Potent in Vitro Anticancer Activity of Metacycloprodigiosin and Undecylprodigiosin from a Sponge-Derived Actinomycete Saccharopolyspora sp. nov.

  • Liu, Rui (Key Laboratory of Marine Drugs, Chinese Ministry of Education, Institute of Marine Drugs and Food, Ocean University of China) ;
  • Cui, Cheng-Bin (Beijing Institute of Pharmacology and Toxicology) ;
  • Duan, Lin (Key Laboratory of Marine Drugs, Chinese Ministry of Education, Institute of Marine Drugs and Food, Ocean University of China) ;
  • Gu, Qian-Qun (Key Laboratory of Marine Drugs, Chinese Ministry of Education, Institute of Marine Drugs and Food, Ocean University of China) ;
  • Zhu, Wei-Ming (Key Laboratory of Marine Drugs, Chinese Ministry of Education, Institute of Marine Drugs and Food, Ocean University of China)
  • Published : 2005.12.01

Abstract

Bioassay-guided fractionation of $CHCl_{3}$ extract from the fermentation broth of a sponge Mycale plumose-derived actinomycete Saccharopolyspora sp. nov., led to the isolation of two known prodigiosin analogs - metacycloprodigiosin (1) and undecylprodigiosin (2). These compounds exhibited significant cytotoxic activities against five cancer cell lines: P388, HL60, A-549, BEL­7402, and SPCA4. This is the first report on the significant cytotoxicity of metacycloprodigiosin (1) against human cancer cell lines.

Keywords

References

  1. Ricardo, P. Z., Beatriz, M., Esther, L., and Vanessa, S. C., The prodigiosins, proapoptotic drugs with anticancer properties. Biochem. Pharmacol., 66, 1447-1452 (2003) https://doi.org/10.1016/S0006-2952(03)00496-9
  2. Furstner, A., Grabowski, J., Lehmann, C. W., Kataoka, T. T., and Nagai, K., Synthesis and biological evaluation of nonylprodigiosin and macrocyclic prodigiosin analogues. Chem. Bio. Chem., 2, 60-68 (2001) https://doi.org/10.1002/1439-7633(20010105)2:1<60::AID-CBIC60>3.0.CO;2-P
  3. Nakamura, A., Nagai, K., Ando, K., and Tamura, G., Selective suppression by prodigiosin of the mitogenic response of murine splenocytes. J. Antibiot., 39, 1155-1159 (1986) https://doi.org/10.7164/antibiotics.39.1155
  4. Spongia, S., Mortellaro, A., Taverna, S., Fornasiero, C., Sheiber, E., A., Erba, E., Colotta, F., Mantovani, A., Isetta, A. M., and Golay, J., Characterization of the new immunosuppressive drug undecylprodigiosin in human lymphocytes: retinoblastoma protein, cyclin-dependent kinase-2, and cyclin-dependent kinase-4 as molecular targets. J. Immunol., 158, 3987-3995 (1997)
  5. Matsuya, H., Okamoto, M., Ochi, T., Nishikawa, A., Shimizu, S., Kataoka, T., Nagai, K., Wasserman, H. H., and Ohkuma, S., Reversible and potent uncoupling of hog gastric ($H^{+}\;+\;K^{+}$)- ATPase by prodigiosins. Biochem. Pharmacol., 60, 1855- 1863 (2000) https://doi.org/10.1016/S0006-2952(00)00509-8
  6. Sato, T., Konno, H., Tanaka, Y., Kataoka, T., Nagai, K., Wasserman, H. H., and Ohkuma, S., Prodigiosins as a new group of $H^{+}/Cl^{-}$ symporters that uncouple proton translocators. J. Biol. Chem., 273, 21455-21462 (1998) https://doi.org/10.1074/jbc.273.34.21455
  7. Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J., Vistica, D., Warren, J. T., Bokesch, H., Kenney, S., and Boyd, M. R., New colorimetric cytotoxicity assay for anticancer drug screening. J. Natl. Cancer Inst., 82, 1107-1112 (1990) https://doi.org/10.1093/jnci/82.13.1107
  8. Wasserman, H. H., Rodgers, G. C., and Keith, D. D., Metacycloprodigiosin, a tripyrrole pigment from Streptomyces longisporus ruber. J. Am. Chem. Soc., 91, 1263-1264 (1969a) https://doi.org/10.1021/ja01033a065
  9. Wasserman, H. H., Keith, D. D., and Rodgers, G. C., The structure of metacycloprodigiosin. Tetrahedron, 32, 1855- 1861 (1976b) https://doi.org/10.1016/0040-4020(76)85186-1