Apoptosis and the cell cycle

Meikrantz, William; Schlegel, Robert

doi:10.1002/jcb.240580205

Cited by 354 publications

(193 citation statements)

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“…Many proteins that critically regulate cell division, in fact, can also induce programmed cell death [1][2][3][4] and, vice versa, several components of the apoptotic machinery may influence the cell cycle. For instance, apoptosis regulatory proteins of the Bcl-2 family have been shown to modulate cell-cycle progression.…”

Section: Introductionmentioning

confidence: 99%

Bcl-2 activates a programme of premature senescence in human carcinoma cells

Crescenzi

Palumbo

Brady

2003

Biochemical Journal

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The apoptosis regulator Bcl-2 has been shown to modulate cellcycle progression, favouring a quiescent state over a proliferative state, in both normal and tumour cells. We show here that constitutive expression of Bcl-2 in human carcinoma cells results in a cell-cycle arrest that within a few days can become irreversible. Arrested cells acquire a senescent-like phenotype, which consists of several characteristic morphological alterations and increased activity of senescence-associated β-galactosidase. The induction of the premature senescence programme is mediated by inhibition of Cdk2 kinase activity, and p27 KIP1 is required to maintain the senescent phenotype. We propose that the ability to activate an endogenous premature senescence programme allows Bcl-2 to suppress tumour growth. These results suggest that the downregulation of Bcl-2 expression, which has been observed during the development and progression of human carcinoma, is related to the ability of Bcl-2 to severely hamper the growth of carcinoma cells and to induce a permanent cell-cycle arrest, with the features of senescence.

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Section: Introductionmentioning

confidence: 99%

Bcl-2 activates a programme of premature senescence in human carcinoma cells

Crescenzi

Palumbo

Brady

2003

Biochemical Journal

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“…34 Again, the tumor suppressor gene p53 is required for checkpoint control during cell cycle progression, as well as induction of apoptosis. 35 The overexpression of p53 inhibits cell proliferation. Increased Bcl2 expression allows the life of precancerous cells to be extended, thus facilitating malignant transformation.…”

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confidence: 99%

Suppression of cell proliferation, induction of apoptosis and cell cycle arrest: Chemopreventive activity of vanadium in vivo and in vitro

Ray

Ghosh

Rana

et al. 2006

Intl Journal of Cancer

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In the present study, the authors evaluated the anticancer mechanism of vanadium, a dietary micronutrient and an important pharmacological agent, on a defined model of chemically induced rat mammary carcinogenesis in vivo and on human breast cancer cell line MCF7 in vitro. Female Sprague-Dawley rats were treated with 7,12-dimethylbenz(a)anthracene (0.5 mg/100 g body weight) by a single tail vein injection in an oil emulsion to induce mammary preneoplasia. Vanadium (ammonium monovanadate) at a concentration of 0.5 ppm (4.27 lmol/l) was supplemented in drinking water and given ad libitum to the experimental groups for 24 weeks. Histological finding showed substantial repair of hyperplastic lesions. There was a significant reduction in incidence, multiplicity (34%, p < 0.01), size of palpable mammary tumors and delay in mean latency period of tumor appearance. Immunohistochemical analysis in vivo indicated a decrease in cell proliferation (24.68% p < 0.05) and an increase among the TUNEL-positive apoptotic cells along with strong expressions of p53 and Bax, and downregulation of Bcl2 proteins in the mammary tissue of vanadium-treated animals. Further, MCF7 cells were cultured in minimal essential medium and were treated with 100, 175 and 250 lM of vanadium (ammonium monovanadate) for 36 hr. Exposure of MCF7 cells to vanadium led to induction of apoptosis in a dose-dependent manner. It was found further that vanadium treatment brought about a prominent cell cycle arrest and chromosomal condensation, leading to apoptosis (42.62%, p < 0.05). Results of both the in vivo and in vitro study demonstrate that vanadium has the potential to be developed into an anti-breast cancer drug in the near future. ' 2006 Wiley-Liss, Inc.

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“…Although correlative in nature, consistent with this possibility is the fact that all the cells in the apoptosissensitive proliferative compartment of intestinal epithelium described above express Cdc6, but this expression becomes undetectable precisely at the transition from the proliferative to the quiescent state, where cells become refractile to apoptosis. 24 Our model might also help to explain reports of an increased sensitivity to apoptosis of mammalian cells in G1, 25 as well as the G1-specific and proliferationdependent sensitivity of budding yeast cells to the DNAdamaging drug adozelesin. 3 Once sufficient replication forks have been established in S-phase to completely replicate the genome, the destruction of pre-RCs may occur without consequence.…”

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confidence: 88%