Cassane diterpenoids and derivatives isolated from Caesalpinia pulcherrima with selective cytotoxic activity against multiple myeloma cells

Abstract

Caesalpinia pulcherrima is used ethnomedicinally for a variety of ailments. To further evaluate the biological significance of this plant, we investigated the cancer cell cytotoxic effects of the cassane diterpenoids (1 – 10) previously isolated from the root bark of the plant. The cytotoxic effects of the diterpenoids were evaluated on three cancer cell lines; cervical cancer (HeLa), lung cancer (A549), multiple myeloma (MM.1S) and the normal human embryonic kidney (HEK293T) cells using the CellTitre-Glo assay. Compounds 4, 9, and 10 were active against the three cancer cell lines (HeLa, A549, and MM.1S), and toxic to HEK293T cells, but possess the most potent activity against multiple myeloma cells. Compounds 1, 2, 8, and 10 were active against A549 and MM.1S cells while compound 7 was active against MM.1S cells only. Compound 10 was highly selective against MM.1S with IC₅₀ of 1.07 ± 0.07 µM and 7.54 ± 0.16 µM against MM.1S and HEK293T cells, respectively. In addition, compound 10 showed a significant synergistic effect with bortezomib. The present study has shown a potential of the cassane diterpenoids and their derivatives as cytotoxic agents against cancer cells particularly against multiple myeloma cells either as a single therapeutic agent or in combination with known cytotoxic drugs.