Camptothecin-induced death of amelanotic and melanotic melanoma cells in different phases of cell cycle

Abstract

Camptothecin and its analogues are used as S-phase specific antitumor drugs because of topoisomerase I inhibition providing cells to death by apoptosis. Our previous works documented that amelanotic hamster's melanoma is very sensitive to camptothecin. Because of the challenges in treating melanoma and S-phase specificity of camptothecin, we performed a study to search what melanoma cell cycle phases are susceptible to this substance. Melanotic (Ma) and amelanotic (Ab) lines of Bomirski hamster's melanoma were used. Camptothecin cytotoxicity was determined by TUNEL method and cell cycle analysis was done by DNA staining with propidium iodide. Camptothecin after short time killed amelanotic melanoma cells from S/G2/M phases but with extended time dying cells came from G0/G1. Melanotic melanoma had fewer cells in S/G2/M phases and 3-fold more of these cells spontaneously died in comparison to more aggressive amelanotic line. High susceptibility of amelanotic melanoma cells to camptothecin show that not only cells with proliferative activity were sensitive to this alkaloid but with extended time it killed cells from all cycle phases. High number of cells in S/G2/M phases and low rate of spontaneous death among amelanotic melanoma cells suggest that the expansive growth of this melanoma line depends mainly on the decreased ability to undergo spontaneous apoptosis. If the sensitivity of amelanotic melanoma is not only hamster's but also human melanoma feature, we can suspect that by choosing melanoma form for treatment with camptothecin we could improve effectiveness of this drug against melanoma.