Central role of mitochondria and p53 in PUVA-induced apoptosis in human keratinocytes cell line NCTC-2544

Viola, Giampietro; Fortunato, Elena; Cecconet, Laura; Giudice, Laura del; Dall’Acqua, Francesco; Basso, Giuseppe

doi:10.1016/j.taap.2007.10.004

Cited by 41 publications

(47 citation statements)

References 39 publications

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“…Adherent cells were washed three times with PBS and incubated with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. MTT test was performed as previously described [23] to quantify the attached cells.…”

Section: Cell Adhesion Assaymentioning

confidence: 99%

TR-644 a novel potent tubulin binding agent induces impairment of endothelial cells function and inhibits angiogenesis

et al. 2013

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TR-644 is a novel combretastatin A-4 (CA-4) analogue endowed with potent microtubule depolymerizing activity superior to that of the lead compound and it also has high affinity to colchicines binding site of tubulin. We tested TR-644 anti-angiogenic effects in human umbilical endothelial cells (HUVEC). It showed no significant effects on the growth of HUVEC cells at concentrations below 1,000 nM, but at much lower concentrations (10-100 nM) it induced inhibition of capillary tube formation, inhibition of endothelial cell migration and affected endothelial cell morphology as demonstrated by the disruption of the microtubule network. TR-644 also increased permeability of HUVEC cells in a time dependent manner. The molecular mechanism for the anti-vascular activity of TR-644 was investigated in detail. TR-644 caused G2/M arrest in endothelial cells and this effect correlated with downregulation of the expression of Cdc25C and Cdc2Tyr15 .Moreover TR-644 inhibited VEGF-induced phosphorylation of VE-cadherin but did not prevent the VEGF-induced phosphorylation of FAK. In chick chorioallantoic membrane in vivo assay, TR-644 (0.1-1.0 pmol/egg) efficiently counteracted the strong angiogenic response induced by FGF. Also CA-4, used as reference compound, caused an antagonistic effect, but in contrast, it induced per se, a remarkable angiogenic response probably due to an inflammatory reaction in the site of treatment. In a mice allogenic tumor model, immunohistochemical staining of tumors with anti-CD31 antibody showed that TR-644 significantly reduced the number of vessel, after 24 h from the administration of a single dose (30 mg/Kg).

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Section: Cell Adhesion Assaymentioning

confidence: 99%

TR-644 a novel potent tubulin binding agent induces impairment of endothelial cells function and inhibits angiogenesis

et al. 2013

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“…It has been shown that photoactivated psoralen (PUVA) can induce p53, ␥H2AX, and cell-cycle arrest and apoptosis (Mogi et al, 2008;Viola et al, 2008). The precise mechanism by which psoralen lesions induce these responses is not known.…”

Section: Resultsmentioning

confidence: 99%

“…However, psoralen-induced ICLs have been shown to induce DNA damage responses such as phosphorylation of the histone variant H2AX (␥H2AX) throughout the cell cycle and induce an arrest at the G 1 /S border of the cell cycle (Mogi et al, 2008;Viola et al, 2008). We and others have shown that agents that block transcription induce p53 (Yamaizumi and Sugano, 1994;Ljungman and Zhang, 1996;Ljungman and Lane, 2004) and apoptosis in human cells (Ljungman and Zhang, 1996;McKay et al, 1998;Brash et al, 2001).…”

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confidence: 99%

Psoralen-Induced DNA Interstrand Cross-Links Block Transcription and Induce p53 in an Ataxia-Telangiectasia and Rad3-Related-Dependent Manner

Derheimer¹,

Hicks²,

Paulsen³

et al. 2008

Mol Pharmacol

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Psoralen plus UVA light (PUVA) is commonly used to treat psoriasis, a common skin disorder associated with rapid proliferation of cells. PUVA exerts its antiproliferative activity through formation of DNA monoadducts and interstrand crosslinks (ICLs). However, this treatment may lead to skin malignancies as a direct result of inducing carcinogenic DNA damage. Inactivation of the p53 tumor suppressor gene is an important event in the development of skin cancer. p53 is rapidly phosphorylated and stabilized in response to DNA damage, and the induction of apoptosis by p53 is an important mechanism by which p53 exerts its tumor-suppressive activity. To better understand the mechanism by which PUVA treatment induces p53, we exposed human skin fibroblasts with PUVA under conditions that differentially produce monoadducts and ICLs and found that psoralen-induced ICLs induced phosphorylation of the Ser-15 site of p53 and apoptosis much more effectively than psoralen-induced monoadducts. The induction of p53 phosphorylation by psoralen ICLs did not require factors believed to be involved in the repair of psoralen ICLs [xeroderma pigmentosum (XP)-A, XP-C, XP-F, Cockayne's syndrome-B, Fanconi anemia] but did require the ataxia-telangiectasia and Rad3-related but not the ataxia-telangiectasia mutated kinase. Psoralen-induced ICLs blocked transcription and replication more efficiently than monoadducts, and induction of p53 and apoptosis correlated with doses causing interference with transcription rather than DNA replication. Our finding that cells underwent apoptosis preferentially during S-phase suggests that the combined blockade of transcription and DNA replication by psoralen ICLs during S-phase elicits a strong apoptotic response.

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“…waf/Cip and p53 activation, with mitochondrial-induced cytochrome c release and the consequent apoptotic reaction [31] .…”

Section: Effects On Normal Cellsmentioning

confidence: 99%

Effects of psoralens as anti-tumoral agents in breast cancer cells

Panno

Giordano

2014

WJCO

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Core tip: This review examines the biological properties of coumarins by considering their beneficial effects in the prevention of some diseases and as anti-cancer agents. The attention is mainly focused on the effects of psoralens on human breast cancer as they are able to influence many aspects of cell behavior. More recently, it has been reported that these drugs in breast cancer cells are capable of antagonizing some metabolizing enzymes, to affect estrogen receptor stability and to counteract cell invasiveness as well as cancer drug resistance.Panno ML, Giordano F. Effects of psoralens as anti-tumoral agents in breast cancer cells.

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Central role of mitochondria and p53 in PUVA-induced apoptosis in human keratinocytes cell line NCTC-2544

Cited by 41 publications

References 39 publications

TR-644 a novel potent tubulin binding agent induces impairment of endothelial cells function and inhibits angiogenesis

TR-644 a novel potent tubulin binding agent induces impairment of endothelial cells function and inhibits angiogenesis

Psoralen-Induced DNA Interstrand Cross-Links Block Transcription and Induce p53 in an Ataxia-Telangiectasia and Rad3-Related-Dependent Manner

Effects of psoralens as anti-tumoral agents in breast cancer cells

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