Open AccessSimaomicin α, a polycyclic xanthone, induces G 1 arrest with suppression of retinoblastoma protein phosphorylation
Author(s) -
Koizumi Yukio,
Tomoda Hiroshi,
Kumagai Ayako,
Zhou Xiaoping,
Koyota Souichi,
Sugiyama Toshihiro
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.01033.x
Subject(s) - cell cycle , xanthone , jurkat cells , retinoblastoma protein , retinoblastoma , apoptosis , cell cycle checkpoint , cell growth , biology , fragmentation (computing) , phosphorylation , cell , cell culture , dna damage , chemistry , microbiology and biotechnology , cancer research , biochemistry , immunology , dna , t cell , genetics , ecology , botany , immune system , gene
Recent progress in cancer biology research has shown that abnormal proliferation in tumor cells can be attributed to aberrations in cell cycle regulation, especially in G 1 phase. During the course of searching for microbial metabolites that affect cell cycle distribution, we have found that simaomicin α, a polycyclic xanthone antibiotic, arrests the cell cycle at G 1 phase. Treatment of T‐cell leukemia Jurkat cells with 3 nM simaomicin α induced an increase in the number of cells in G 1 and a decrease in those in G 2 –M phase. Cell cycle aberrations induced by simaomicin α were also detected in colon adenocarcinoma HCT15 cells. Simaomicin α had antiproliferative activities in various tumor cell lines with 50% inhibitory concentration values in the range of 0.3–19 nM. Furthermore, simaomicin α induced an increase in cellular caspase‐3 activity and DNA fragmentation, indicating that simaomicin α promotes apoptosis. The retinoblastoma protein phosphorylation status of simaomicin α‐treated cell lysate was lower than that of control cells, suggesting that the target molecule of simaomicin α is in a pathway upstream of retinoblastoma protein phosphorylation. In the course of evaluating polycyclic xanthone antibiotics structurally related to simaomicin α, we also found that cervinomycin A1 stimulated accumulation of treated cells in G 1 phase. These results indicate that the polycyclic xanthones, including simaomicin α and cervinomycin A1, may be candidate cancer chemotherapeutic agents. ( Cancer Sci 2009; 100: 322–326)