Cytostatic effect of inostamycin, an inhibitor of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG): inositol transferase, on oral squamous cell carcinoma cell lines.
Inostamycin, which was recently isolated from Streptomyces sp. MH816-AF15 as an inhibitor of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG): inositol transferase, caused a G1-phase accumulation in the cell cycle of small cell lung carcinomas. To investigate whether the cytostatic effect of inostamycin is restricted to lung carcinoma cell lines or applicable to other type of cells, we tested five oral squamous cell carcinoma (SCC) cell lines. Cell growth was suppressed in 62.5--125 ng/ml inostamycin in the culture medium in all oral cancer cell lines tested, with non-viable cells being <1%, indicating inostamycin is cytostatic on SCC cell lines. Decrease in cyclin D1 mRNA and protein expression due to the inostamycin treatment was accompanied by suppression of phosphorylated retinoblastoma susceptibility gene product (pRB-P) levels. Moreover, flow cytometric analysis showed that inostamycin induced an increase in G1/G0 cells (1.2--3.2 fold) over 24 h. These results suggest that inostamycin is a useful agent for tumour dormant cytostatic therapy for oral SCC.
Baba
Y
Y
Department of Otolaryngology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
Tsukuda
M
M
Mochimatsu
I
I
Furukawa
S
S
Kagata
H
H
Nagashima
Y
Y
Koshika
S
S
Imoto
M
M
Kato
Y
Y
D000970:Antineoplastic Agents / Q000494:pharmacology*; D051607:CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D008565:Membrane Proteins; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016376:Oligonucleotides, Antisense; D012334:RNA, Neoplasm / Q000096:biosynthesis; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000235:genetics; D017855:Transferases (Other Substituted Phosphate Groups) / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D005663:Furans; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D012334:RNA, Neoplasm; D016160:Retinoblastoma Protein; C071861:inostamycin; D019938:Cyclin D1; D017855:Transferases (Other Substituted Phosphate Groups); C496766:CDIPT protein, human; D051607:CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase