Biomedical subjects

Masashi Suganuma

Publications and source records attributed to Masashi Suganuma.

4 recordsLinked to original sources

PubMed2004

Selective inhibition of bleomycin-induced G2 cell cycle checkpoint by simaomicin alpha.

Human T-cell leukemia-derived Jurkat cells are known to be defective in the G1 checkpoint. DNA-damaging agent bleomycin arrests the cell cycle at G2 phase of Jurkat cells, and microtubule-acting colchicine arrests it at the M phase. Simaomicin alpha, an actinomycete metabolite, itself showed no effect on the cell cycle status of Jurkat cells at least up to 6.0 nM. However, the compound (0.6-6.0 nM) was found to abrogate the bleomycin-induced G2 arrest, yielding a drastic decrease in cells at the G2 phase and increase in cells at the subG1 and G1 phases. On the other hand, the compound did not show any effect on the colchicine-induced M phase arrest in Jurkat cells. Furthermore, the compound showed almost no effect on the cell cycle status of the bleomycin-treated or -untreated normal cell line HUVEC. These data suggested that simaomicin alpha disrupts the cell cycle G2 checkpoint of cancer cells selectively, leading to sensitization of cancer cells to anti-cancer reagents.

Bleomycin↗

PubMed2004

Boromycin abrogates bleomycin-induced G2 checkpoint.

The DNA-damaging agent bleomycin arrests the cell cycle at the G2 phase of Jurkat cells defective in the G1 checkpoint, and microtubule-acting colchicine arrests it at the M phase. Boromycin itself, an actinomycete metabolite, showed no effect on the cell cycle status of Jurkat cells at least up to 340 nM. However, the compound (3.4-340 nM) was found to abrogate bleomycin-induced G2 arrest even at 3.4 nM, resulting in a drastic decrease in cells at the G2 phase and increase in cells at the subG1 phase. On the other hand, boromycin did not show any effect on the colchicine-induced M phase arrest in Jurkat cells, nor on the cell cycle status of the bleomycin-treated or -untreated HUVEC, normal cells conserving both G1 and G2 checkpoints. Furthermore, boromycin potentiated anti-tumor activity of bleomycin in scid mice inoculated with Jurkat cells. These data suggest that boromycin disrupts the cell cycle at the G2 checkpoint of cancer cells selectively, leading to sensitization of cancer cells to anti-cancer reagents.

Animals↗

PubMed2002

Cdc25C interacts with PCNA at G2/M transition.

Cdc25 activates maturation promoting factor (MPF) and promotes mitosis by removing the inhibitory phosphate from the Tyr-15 of Cdc2 in human cells. In this study, we searched the interacting protein(s) of human Cdc25C using the yeast two-hybrid screen and identified proliferating cell nuclear antigen (PCNA) as an interacting partner of Cdc25C. The interaction between Cdc25C and PCNA was confirmed in vitro and in vivo. Co-immunoprecipitation analyses using human T cell line, Jurkat, further revealed that Cdc25C interacted with PCNA transiently when cells began to enter mitosis. Immunofluorescence analysis also showed that Cdc25C and PCNA were transiently co-localized in the nucleus at the beginning of M phase. Together with the previous observations of the interaction between various cdc/cyclin and PCNA, our findings strongly suggested a potential role of PCNA at the G2 to M phase transition of cell cycle.

Cell Cycle Proteins↗

PubMed2000

Gastritis cystica polyposa associated with a gastric stump carcinoma, with special reference to cell kinetics and p53 gene aberrations.

We report a case of gastritis cystica polyposa (GCP) that developed in association with a small stump carcinoma. The patient had had distal gastrectomy for peptic ulcer 33 years prior to the present illness. Total gastrectomy was carried out for the stump carcinoma of the remnant stomach, followed by Roux-en-Y anastomosis. Histological examination revealed that the cancer was associated with a GCP lesion in its neighborhood. The resected stomach was subjected to a cell kinetics study and p53 gene analysis, as GCPs are thought to have a high potential for carcinogenesis. The GCP mucosae, as well cancer tissues and remnant mucosae obtained from the same specimens, were investigated and compared. We found that cell kinetics, as measured by a Ki-67 labeling index count, was more accelerated in the GCP than in the remnant mucosa, and that p53 gene aberrations, including both mutations and deletions, took place in the GCP lesion. As the p53 gene is considered to be recessive, in principle, its tumor suppressive activity is lost only when gene aberration, either mutation or deletion, occurs concurrently or successively in both alleles. It was of interest to us that a benign lesion such as GCP had, in this instance, already developed both gene aberrations, strongly suggesting a precancerous nature for this disease.

Journal Article↗