Lonidamine induces apoptosis in drug-resistant cells independently of the p53 gene.

Bufalo, Donatella Del; Biroccio, Annamaria; Soddu, Silvia; Laudonio, Nina; D’Angelo, Carmen; Sacchi, Ada; Zupi, Gabriella

doi:10.1172/jci118900

Cited by 56 publications

(52 citation statements)

References 43 publications

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“…42 Briefly, cell lysates were incubated with anti-p53 monoclonal antibody (mAb) PAb 1620, (Ab-5; Oncogene Science, Uniondale, NY, USA) or PAb 240 (Ab-3; Oncogene Science). Immunocomplexes were precipitated with Immunopure Plus protein A, when using PAb 1620 (Pierce Europe, Oud Beijerland, The Netherlands), or Immunopure Plus protein G, when using PAb 240 (Pierce Europe), washed four times with lysis buffer and analyzed on SDS-PAGE.…”

Section: Analysis Of P53 Proteinmentioning

confidence: 99%

“…Indirect immunofluorescence was performed 2 days after infection with Ad-p53 or dl70.3 at MOI 10, as previously described. 42 …”

Section: Analysis Of P53 Proteinmentioning

confidence: 99%

“…42 Apoptosis was detected by flow cytometry and by morphological examination. Flow cytometric analysis of permeabilized PI-stained cells was performed as previously reported.…”

Section: Cat Assaymentioning

confidence: 99%

“…Flow cytometric analysis of permeabilized PI-stained cells was performed as previously reported. 42 Cytocentrifuge preparations were stained with Hoechst 33258 dye (Sigma, Milan, Italy) and cover-slipped. Cell morphology was evaluated by fluorescence microscopy.…”

Section: Cat Assaymentioning

confidence: 99%

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Increase of BCNU sensitivity by wt-p53 gene therapy in glioblastoma lines depends on the administration schedule

Biroccio¹,

Bufalo²,

Ricca³

et al. 1999

Gene Ther

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In this article, we investigated the effect induced by the ify the cell cycle profile in respect of Ad-p53 infected cells. reintroduction of wild-type p53 (wt-p53) protein on BCNU In contrast, BCNU→Ad-p53 sequence provoked G2-M sensitivity in the ADF glioblastoma line. Using a wt-p53 rearrest similar to that observed after treatment with BCNU combinant adenovirus (Ad-p53), we demonstrated that alone, but prevented the later recovery of the cells through exogenous wt-p53 expression was able to increase the the cell cycle, by driving the cells to apoptotic death. These sensitivity to BCNU in ADF cells. Interestingly, this effect results demonstrate that the administration sequence is was more evident when Ad-p53 infection was performed important to increase drug sensitivity. To generalize the after BCNU treatment compared with the opposite phenomenon observed on ADF line, the antiproliferative sequence. To understand the biological basis of these difeffect of the two different schedules was analyzed on other ferent behaviors, we analyzed the cell cycle of the differglioblastoma lines (A172, CRS-A2, U373MG) with different ently treated cells. We found that Ad-p53 infection induced BCNU sensitivity and p53 status. The data obtained a persistent accumulation of cells in the G0/G1 phase confirm that the wt-p53 gene transfer enhances BCNU while, as expected, BCNU induced a block in the G2-M sensitivity in glioblastoma cells depending on the phase. Ad-p53→BCNU sequence did not significantly modadministration sequence.

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Section: Analysis Of P53 Proteinmentioning

confidence: 99%

“…Indirect immunofluorescence was performed 2 days after infection with Ad-p53 or dl70.3 at MOI 10, as previously described. 42 …”

Section: Analysis Of P53 Proteinmentioning

confidence: 99%

“…42 Apoptosis was detected by flow cytometry and by morphological examination. Flow cytometric analysis of permeabilized PI-stained cells was performed as previously reported.…”

Section: Cat Assaymentioning

confidence: 99%

Section: Cat Assaymentioning

confidence: 99%

See 2 more Smart Citations

Increase of BCNU sensitivity by wt-p53 gene therapy in glioblastoma lines depends on the administration schedule

