Diverse effects of 9-hydroxyellipticine on the chemosensitivity of human pancreatic cancer cells harboring p53 mutations

Kazuhiro Mizumoto, Norihiro Sato, Masahiro Kusumoto, Hideaki Niiyama, Naoki Maehara, Shoko Nishio, Zhang Li, Takahiro Ogawa, Masao Tanaka

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Abstract

Recently, it has been shown that 9-hydroxyellipticine (9-HE), an antitumor alkaloid has a unique property of restoring functional wild-type (wt) p53 activity via inhibition of mutant (mt) p53 protein phosphorylation. In the present study, we investigated the effect of 9-HE on the drug sensitivity of human pancreatic cancer cells. Exposure of cells to 9-HE at a relatively low concentration of 1 μM induced almost no cell death but was sufficient to restore wt p53 activity, as evidenced by an induction of endogenous p21(WAF1/CIP1) concomitant with G1 and G2/M arrests in cell-cycle progression. Pretreatment with 1 μM 9-HE markedly enhanced cell killing when combined with cisplatin or mitomycin C. In contrast, 9-HE pretreatment protected cells from killing by 5-fluorouracil, VP-16, or vincristine. These effects of 9-HE were specific for several cell lines containing mt p53 and were not observed in p53-negative or wt p53 expressing cells. Taken together, these findings suggest that 9-HE may exert different effects on the drug sensitivity of pancreatic cancer cells displaying p53 mutations possibly through restoration of wt p53. (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish
Pages (from-to)85-94
Number of pages10
JournalCancer Letters
Volume149
Issue number1-2
DOIs
Publication statusPublished - Feb 28 2000

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Pancreatic Neoplasms
Mutation
Mitomycin
Vincristine
Etoposide
Mutant Proteins
Cell Cycle Checkpoints
9-hydroxyellipticine
Alkaloids
Fluorouracil
Pharmaceutical Preparations
Cisplatin
Cell Death
Phosphorylation
Cell Line

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Diverse effects of 9-hydroxyellipticine on the chemosensitivity of human pancreatic cancer cells harboring p53 mutations. / Mizumoto, Kazuhiro; Sato, Norihiro; Kusumoto, Masahiro; Niiyama, Hideaki; Maehara, Naoki; Nishio, Shoko; Li, Zhang; Ogawa, Takahiro; Tanaka, Masao.

In: Cancer Letters, Vol. 149, No. 1-2, 28.02.2000, p. 85-94.

Research output: Contribution to journalArticle

Mizumoto, K, Sato, N, Kusumoto, M, Niiyama, H, Maehara, N, Nishio, S, Li, Z, Ogawa, T & Tanaka, M 2000, 'Diverse effects of 9-hydroxyellipticine on the chemosensitivity of human pancreatic cancer cells harboring p53 mutations', Cancer Letters, vol. 149, no. 1-2, pp. 85-94. https://doi.org/10.1016/S0304-3835(99)00345-6
Mizumoto, Kazuhiro ; Sato, Norihiro ; Kusumoto, Masahiro ; Niiyama, Hideaki ; Maehara, Naoki ; Nishio, Shoko ; Li, Zhang ; Ogawa, Takahiro ; Tanaka, Masao. / Diverse effects of 9-hydroxyellipticine on the chemosensitivity of human pancreatic cancer cells harboring p53 mutations. In: Cancer Letters. 2000 ; Vol. 149, No. 1-2. pp. 85-94.
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