Cell-cycle arrest and p53-independent induction of apoptosis in vitro by the new anticancer drugs 5-FdUrd- P -FdCydOct and dCydPam- P -FdUrd in DU-145 human prostate cancer cells

Cattaneo-Pangrazzi, Rosanna M. C.; Schott, Herbert; Wunderli‐Allenspach, Heidi; Rothen‐Rutishauser, Barbara; Guenthert, Maja; Schwendener, Reto A.

doi:10.1007/s004320050339

Cited by 16 publications

(6 citation statements)

References 17 publications

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“…Results of flow cytometric analysis showed that BPSQ induced a block in S phase. Comparable effect on cell cycle arrest was reported for other compounds as well [44][45][46]. The observed reduction in the level of p-histone H3 and PCNA after the treatment with BPSQ further supports cell cycle arrest at S phase.…”

Section: Discussionsupporting

confidence: 82%

A novel DNA intercalator, butylamino-pyrimido[4′,5′:4,5]selenolo(2,3-b)quinoline, induces cell cycle arrest and apoptosis in leukemic cells

et al. 2009

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DNA intercalators are one of the most commonly used chemotherapeutic agents. Novel intercalating compounds of pyrimido[4',5':4,5]selenolo(2,3-b)quinoline series having a butylamino or piperazino group at fourth position (BPSQ and PPSQ, respectively) are studied. Our results showed that BPSQ induced cytotoxicity whereas PPSQ was cytostatic. The cytotoxicity induced by BPSQ was concentration- and time-dependent. Cell cycle analysis and tritiated thymidine assay revealed that BPSQ affects the cell cycle progression by arresting at S phase. The absence of p-histone H3 and reduction in the levels of PCNA in the cells treated with BPSQ further confirmed the cell cycle arrest. Further, annexin V staining, DNA fragmentation, nuclear condensation and changes in the expression levels of BCL2/BAD confirmed the activation of apoptosis. Activation of caspase 8 and lack of cleavage of caspase 9, caspase 3 and PARP suggest the possibility of BPSQ triggering extrinsic pathway for induction of apoptosis, which is discussed. Hence, we have identified a novel compound which would have clinical relevance in cancer chemotherapeutics.

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Section: Discussionsupporting

confidence: 82%

A novel DNA intercalator, butylamino-pyrimido[4′,5′:4,5]selenolo(2,3-b)quinoline, induces cell cycle arrest and apoptosis in leukemic cells

et al. 2009

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“…A study demonstrated that almost 50% of human tumors carry p53 mutations, and that additional mechanisms are able to disrupt wild-type p53 function (18). Although a number of studies have shown that apoptosis may be induced in a p53-independent manner (19)(20)(21)(22)(23)(24)(25)(26), other studies have reported that p53 is actively required for apoptosis to occur (24,27,28). The action of p53 has been shown to operate predominantly through induction of apoptosis in cells via the intrinsic pathway (29,30).…”

Section: Discussionmentioning

confidence: 99%

Deoxycholic acid inhibits the growth of BGC-823 gastric carcinoma cells via a p53-mediated pathway

Yang

Song

Cheng

et al. 2014

Molecular Medicine Reports

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The aim of the present study was to investigate the effects of deoxycholic acid (DCA) on BGC‑823 human gastric carcinoma cells and to explore the possible mechanisms underlying any such effects. Cell proliferation was detected using a 3‑(4,5‑Dimethylthiazol‑2‑yl)‑2,5‑diphenyl tetrazolium bromide assay, cell morphology was observed by inverted microscopy, and cell cycle progression and the mitochondrial membrane potential were analyzed using flow cytometry. The expression of Bcl‑2, Bax, p53, Cyclin D1 and cyclin‑dependent kinase (CDK)2 proteins in BGC‑823 cells was analyzed with western blotting. The results demonstrated that DCA significantly inhibited cell growth, and that the cell cycle was arrested at the G1 phase. DCA was also shown to induce BGC‑823 cell apoptosis, which was associated with the collapse of the mitochondrial membrane potential. The mitochondria‑dependent pathway was activated via an increase in the ratio of Bax:Bcl‑2 in BGC‑823 cells. In addition, the expression of p53, cyclin D1 and CDK2 was altered following DCA treatment. These results suggest that DCA induces apoptosis in gastric carcinoma cells through activation of an intrinsic mitochondrial‑dependent pathway, in which p53 is involved.

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“…They included four p53 mutant cells (PC3, DU145, MDA-MB-231, Hs578T) (25)(26)(27)(28) and three p53-positive cells (MCF-7, BT549, HeLa) (25, 28 -30). Among the breast cancer cell lines, two were ER-negative (MDA-MB-231, Hs578T) (28) and two were ER-positive (MCF-7, BT549) (28,29).…”

Section: Cells Lines and Prostate Tissue Samples-mentioning

confidence: 99%

Cellular Response to an Antisense-mediated Shift of Bcl-x Pre-mRNA Splicing and Antineoplastic Agents

Mercatante¹,

Mohler²,

Kole³

2002

Journal of Biological Chemistry

157

121

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Overexpression of Bcl-xL, an anti-apoptotic member of the Bcl-2 family, negatively correlates with the sensitivity of various cancers to chemotherapeutic agents. We show here that high levels of expression of Bcl-xL promoted apoptosis of cells treated with an antisense oligonucleotide (5′Bcl-x AS) that shifts the splicing pattern of Bcl-x pre-mRNA from the anti-apoptotic variant, Bcl-xL, to the pro-apoptotic variant, Bcl-xS. This surprising finding illustrates the advantage of antisense-induced modulation of alternative splicingversusdown-regulation of targeted genes. It also suggests a specificity of the oligonucleotide effects since non-cancerous cells with low levels of Bcl-xL should resist the treatment. 5′Bcl-x AS sensitized cells to several antineoplastic agents and radiation and was effective in promoting apoptosis of MCF-7/ADR cells, a breast cancer cell line resistant to doxorubicin via overexpression of themdr1gene. Efficacy of 5′Bcl-x AS combined with chemotherapeutic agents in the PC3 prostate cancer cell line may be translated to clinical prostate cancer since recurrent prostate cancer tissue samples expressed higher levels of Bcl-xL than benign prostate tissue. Treatment with 5′Bcl-x AS may enhance the efficacy of standard anti-cancer regimens and should be explored, especially in recurrent prostate cancer.

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Cell-cycle arrest and p53-independent induction of apoptosis in vitro by the new anticancer drugs 5-FdUrd- P -FdCydOct and dCydPam- P -FdUrd in DU-145 human prostate cancer cells

Abstract: The new dimers dCydPam-P-FdUrd and 5-FdUrd-P-FdCydOct are effective prodrugs of 5-FdUrd and have potential value for the treatment of p53-mutated and hormone-independent human prostate carcinomas.

Cited by 16 publications

References 17 publications

A novel DNA intercalator, butylamino-pyrimido[4′,5′:4,5]selenolo(2,3-b)quinoline, induces cell cycle arrest and apoptosis in leukemic cells

A novel DNA intercalator, butylamino-pyrimido[4′,5′:4,5]selenolo(2,3-b)quinoline, induces cell cycle arrest and apoptosis in leukemic cells

Deoxycholic acid inhibits the growth of BGC-823 gastric carcinoma cells via a p53-mediated pathway

Cellular Response to an Antisense-mediated Shift of Bcl-x Pre-mRNA Splicing and Antineoplastic Agents

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