Abstract
Maytenus disticha (Hook F.), belonging to the Celastraceae family, is an evergreen shrub, native of the central southern mountains of Chile. Previous studies demonstrated that the total extract of M. disticha (MD) has an acetylcholinesterase inhibitory activity along with growth regulatory and insecticidal activities. β-Dihydroagarofurans sesquiterpenes are the most active components in the plant. However, its activity in cancer has not been analyzed yet. Here, we demonstrate that MD has a cytotoxic activity on breast (MCF-7), lung (PC9), and prostate (C4-2B) human cancer cells with an IC50 (µg/mL) of 40, 4.7, and 5 µg/mL, respectively, an increasing Bax/Bcl2 ratio, and inducing a mitochondrial membrane depolarization. The β-dihydroagarofuran-type sesquiterpene (MD-6), dihydromyricetin (MD-9), and dihydromyricetin-3-O-β-glucoside (MD-10) were isolated as the major compounds from MD extracts. From these compounds, only MD-6 showed cytotoxic activity on MCF-7, PC9, and C4-2B with an IC50 of 31.02, 17.58, and 42.19 µM, respectively. Furthermore, the MD-6 increases cell ROS generation, and MD and MD-6 induce a mitochondrial superoxide generation and apoptosis on MCF-7, PC9, and C4-2B, which suggests that the cytotoxic effect of MD is mediated in part by the β-dihydroagarofuran-type that induces apoptosis by a mitochondrial dysfunction.
Highlights
Cancer is one of the leading causes of morbidity and mortality worldwide
Thereafter, attention was paid to another member of this genus, Maytenus disticha, which grow near the central southern mountains of Chile, gathering 7.0 kg of aerial parts
We showed that M. disticha (MD) has cytotoxic activity against human cancer cells, inducing mitochondrial membrane depolarization and activity [11]
Summary
Cancer is one of the leading causes of morbidity and mortality worldwide. Lung, breast, and prostate cancer represent more than 32% of total cancer [1]. Some dihydroagarofuran-type sesquiterpenes, from plants of the Maytenus genus, showed an insecticidal and trypanocidal activity by producing mitochondrial dysfunction and ROS generation [16,17]. In this sense, mitochondrial dysfunction and elevated oxidative stress have been described as differentiating characteristics of cancer cells compared to normal cells [18]. We hypothesize that the total extract of Maytenus disticha and the compounds isolated from this plant have cytotoxic activity against prostate, breast, and lung cancer cells through the induction of a ROS-mediated mitochondrial dysfunction
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