D-limonene possesses cytotoxicity to tumor cells but not to hepatocytes

Abstract

Introduction: K562, human chronic myeloid leukemia cell line shows presence of constitutively active BCR-ABL gene. D-limonene, monoterpenes obtained from essential oils of citrus fruits have exhibited its antitumor activity in various types of cancers. Murine xenograft models are used for estimation of in vivo effect of D-limonene in K562 tumor xenograft model. Aim: The aim of present study was to evaluate the in vitro and in vivo effect of D-limonene on primary hepatocytes and K562 tumor implanted C57BL/6 mice respectively. Material and methods: Effect of D-limonene on growth of K562 cells and mouse primary hepatocytes was determined in vitro by MTT assay. The in vivo effect of D-limonene was also determined on chemically immunocompromised K562 tumor xenografted C57BL/6 mice. Results and discussion: In vitro dose dependent and time dependent studies of D-limonene shows significant reduction in viability of K562 cells. Dose dependent studies of doxorubicin and D-limonene treatment for 48 h shows significant reduction in viability of primary hepatocytes with doxorubicin whereas, the reduction was non significant with D-limonene. D-limonene treatment for 14 days also shows dose dependent reduction in tumor volume in K562 tumor xenograft C57BL/6 mice. Conclusions: D-limonene inhibited the growth of primary hepatocytes in-vitro and also inhibited in vivo K562 tumor growth in C57BL/6 mice, which suggests safety and efficacy of D-limonene in the treatment of chronic myeloid leukemia.