title: Growth inhibitory activity of S12363, a novel vinca alkaloid derivative on human melanoma cell lines.
abstract: The growth inhibitory activity of S12363, a new antineoplastic agent which belongs to the vinca alkaloid group incorporating an amino-phosphonate (bioester of valine), was studied on six human melanoma cell lines with different phenotypic characteristics and in vitro growth rates. S12363 was compared with vinblastine (VBL), vincristine (VCR) and vindesine (VDS) using the MTT assay. Inhibition was time- and dose-dependent. Overall, IC50 values ranged from 24-6770nM and 4.6-11.6 nM for the reference drugs and for S12363 respectively, after exposure for 1 hr. All the vinca alkaloids were more active when cells were exposed continuously for 72 hrs, inhibition by S12363 was greater than the reference drugs (p < 0.05 in 15/18 comparisons). The activities of VDS and S12363 were also compared using the clonogenic assay. IC50 values ranged from 45-500 nM and 17-75 nM respectively. On a molar basis, S12363 was significantly more active than VDS (ANOVA p < 0.0001). The shape of the cell survival curve obtained with S12363 was exponential, whereas that of VDS was of the exponential-plateau type. Furthermore, survival with higher concentrations of S12363 was inversely related to cells seeded. Cell cycle analysis showed these compounds to block cells in G2+M after exposure to their respective IC50 concentrations for 1 hr. This effect was obtained using a lower S12363 concentration. In summary, S12363 proved to be 18-83 times more active than the reference drugs in the MTT and 3-11 times more active than VDS in the clonogenic assay. Its high potency and dissimilar cell survival profile indicate that this compound possesses different biological properties, and therefore merits further in vivo evaluation.
authors: Catherine Griffiths Cancer Research Laboratory, Medical Oncology Unit, Westminster Hospital, London, U.K.
authors: C
authors: C
authors: Tolis
authors: A
authors: A
authors: Photiou
authors: R S
authors: RS
authors: Camplejohn
authors: S
authors: S
authors: Retsas
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014747:Vinblastine / Q000494:pharmacology; D014748:Vinca Alkaloids / Q000494:pharmacology*; D014750:Vincristine / Q000494:pharmacology; D014751:Vindesine / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D013778:Tetrazolium Salts; D013844:Thiazoles; D014748:Vinca Alkaloids; C064005:S 12363; D014750:Vincristine; D014747:Vinblastine; C022616:thiazolyl blue; D014751:Vindesine