(1)
Cisplatin (CDDP) is used in
melanoma chemotherapy, but it has many side effects. Hence, the search for natural substances that can reduce the dose of CDDP, and CDDP-related toxicity, is highly desired.
Coumarins have many biological properties, including anticancer and antiproliferative effects. (2) An in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium
bromide (MTT) assay on two human
melanoma cell lines (FM55P and FM55M2) examined the antitumor properties of CDDP and five naturally occurring
coumarins (
osthole,
xanthotoxin,
xanthotoxol,
isopimpinellin, and
imperatorin). The antiproliferative effects produced by combinations of CDDP with the
coumarins were assessed using type I isobolographic analysis. (3) The most potent anticancer properties of
coumarins were presented by
osthole and
xanthotoxol. These compounds were characterized by the lowest median inhibitory concentration (IC50) values relative to the FM55P and FM55M2
melanoma cells. Isobolographic analysis showed that for both
melanoma cell lines, the combination of CDDP and
osthole exerted synergistic and additive interactions, while the combination of CDDP and
xanthotoxol exerted additive interactions. Combinations of CDDP with
xanthotoxin,
isopimpinellin, and
imperatorin showed antagonistic and additive interactions in two
melanoma cell lines. (4) The combination of CDDP and
osthole was characterized by the most desirable synergistic interaction. Isobolographic analysis allows the selection of potential candidates for
cancer drugs among natural substances.