CDDP induces p53-dependent apoptosis in tongue cancer cells.

Kanata, Hirokazu; Yane, Katsunari; Ota, Ichiro; Miyata, Hiroshi; Matsunaga, Takahiro; Takahashi, Akio; Ohnishi, Ken; Ohnishi, Takeo; Hosoi, Hiroshi

doi:10.3892/ijo.17.3.513

Cited by 10 publications

(7 citation statements)

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“…5,38) Actually, since mutations in p53 are closely associated with a worse prognosis for solid tumors, 5) it is pertinent to ask whether cells with a mutated p53 are more resistant to combined treatment with MTH and/or TPZ or not, as has been suggested for many anticancer agents. 5) In agreement with previous reports, [39][40][41] the cell-killing effect on both total and Q cell populations by a high dose of TPZ or TXL itself did not depend on p53 status (Figs. 2, (a) and (b), and 5 (a)), and SAS/neo showed greater sensitivity to γ-rays or CDDP than SAS/mp53 (Figs.…”

Section: Discussionsupporting

confidence: 92%

Usefulness of combined treatment with mild temperature hyperthermia and/or tirapazamine in the treatment of solid tumors: its independence of p53 status

Masunaga¹,

Ono²,

Takahashi³

et al. 2003

Cancer Science

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t has been shown that the p53 tumor suppressor gene serves a critical role in maintaining genomic stability during a cell cycle checkpoint in G1 and the G2/M transition, 1) and as an effector of DNA repair 2) and apoptosis.3) Wild-type p53 is needed to activate apoptosis in sensitive cells in response to DNA damage.4) These actions of p53 are potentially critical in determining the effectiveness of ionizing radiation and/or chemotherapeutic agents. Actually, mutations in the p53 tumor suppressor gene have been shown to have an impact on the clinical course of several human cancers: patients with cancers harboring p53 mutations often have a worse prognosis than those with tumors harboring wild-type p53.5) Thus, the genetic and functional status of the p53 gene is thought to be an important factor in guiding therapeutic strategies for cancer patients.Meanwhile, mild temperature hyperthermia (MTH) was reported to increase the tumor response to radiation by improving tumor oxygenation through an increase in tumor blood flow, 6) and tirapazamine (TPZ, SR-4233, WIN 59075, 3-amino-1,2,4-benzotriazine-1,4-dioxide), a well-known bioreductive agent, has highly selective cytotoxicity toward hypoxic cells in in vivo tumor systems.7) In addition, MTH was also shown to enhance the tumor response, especially of the intratumor quiescent (Q) cell population, to chemotherapy. 8) Based on these reports, we have already demonstrated that combined treatment with MTH and/or TPZ is a promising modality in radiotherapy or chemotherapy from the viewpoint of the killing effect on intratumor Q tumor cells in comparison with the total (proliferating (P)+Q) tumor cell population, using several tumor systems with wildtype p53 status. 9)Accordingly, to investigate the usefulness of MTH and/or TPZ in the treatment of solid tumors consisting of cells with a mutated p53 status, we analyzed the killing effects of several DNA-damaging cytocidal treatments combined with or without MTH and/or TPZ on intratumor Q and total cells, employing two different tumor cell lines identical in genetic background except for p53 status 10) and our method for detecting the intratumor Q cell response in terms of the micronucleus (MN) frequency and apoptosis frequency. 9) As DNA-damaging cytocidal treatments, γ-ray irradiation, TPZ administration, cisplatin (CDDP) injection and paclitaxel (TXL) treatment were employed. Materials and MethodsCells, tumors and mice. The human head and neck squamous cell carcinoma cell line SAS (provided by JCRB, Tokyo) was cultured at 37°C in Dulbecco's modified Eagle's medium (DMEM) containing 20 mM 2-[4-(2-hydroxyethyl)-1-piperazinyl]ethanesulfonic acid (HEPES) and 12.5% fetal bovine serum in a conventional humified 5% CO 2 incubator. SAS cells show the phenotype of wild-type p53 in radiation-and heat-induced signal transduction.11) Plasmids pC53-248, which contains an mp53 gene (codon 248, from Arg to Trp) producing a dominant negative mp53 protein, and pCMV-Neo-Bam, which contains a neo-resistance marker, were provided by B. Vogels...

