Summary
We compared in vitro the cytotoxic activity of vinorelbine (VRB) (Navelbine, 5′-noranhydrovinblastine) a novelVinca alkaloid, with that of vinblastine (VBL) vincristine (VCR) and vindesine (VDS). Five continuous human melanoma cell lines (C32, G361, StMl11a, StMl12d and StMl14a) and a new line WHMel 1, were used in this study. In growth-inhibition assays, VDS and VRB exhibited comparable cytotoxicity against the C32 and G361 melanoma lines; the effect being dose- and time-dependent. VRB appeared less inhibitory compared to VDS in the lowest concentrations (0.1–1 nM). The same activity was observed with 0.1–1 μM. These drugs exhibited comparable growth inhibition at clinically achievable doses. The MTT assay was used to compare VBL, VCR, VDS, and VRB. Overall IC50 values (concentration required to reduce viability by 50%) ranged from 1 pM to 10 nM. The reduction in cell viability with VRB was similar to that observed with the reference drugs in four out of five lines tested by this method. However a trend was observed for IC50 values to be lower with VBL and VDS. In clonogenic assays (StMl11a, StMl12d and StMl14a lines, 1 h exposure) VRB and VDS produced the same reduction in survival. Survival curves were exponential followed by a terminal plateau. IC50 values ranged from 60 nM to 70 nM. Our results indicate that VRB has in vitro activity against six melanoma lines with differing phenotypic characteristics.
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Abbreviations
- VBL:
-
vinblastine
- VCR:
-
vincristine
- VDS:
-
vindesine
- VRB:
-
vinorelbine
- MTT:
-
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
References
Alley MC, Scudiero DA, Monks A, Hursey NL, Czerwinski MJ, Fine DL, Abbott BJ, Mayo JG, Shoemaker RH, Boyd MR (1988) Feasibility of drug screening with panels of human tumour cell lines using a microculture tetrazolium assay. Cancer Res 48:589–601
Binet S, Fellous A, Lataste H, Krikorian A, Couzinier JP, Meininger V (1989) In situ analysis of the action of Navelbine on various types of microtubules using immunofluorescence. Semin Oncol 16 [Suppl 4]:5–8
Carmichael J, Atkinson RJ, Calman KC, Mackie RN, Naysmith AAM, Smyth JE (1982) A multicentre phase II trial of vindesine in malignant melanoma. Eur J Cancer Clin Oncol 18:1293–1295
Chen TR, Shaw MW (1973) Stable chromosome changes in human malignant melanoma. Cancer Res 33:2042–2047
Cros S, Potier P (1986) Nor-anhydrovinblastine (Navelbine), a new type of anti-tumour compound of the vinblastine group. In: Barton D, Ollis WD (eds) Advances in medicinal phytochemistry (Publ) J. Libby, London, pp 139–143
Ferguson PJ, Phillips JR, Selner M, Cass CE (1984) Differential activity of Vincristine and Vinblastine against cultured cells Cancer Res 44:3307–3312
Gout PW, Noble RL, Bruchovsky N, Beer CT (1984) Vinblastine and Vincristine growth inhibitory effects correlate with their retention by cultured Nb 2 node lymphoma cells. Int J Cancer 34:245–248
Hill BT (1983) Use of continuous human tumour cell lines to evaluate drugs by clonogenic assay. In: Denby PP, Hill BT (eds) Human tumour drug sensitivity testing in vitro: techniques and clinical applications. Academic Press, London, pp 129–146
Hill BT, Whelan RDH (1981) Comparative cell killing and kinetic effects of Vincristine or Vindesine in mammalian cell lines. JNCI 67:437–443
Hill BT, Whelan RDH, Hosking LK, Ward BG, Gibby EM (1984) The value of human tumour continuous cell lines for investigating aspects of methodologies used in in vitro drug sensitivity testing. In: Salmon SE, Trent JM (eds) Human tumour cloning Grune & Stratton, New York pp 487–496
Hill BT, Whelan RDH, Hosking LK (1988) Use of human neuroblastoma continuous cell lines for in vitro drug sensitivity screening. Invest New Drugs 6:11–18
Krikorian A, Rahmani R, Bromet M, Bore P, Cano JP (1989) Pharmacokinetics and metabolism of Navelbine. Semin Oncol 16 [Suppl 4]:21–25
Langlois N, Gueritte F, Langlois Y, Potier P (1976) Application of a modification of the Polonovski reaction to the synthesis of Vinblastine-type alkaloids. J Am Chem Soc 98:7017–7024
Metcalfe SA, Whelan RDH, Masters JRW, Hill BT (1983) In vitro responses of human prostrate tumour cell lines to a range of antitumour agents. Int J Cancer 32:351–358
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63
Peebles PT, Trisch T, Popageorge AG (1978) Isolation of four unusual pediatric solid tumor cell lines (abstract). Pediatr Res 12:485
Photiou A, Bafaloukos D, Sheikh MN, Retsas S (1990) In vitro cytotoxicity of Vinorelbine (Navelbine), a novelVinca alkaloid drug, versus Vindesine, on human melanoma cell lines (abstract). Presented at 5th Scientific Meeting of the British Oncological Association. Br J Cancer 62 [Suppl 11]:25
Potier P (1989) The synthesis of Navelbine prototype of a new series of vinblastine derivatives. Semin Oncol 16:[Suppl 4]:2–4
Quagliana JM, Stephens RL, Baker LH, Costanzi JJ (1984) Vindesine in patients with metastatic malignant melanoma: a southwest Oncology Group study. J Clin Oncol 2; No 4 316–319
Rahmani RM, Bruno R, Iliadis A, Favre R, Just S, Barbet J, Cano JP (1987) Clinical pharmacokinetics of the antitumour drug Navelbine (5′-noranhydrovinblastine). Cancer Res 47:5796–5799
Retsas S, Peat I, Ashford R, et al (1980) Updated results of Vindesine as a single agent in the therapy of advance malignant melanoma. Cancer Treat Rev 7 [Suppl]:87–90
Roper PR, Drewinko B (1976) Comparison of in vitro methods to determine drug-induced cell lethality. Cancer Res 36:2182–2188
Twentyman PR (1985) Predictive chemosensitivity testing (editorial). BR J Cancer 51:295
Twentyman PR, Luscombe M (1987) A study of some variables in a tetrazolium dye (MTT) based assay for cell growth and chemosensitivity. Br J Cancer 56:279–285
Zouboulis Ch, Garbe C, Orfanos LE (1989a) Factors influencing the in vitro growth of human melanoma cell lines. Skin Cancer 4:63–72
Zouboulis Ch, Schroder K, Krasagakis K, Kruger S, Garbe C, Orfanos CE (1989b) Correlation of the tumour necrosis factor-α and the phenotype of melanoma cells in vitro (abstract). J Invest Dermatol 93:586
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Photiou, A., Sheikh, M.N., Bafaloukos, D. et al. Antiproliferative activity of vinorelbine (Navelbine) against six human melanoma cell lines. J Cancer Res Clin Oncol 118, 249–254 (1992). https://doi.org/10.1007/BF01208613
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DOI: https://doi.org/10.1007/BF01208613