TY  - JOUR
A1  - Gonzalez-Chavarria, Ivan
A1  - Duprat, Felix
A1  - Roa, Francisco J.
A1  - Jara, Nery
A1  - Toledo, Jorge R.
A1  - Miranda, Felipe
A1  - Becerra, Jose
A1  - Inostroza, Alejandro
A1  - Kelling, Alexandra
A1  - Schilde, Uwe
A1  - Heydenreich, Matthias
A1  - Paz, Cristian
T1  - Maytenus disticha extract and an isolated β-Dihydroagarofuran induce mitochondrial depolarization and apoptosis in human cancer cells by increasing mitochondrial reactive oxygen species
JF  - Biomolecules
N2  - 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. beta-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 (mu g/mL) of 40, 4.7, and 5 mu g/mL, respectively, an increasing Bax/Bcl2 ratio, and inducing a mitochondrial membrane depolarization. The beta-dihydroagarofuran-type sesquiterpene (MD-6), dihydromyricetin (MD-9), and dihydromyricetin-3-O-beta-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 mu M, 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 beta-dihydroagarofuran-type that induces apoptosis by a mitochondrial dysfunction.
KW  - Maytenus disticha
KW  - beta-dihydroagarofuran-type sesquiterpene
KW  - dihydromyricetin
KW  - dihydromyricetin-3-O-beta-glucoside
KW  - cytotoxic
KW  - activity
KW  - Mitochondrial ROS
Y1  - 2020
U6  - https://doi.org/10.3390/biom10030377
SN  - 2218-273X
VL  - 10
IS  - 3
PB  - MDPI
CY  - Basel
ER  -