Abstract
Pendolmycin is a new indole alkaloid isolated from Nocardiopsis as an inhibitor of phosphatidyl‐inositol turnover. Structurally, pendolmycin is similar to teleocidin B and lyngbyatoxin A. Pendolmycin, teleocidin B and 12‐O‐tetradecanoylphorbol‐13‐acetate all inhibited phosphatidylinositol turnover in A431 cells. Pendolmycin inhibited binding of epidermal growth factor, activated ara‐chidonic acid release and hexose transport, and inhibited binding of phorbol‐12,13‐tlibutylate in C3H10T1/2 cells. Thus, pendolmycin was as potent as teleocidin B and phorbol ester tumor promoters in modification of cell membrane functions, while having the simplest structure among them.
Keywords: Pendolmycin, Teleocidin, Tumor promotion, Phosphatidylinositol turnover, Epidermal growth factor
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REFERENCES
- 1. ) Yamashita , T. , Imoto , M. , Isshiki , K. , Sawa , T. , Naganawa , H. , Kurasawa , S. , Bao‐quan , Z. and Umezawa , K.Isolation of a new indole alkaloid, pendolmycin, from Nocardiopsis . J. Nat. Prod., (Lloydia) , in press . [Google Scholar]
- 2. ) Takashima , M. and Sakai , H.A news toxic substance, teleocidin, produced by Streptomyces. Part I. Production, isolation and chemical studies . Bull. Agric. Chem. Soc. Jpn. , 647 – 651 ( 1960. ). [Google Scholar]
- 3. ) Cardellina , J. H.II , Marner , F‐J. and Moore , R. E.Seaweed dermatitis: structure of lyngbyatoxin A . Science , 204 , 193 – 195 ( 1979. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Fujiki , H. and Sugimura , T.New potent tumour promoters: teleocidin, lyngbyatoxin A and aplysiatoxin . Cancer Surv. , 2 , 539 – 556 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 5. ) Umezawa , K. , Weinstein , I. B. , Horowitz , A. , Fujiki , H. , Matsushima , T. and Sugimura , T.Similarity of teleocidin B and phorbol ester tumour promoters in effects on membrane receptors . Nature , 290 , 411 – 413 ( 1981. ). [DOI] [PubMed] [Google Scholar]
- 6. ) Rodriguez‐Pena , A. and Rozengurt , E.Disappearance of Ca2+‐sensitive, phospholipid‐dependent protein kinase activity in phorbol ester‐treated 3T3 cells . Biochem. Biophys. Res. Commun. , 120 , 1053 – 1059 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Friedman , B. , Frackelton , A. R. , Jr. , Ross , A. H. , Connors , J. M , Fujiki , H. , Sugimura , T. and Rosner , M. R.Tumor promoters block tyrosine‐specific phosphorylation of the epidermal growth factor receptor . Proc. Natl. Acad. Sci. USA , 81 , 3034 – 3038 ( 1984. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. ) Imoto , M. , Umezawa , K. , Sawa , T. , Takeuchi , T. and Umezawa , H.In situinhibition of tyrosine protein kinase by erbstatin . Biochem. Int. , 15 , 989 – 995 ( 1987. ). [PubMed] [Google Scholar]
- 9. ) Geny , B. , LePeuch , C , Cost , H. , Basset , M. and Cock‐croft , S.Phorbol esters inhibit inositol phosphate and diacylglycerol formation in proliferating HL60 cells . FEBS Lett. , 233 , 239 – 243 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 10. ) Fujiki , H , Suganuma , M. , Hakii , H. , Nakayasu , M. , Endo , Y. , Shudo , K. , Irie , K. , Koshimizu , K. and Sugimura , T.Tumor promoting activities of new synthetic analogues of teleocidin . Proc. Jpn. Acad. , 61 , Ser. B , 45 – 47 ( 1985. ). [Google Scholar]
- 11. ) Fujiki , H. , Suganuma , M. , Ninomiya , M. , Yoshizawa , S. , Yamashita , K. , Takayama , S. , Hitotsuyanagi , Y. , Sakai , S. , Shudo , K. and Sugimura , T.Similar potent tumor‐promoting activity of all isomers of teleocidin A and B in a two‐stage carcinogenesis experiment on the skin of CD‐1 mouse . Cancer Res. , 48 , 4211 – 4214 ( 1988. ). [PubMed] [Google Scholar]