A Comparative Evaluation of the Cytotoxic and Antioxidant Activity of Mentha crispa Essential Oil, Its Major Constituent Rotundifolone, and Analogues on Human Glioblastoma.

ABSTRACT

Cancer is a major public health problem around the globe. This disorder is affected by alterations in multiple physiological processes, and oxidative stress has been etiologically implicated in its pathogenesis. Glioblastoma (GBM) is considered the most common and aggressive brain tumor with poor prognosis despite recent improvements in surgical, radiation, and chemotherapy-based treatment approaches. The purpose of this study was to evaluate antitumor activity from Mentha crispa essential oil (MCEO), its major constituent rotundifolone (ROT), and a series of six analogues on the human U87MG glioblastoma cell line. Cytotoxic effects of the compounds on the human U87MG-GBM cell line were assessed using in vitro cell viability and oxidative and molecular genetic assays. In addition, biosafety assessment tests were performed on cultured human blood cells. Our findings revealed that MCEO, 1,2-perillaldehyde epoxide (EPER1), and perillaldehyde (PALD) were the most cytotoxic compounds against U87MG cells, with IC50 values of 16.263, 15.087, and 14.888 µg/mL, respectively. Further, these compounds increased the expressions of BRAF, EGFR, KRAS, NFκB1, NFκB1A, NFκB2, PIK3CA, PIK3R, PTEN, and TP53 genes at different degrees and decreased the expression of some genes such as AKT1, AKT2, FOS, and RAF1. Finally, treatment with MCEO, EPER1, and PALD did not lead to genotoxic damage in blood cells. Taken together, our findings reveal antiproliferative potential of MCEO, its major component ROT, and its tested analogues. Some of these chemical analogues may be useful as prototypes for the development of novel chemotherapeutic agents for treating human brain cancer and/or other cancers due to their promising activities as well as nonmutagenic property and safety.