neocarzinostatin was determined. Brain tumor cell lines were stably transfected with human Bcl-2 cDNA cloned into the pcDNA3 plasmid vector.Results-In human tumor cell lines of different tissue origins, sensitivity to neocarzinostatin is proportional to the product of the relative contents of Bcl-2 and caspase-3 (r 2 = 0.9; p < 0.01). Neuroblastoma and brain tumor cell lines are particularly sensitive to neocarzinostatin; the sensitivity of brain tumor lines to neocarzinostatin is enhanced by transfection with an expression construct for Bcl-2 and is proportional in transfected cells to the product of the relative contents of Bcl-2 and caspase-3 (r 2 = 0.7).Conclusion-These studies underscore the potential of molecular profiling in identifying effective chemotherapeutic paradigms for cancer in general and tumors of the nervous system in particular. KeywordsEnediyne; Caspase-3; Bcl-2; Brain Tumors; Targeted Therapy Overproduction of Bcl-2 and other antiapoptotic gene products is a common mechanism of chemotherapeutic resistance. [1][2][3][4][5][6][7] We have previously reported the paradoxical potentiation by Bcl-2 of apoptosis induction by the disulfide reduction-dependent enediyne, neocarzinostatin (NCS). [8][9][10][11] As overproduction of Bcl-2 in PC12 pheochromocytoma cells is associated with increased cellular reducing potential, [12] it was hypothesized that this condition resulted in enhanced activation of NCS and consequent potentiation of apoptosis.[8] However, Bcl-2 acts downstream of NCS activation and should block apoptosis even in the face of enhanced enediyne activation. Further mechanistic studies revealed that, in PC12 neural crest tumor cells, NCS treatment results in caspase-3-dependent cleavage of Bcl-2 to its proapoptotic counterpart, [13] and that this cleavage is critical for potentiation of apoptosis by Bcl-2. [9,13] This suggests that NCS could be an effective and relatively non-toxic chemotherapeutic agent for those tumors that overproduce Bcl-2 and express caspase-3. Potentiation of efficacy would be predicted to occur only in those cells for which both conditions obtained. If this is indeed the case, it would serve as proof-of-principle for the notion of identification of molecular markers for responsiveness of particular human cancers to particular chemotherapeutic strategies.To test this hypothesis and the generalizability of the prediction it suggests, we examined the correlations between the EC 50 of NCS for cell culture growth rate depression (i.e., the concentration of NCS at which cell culture growth rate is h...

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“…Abrin isolated from seeds of Abrus precatorius [53], extract of Phyllanthus amarus [54] and Drosera indica [55] activation of caspase activated DNase mediated nuclear fragmentation has been studied in Dalton's lymphoma [56].…”

Section: T-cells Obtained Frommentioning

confidence: 99%

Dalton’s Lymphoma as a Murine Model for Understanding the Progression and Development of T-Cell Lymphoma and Its Role in Drug Discovery

Kumar¹

2017

Int J Immunother Cancer Res

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Mouse models are irreplaceable tools for the study of carcinogenesis and the availability of rodent models have enabled rational screening of drugs. Hematological malignancies have been extensively studied in mouse models and broad range of lymphoid neoplasms has been reported in laboratory mice, occurring either spontaneously or after induction with radiation, chemicals or infection of newborn mice with leukemogenic viruses. Lymphomas are tumors that generally respond well to traditional therapies such as chemotherapy and radiotherapy. Dalton's lymphoma is a transplantable T-cell lymphoma of spontaneous origin in thymus of murine host and has emerged as an interesting model for cancer research, because of its usefulness in pre-clinical system for evaluating new or known drugs in the treatment of various cancers and in drug discovery development process.

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Regulation of Caspase‐3 and Bcl‐2 Expression in Dalton′s Lymphoma Ascites Cells by Abrin

Cited by 26 publications

References 24 publications

Abrin P2 suppresses proliferation and induces apoptosis of colon cancer cells via mitochondrial membrane depolarization and caspase activation

Abrin P2 suppresses proliferation and induces apoptosis of colon cancer cells via mitochondrial membrane depolarization and caspase activation

Molecular predictors of human nervous system cancer responsiveness to enediyne chemotherapy

Dalton’s Lymphoma as a Murine Model for Understanding the Progression and Development of T-Cell Lymphoma and Its Role in Drug Discovery

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