Biroccio¹,

Bufalo²,

Ricca³

et al. 1999

Gene Ther

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“…We recently reported that human ovarian cancer cell lines selected for resistance to cisplatin have reduced susceptibility to apoptosis induction after cytotoxic treatment, as a consequence of loss of wild-type p53 function (Perego et al, 1996). A correlation between apoptosis and cellular sensitivity has also been documented for LND, but LND-induced apoptosis is not mediated by the p53 gene (Del Bufalo et al, 1996).…”

mentioning

confidence: 94%

Stimulation of the apoptotic response as a basis for the therapeutic synergism of lonidamine and cisplatin in combination in human tumour xenografts

Cesare

Pratesi²,

Giusti

et al. 1998

Br J Cancer

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Summary The pharmacological interest in lonidamine is related to its ability to enhance the cytotoxic effects of several DNA-damaging antitumour agents. This study was undertaken to better understand the in vivo interaction between lonidamine and cisplatin in the treatment of human tumour xenografts, including three carcinoma models characterized by a different responsiveness to cisplatin, in spite of the presence of a wild-type p53 gene in all tumours. The drug combination was more effective in tumour growth inhibition than cisplatin alone against MX-1 breast carcinoma and A2780 ovarian carcinoma, both highly responsive to cisplatin, whereas no influence of lonidamine was observed on anti-tumour activity of cisplatin in the treatment of the relatively resistant IGROV-1 ovarian carcinoma. As cisplatin activity is related to induction of apoptosis, the modulation of drug-induced apoptosis by lonidamine was investigated. Under conditions in which lonidamine itself had negligible effects on tumour growth and apoptosis, the modulating agent stimulated the apoptotic response induced by cisplatin in the responsive but not in the resistant tumours. Tumour response was dependent not only on the drug activation of apoptosis, but mainly on the persistence over time of the event. In the breast carcinoma MX-1, hypersensitive to cisplatin and to the lonidamine+cisplatin combination, the efficacy of drug treatment was associated with phosphorylation of bcl-2 followed by down-regulation of the protein. Lonidamine itself caused a delayed phosphorylation of bcl-2. These results are consistent with the interpretation that lonidamine is effective in modulating biochemical factors involved in regulation of apoptosis.

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Functional role of α4β1 and α5β1 integrin fibronectin receptors expressed on adriamycin-resistant MCF-7 human mammary carcinoma cells

Nista¹,

Leonetti²,

Bernardini³

et al. 1997

Int. J. Cancer

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Cytofluorimetric and reverse-transcription polymerase chain reaction (RT-PCR) analysis showed that adriamycinresistant (ADR R ), but not sensitive (WT), MCF-7 human mammary carcinoma cell lines express a4b1 and a5b1 integrins. ADR R cells adhere to fibronectin (FN), and only a5b1 is involved in cell adhesion to this glycoprotein, while a4b1 mediates cell binding to the cellular counter-receptor VCAM-1. Proliferation assays showed that FN, but not VCAM-1, delivers a mitogenic signal to quiescent ADR R MCF-7 cells. The activating signal is mediated by a5b1, since cell proliferation is inhibited in the presence of RGD peptide or specific antibody. Cell cycle analysis demonstrated that cell/FN interaction induces the re-entry of ADR R MCF-7 into S phase, and prevents them from undergoing serum deprivation-induced apoptosis. Our data suggest that the presence of a5b1 on the resistant cells enables them to draw advantage from FN for both cell growth and survival. Int.

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Lonidamine induces apoptosis in drug-resistant cells independently of the p53 gene.

Cited by 56 publications

References 43 publications

Increase of BCNU sensitivity by wt-p53 gene therapy in glioblastoma lines depends on the administration schedule

Increase of BCNU sensitivity by wt-p53 gene therapy in glioblastoma lines depends on the administration schedule

Stimulation of the apoptotic response as a basis for the therapeutic synergism of lonidamine and cisplatin in combination in human tumour xenografts

Functional role of α4β1 and α5β1 integrin fibronectin receptors expressed on adriamycin-resistant MCF-7 human mammary carcinoma cells

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