Cell Viability and Flow Cytometry Analysis of a Novel Antitumor Agent, Heptaplatin in Human Melanoma Cell Line, SK-MEL-28

신규항암제인 Heptaplatin의 인체 흑색종세포(SK-MEL-28)에 대한 세포생존률 및 유세포 분석

  • 최수라 (충남대학교 약학대학 임상생화학실) ;
  • 명평근 (충남대학교 약학대학 임상생화학실)
  • Published : 2003.12.01


Heptaplatin, cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II), is a novel platinum-based antitumor agent with clinical potential against human stomach cancer and the 3rd generation of the cisplatin. This study was performed to study how cisplain, heptaplatin and sunpla which is a mixture of heptaplatin and mannitol (w: w=l : 2) affect cell viability of SK-MEL-28 human melanoma cell line. Heptaplatin ($IC_{50}$/; 95.35 $\mu$M) and sunpla ($IC_{50}$/; 10.95 11M) were less effect than cisplatin (IC $_{50}$; 10.92 $\mu$M) on the SK-MEL-28 cells. By cell cycle analysis using flow cytometry, it was identified that the cells were arrested at G2/M phase by cisplatin, heptaplatin and sunpla, and percentage of cell death group was increased according to increasing of time and concentration. These results suggest that cisplatin, heptaplatin and sunpla are a novel anticancer agent against human melanoma cell.l.



  1. Kaufmann, S. H. : Induction of endonucleolytic DNA cleavagein human acute myelogenous leukemia cells by etoposide, camptoyhecin, and other cytotoxic anticancer drugs : acautionary note. Cancer Res. 49, 5870 (1989)
  2. Barry, M. A., Behnke, C. A. and Eastman, A. : Activation of programmed cell death (apoptosis) by cisplatin, other anti-cancer drugs, toxins and hyperthermia. Biochem. Pharmacol. 40, 2353 (1990) https://doi.org/10.1016/0006-2952(90)90733-2
  3. O'Connor, P. M., Wastermann, K., Sarang, M., Magrath, I., Bohr, V. A. and Kohn,K W. : Relationship between DNA cross-links, cell cycle, and apoptosis in Burkitt's lymphoma cell lines differing in sensitivity to nitrogen mustard. Cancer Res. 51, 6550 (1991)
  4. Miyashita, T. and Reed, J. C. : Blood 81, 151 (1993)
  5. Kim, D.-K., Kim, C., Gam,J., Cho, Y.-B., Hong, w.-S. and Park, J.-G. : J Medicinal Chemistry 37, 1471 (1994)
  6. Loehrer, P. J. and Einhorn, L. H. : Drugs five years later. cisplatin. Ann. Inter. Med. 100, 704 (1984)
  7. Ozols, R. E. and Young, R. C. : Chemotherapy of ovarian cancer. Semin. Oncol. 11, 251 (1984)
  8. Fiorentino, M. V. and Ghiotto, C. : Platinum, the synergistic drug, from clinical evidence to laboratory suggestions. in platinum and other metal coordination compounds in cancer chemotherapy;Nicolini, M., Ed., Martinus Nijhoff Publishing. Boston 415 (1988)
  9. Choksi, A. and Hong, W. K : Chemotherapy of head and neck cnacer. Boston 375 (1988)
  10. Paccagnella, A., Favaretto, G. and Fiorentino, M. V. : Chem-otherapy of lung cnacer. Boston 394 (1988)
  11. Wagener, D. J., Yap, S. H., Wobbes, T., Burghouts, J. T., van Dam, F E., Hillem, H. E, Hoogendooorn, G. J., Scheerder, H. and van der Vert, S. G. : Phase II trial of 5-fluorouracil, adriamycin and cisplatin (FAP) in advanced gastric cancer.Cancer Chemother. Pharmacol. 15, 86 (1985)
  12. Prestayko, A. w., Crooke, S. T. and Carter, S. K, Eds. : Academic Press. Ins.New York, 317 (1980)
  13. Von Hoff, D. D., Schilsky, R, Reichert, C. M., Reddick, R. L., Rozencweig, M., Young, R C. and Muggia, F. M. : Toxic effects of cis-dichlorodiammineplatinum (II) in man. Cancer Treat. Rep. 63, 1527 (1979)
  14. Krakoff, I. H. : Nephrotoxicity of cis-dichlorodiammine-platinum (II). Cancer Treat. Rep. 63, 1523 (1979)
  15. Iahibiki, K, Kumai, K., Kodaira, S., Abe, O., Yamamoto, K., Oodchi, T., Fukaya,Y., Kimura, K., Takamatsu, K., Ootsuka, E., Sakabe, T., Nishiyama, K., Sekizawa, Y., Ooide, N., Tsuchiya, S., Togo, S., Ishida, T., Mishima, Y., Ogoshi, K and Mitomi., T. : Phase II study with cisplatin in dvanced stomach and colon carcinoma. Jpn. J Cancer Chemother. 16, 3185 (1989).
  16. Hong, W. S., Saijo, N., Sasaki, Y., Minato, K., Nakano, H., Nakagawa, K., Fujiwara, Y., Nomura, K. and Twentyman, P. R. : Establishment and characterization of cisplatin-resistant sub-lines of human lung cancer lines. Int. J. Cancer 41, 462 (1988)
  17. Inoue, K., Mukaiyama, T., Mitsui, I. and Ogawa, M. : In vitro evaluation of anticancer drugs in relation to development of drug resistance in the human tumor clonogenic assay. Cancer Chemother. Pharmacol. 15, 208 (1985)
  18. Ozols, R. E : Pharmacologic rebersal of drug resistance in ovarian cancer. Semin. Oncol. 12, 7 (1985)
  19. Kim, D. K., Kim, H. T., Cho, Y. B., Tai, T. H., Ahn, J. S., Kim, T. S., Kim, K. H. and Hong, W. S. : Antitumor activity of cis-malonato[(4R,5R)-4,5-bis(aminome-thyl)-2-isopropy1-1,3-dioxolane]platinum (II), a new platinum analogue, as an anticancer agent. Cancer Chemother Pharmacl. 35, 441 (1995). https://doi.org/10.1007/s002800050260
  20. Glotzer, M. : Cyclin is degraded by the ubiquitin pathway. Nature 349, 132 (1991) https://doi.org/10.1038/349132a0