Abstract
The study aimed to evaluate cytotoxicity and antitumor activity of perillaldehyde 1,2-epoxide (PE), a p-menthane monoterpene derivative against four human tumor cell lines ovarian cancer (OVCAR-8), colon carcinoma (HCT-116), glioblastoma (SF-295) and leukemia (HL-60) using the colorimetric MTT assay. PE showed a high degree of inhibition of cell proliferation (GI = 95.66 to 99.71%) and IC50 16.14 μM (± 1.86), 23.61 μM (± 1.13), 21.99 μM (± 2.64) and, 9.70 μM (± 1.01) against tumor cells, respectively. Then, in vivo antitumor activity of the PE was assessed in sarcoma 180-bearing mice. Tumor growth inhibition rates were 33.4, 56.4 and 66.6% at doses of 100 and 200 mg/kg/day for the PE and 25 mg/kg/day for 5-FU intraperitoneal treatments, respectively. Toxicological effects related to the spleen, kidneys, liver, and hematological were investigated in mice submitted to treatment. Furthermore, histopathological analyses of these organs were absent of any morphological changes in the animals treated with PE. The viability of HL-60 cells was affected by perillaldehyde 1, 2-epoxide after an exposure period of 72 h when analyzed by trypan blue exclusion. PE reduced the number of viable cells associated with an increase in non-viable cells, which contributes to the increased number of dead cells in the morphological analysis. The incorporation of ethidium bromide/acridine orange, the treated cells suggests cytotoxicity via apoptosis and necrosis. So on the results, we conclude that PE presents cytotoxic and antitumoral activity through apoptotic and necrotic processes. Key words: Essential oils, p-menthanes, natural products, cytotoxicity, antitumor activity, sarcoma 180.  
Highlights
Cancer is the second most common cause of death in the world, surpassed only by cardiovascular disease and is known as malignant tumor characterized by abnormal growth and proliferation of cells (Amaral et al, 2015; Polu et al, 2015)
Compounds of natural origin have provided new and potential leads to cancer chemotherapy, and many of them are the drug of choice in cancer treatment (Polu et al, 2015)
When comparing the PC group to the groups treated with test compound, statistical alterations were observed for the groups 25, 50 and 100 mg/kg/day (p < 0.05) and no statistically significant changes for the group 200 mg/kg/day (p > 0.05). These results indicate that dose of 100 and 200 mg/kg/day the perillaldehyde 1,2-epoxide has antitumor activity in vivo against the sarcoma 180 with more significant action at the highest dose
Summary
Cancer is the second most common cause of death in the world, surpassed only by cardiovascular disease and is known as malignant tumor characterized by abnormal growth and proliferation of cells (Amaral et al, 2015; Polu et al, 2015). It is a frightful disease because the patient suffers pain, disfigurement, and loss of many physiological processes. Natural source products have offered many useful anticancer agents in current use, such as the plant-derived drugs vinblastine, irinotecan, topotecan, etoposide, and paclitaxel (Bhanot et al, 2011; Qurishi et al, 2011)
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