Open AccessInhibition of p53 Protein Phosphorylation by 9‐Hydroxyellipticine: A Possible Anticancer Mechanism
Author(s) -
Ohashi Motoaki,
Sugikawa Emiko,
Nakanishi Noriyuki
Publication year - 1995
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1995.tb03091.x
Subject(s) - phosphorylation , apoptosis , protein kinase a , kinase , lewis lung carcinoma , cancer research , biology , growth inhibition , mutant , cytotoxic t cell , cancer cell , protein phosphorylation , chemistry , cell culture , cancer , biochemistry , gene , in vitro , genetics , metastasis
Abnormality of p53, a tumor suppressor gene, is considered to be a potential cause of malignancy. We found that ellipticine and 9‐hydroxyellipticine (9HE), antitumor alkaloids, caused selective inhibition of p53 protein phospborylation in Lewis lung carcinoma and SW480 (human colon cancer cell line) in a concentration‐dependent manner from 0.1 to 100 μM . 9HE suppressed cdk2 kinase activity concentration‐dependently from 1 to 100 μM . By contrast, the inhibition of p53 protein phosphorylation by elliptinium and elliprabin (N2 substituted derivatives of 9HE) was very weak. A good correlation was observed between p53 phosphorylation inhibition and cytotoxic activity of these agents in terms of concentration‐response relationships, suggesting that inhibition of p53 protein phosphorylation via kinase inhibition may be involved in the anticancer mechanism of these agents. In addition, this study demonstrated that brief exposure to 9HE caused apoptosis of cancer cells. It is suggested that accumulation of dephosphorylated mutant p53 may induce apoptosis.