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Section: Discussionsupporting

confidence: 92%

Usefulness of combined treatment with mild temperature hyperthermia and/or tirapazamine in the treatment of solid tumors: its independence of p53 status

Masunaga¹,

Ono²,

Takahashi³

et al. 2003

Cancer Science

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“…17 Some anticancer drugs have been confirmed to activate p53 pathway and result in cell cycle arrest, apoptosis, or cellular senescence. [19][20][21][22][23] The present study's data demonstrate that the apoptosis induced by AECA may be independent of p53, as p53 is mutant in *50% of human cancers, and in most of the remaining cancers, the functions of p53 pathway are impaired. 24 Induction of apoptosis by AECA independent of p53 is important for cancer therapy.…”

Section: Discussionmentioning

confidence: 97%

Aqueous Extract of Curcuma aromatica Induces Apoptosis and G2/M Arrest in Human Colon Carcinoma LS-174-T Cells Independent of p53

Shen

et al. 2011

Cancer Biotherapy and Radiopharmaceuticals

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Curcuma aromatica is a common Chinese herb for treating diseases with blood stasis and has been regarded as an anticancer herb in modern clinical practice. However, the anticancer effects and related molecular mechanisms of Curcuma aromatica remain unclear. In the present study, human colon carcinoma LS-174-T cell line with wild-type p53 was used as a model cell to evaluate the anticancer effects of aqueous extract of Curcuma aromatica (AECA). AECA inhibits LS-174-T cell proliferation in a dose- and time-dependent manner and colony formation in a dose-dependent manner. AECA treatment induces apoptosis accompanied by caspase-8, -9, and -3 activation in LS-174-T cells. Moreover, blocking the activities of these caspases with a specific inhibitor significantly protected LS-174-T cells from AECA-induced apoptosis. AECA treatment also induces G2/M phase arrest in LS-174-T cells. Expression of p53 was unchanged after AECA treatment; specific silence of p53 did not influence AECA-induced apoptosis and G2/M phase arrest. Further, the expression of cyclin B1 and CDK1 was reduced by AECA. This study suggests that AECA might be effective as an antiproliferative herb for colon carcinoma, the antitumor activity of AECA may involve both extrinsic and intrinsic apoptosis, and AECA induces G2/M phase arrest via downregulation of cyclin B1 and CDK1 and without the participation of p53.

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“…Among them, p53 activation is one of the major factors responsible for the apoptotic cell death induced by cisplatin (1,5). It has been observed that cisplatin can cause apoptosis in wildtype p53 cancer cells but not in p53-deficient or mutant cancer cells, suggesting that p53 is the key regulator for cisplatin-mediated apoptosis in cancer cells (6,7).…”

Section: Introductionmentioning

confidence: 99%

Luteolin sensitizes the anticancer effect of cisplatin via c-Jun NH2-terminal kinase–mediated p53 phosphorylation and stabilization

Huang¹,

Zhu²,

Ong³

et al. 2007

Molecular Cancer Therapeutics

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Luteolin is an important flavonoid with a potential anticancer effect. In this study, we examined the molecular mechanisms involved in the sensitization effect of luteolin on cancer cell killing induced by cisplatin, an important cancer chemotherapeutic agent. First, we provided evidence that the sensitization effect of luteolin on cisplatin-induced apoptosis is p53 dependent, as such effect is only found in p53 wild-type cancer cells but not in p53 mutant cancer cells. Moreover, knockdown of p53 by small interfering RNA made p53 wild-type cancer cells resistant to luteolin and cisplatin. Second, we observed a significant increase of p53 protein level in luteolin-treated cancer cells without increase of p53 mRNA level, indicating the possible effect of luteolin on p53 posttranscriptional regulation. Third, we identified the critical role of c-Jun NH 2 -terminal kinase (JNK) in regulation of p53 protein stability: luteolin activates JNK, and JNK then stabilizes p53 via phosphorylation, leading to reduced ubiquitination and proteasomal degradation. Finally, by using an in vivo nude mice xenograft model, we confirmed that luteolin enhanced the cancer therapeutic activity of cisplatin via p53 stabilization and accumulation. In summary, data from this study reveal a novel molecular mechanism involved in the anticancer effect of luteolin and support its potential clinical application as a chemosensitizer in cancer therapy. [Mol Cancer Ther 2007;6(4):1338 -47]

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CDDP induces p53-dependent apoptosis in tongue cancer cells.

Cited by 10 publications

References 0 publications

Usefulness of combined treatment with mild temperature hyperthermia and/or tirapazamine in the treatment of solid tumors: its independence of p53 status

Usefulness of combined treatment with mild temperature hyperthermia and/or tirapazamine in the treatment of solid tumors: its independence of p53 status

Aqueous Extract of Curcuma aromatica Induces Apoptosis and G2/M Arrest in Human Colon Carcinoma LS-174-T Cells Independent of p53

Luteolin sensitizes the anticancer effect of cisplatin via c-Jun NH2-terminal kinase–mediated p53 phosphorylation and stabilization

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