D-limonene possesses cytotoxicity to tumor cells but not to hepatocytes
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Department of Pharmacology, LM College of Pharmacy, Ahmedabad, India
Departments of Pharmacology and Toxicology, BV Patel Pharmaceutical Education and Research Development Centre, Ahmedabad, India
Anita Mehta   

Department of Pharmacology, LM College of Pharmacy, Navrangpura, Ahmedabad-380009, India. Tel.: +91 9428418611.
Online publication date: 2018-06-16
Submission date: 2017-10-06
Acceptance date: 2018-12-13
Pol. Ann. Med. 2019;26(2):98–104
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.

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.

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.

We express our deep sense of gratitude to B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre for providing facilities and encouragement to conduct the research work. The financial assistance from DST-INSPIRE for junior research fellowship to Ms. Bhavini Shah (IF 140131) is gratefully acknowledged.
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