Pentagalloyl Glucose‐ and Ethyl Gallate‐Rich Extract from Maprang Seeds Induce Apoptosis in MCF‐7 Breast Cancer Cells through Mitochondria‐Mediated Pathway

Abstract

Bouea macrophylla Griffith, locally known as maprang, has important economic value as a Thai fruit tree. The maprang seed extract (MPSE) has been shown to exhibit antibacterial and anticancer activities. However, the bioactive constituents in MPSE and the molecular mechanisms underlying these anticancer activities remain poorly understood. This study aims to identify the active compounds in MPSE and to investigate the mechanisms involved in MPSE-induced apoptosis in MCF-7 treated cancer cells. The cytotoxic effect was determined by MTT assay. The apoptosis induction of MPSE was evaluated in terms of ROS production, mitochondrial membrane potential depolarization, and apoptosis-related gene expression. The compounds identified by HPLC and LC/MS analysis were pentagalloyl glucose, ethyl gallate, and gallic acid. MPSE treatment decreased cell proliferation in MCF-7 cells, and MPSE was postulated to induce G2/M phase cell cycle arrest. MPSE was found to promote intracellular ROS production in MCF-7 treated cells and to also influence the depolarization of mitochondrial membrane potential. In addition, MPSE treatment can lead to increase in the Bax/Bcl-2 gene expression ratio, suggesting that MPSE-induced apoptosis is mitochondria-dependent pathway. Our results suggest that natural products obtained from maprang seeds have the potential to target the apoptosis pathway in breast cancer treatments.

A radiosensitizer, gallotannin-rich extract from Bouea macrophylla seeds, inhibits radiation-induced epithelial-mesenchymal transition in breast cancer cells

“…MPSE treatment further increased IR-induced DNA-DSBs, as we observed an increase in γH2AX expression and the presence of γH2AX foci in the combination treatment group. A previous study showed that MPSE promotes intracellular reactive oxygen species (ROS) production and prevents cell cycle progression, leading to inhibition of proliferation and apoptosis induction in breast cancer MCF7 cells [ 14 ]. Our results suggested that pre-treatment with MPSE triggers ROS overproduction in IR-treated cells and enhances the effect of radiation on breast cancer cells via increasing IR-induced DNA damage.…”

“…A previous study showed that MPSE induced apoptosis in breast cancer cells via the mitochondrial pathway [ 14 ]. In this study, we found that the combined treatment of MPSE and IR markedly increased the apoptotic effect in breast cancer cells compared with a single treatment of IR or MPSE.…”

“…Our previous studies have identified MPSE contents by high performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS) analysis revealed that MPSE contains high amounts of active compounds 1,2,3,4–6-pentyl-O-galloyl-β-d-glucose (PGG), ethyl gallate (EG), and gallic acid (GA). Moreover, MPSE also induced cell cycle arrest and apoptosis with a prominent effect on human breast cancer cells than normal mammary epithelial MCF-10A cells [ 14 ]. Interestingly, pre-treatment with MPSE before irradiation suppressed the expression of multidrug resistance proteins in the radiation-survived population of MCF7 cells [ 15 ].…”

Pentagalloylglucose, isolated from the leaf extract of Anacardium occidentale L., could elicit rapid and selective cytotoxicity in cancer cells

“…However, consistent with our findings, previous studies undertaken using cell cultures, as we did, have shown that pentagalloylglucose could be involved in eliciting anti-cancer effects through mechanisms including pro-apoptosis, anti-proliferation, anti-angiogenesis, anti-metastasis and inhibition of glycoprotein [ 28 ]. Besides, Kantapan et al [ 29 ] recently reported that extracts containing pentagalloylglucose could promote intracellular ROS production and induce apoptosis in cancer cells, although it was not demonstrated whether those effects could be solely or partly attributed to the presence of pentagalloylglucose, as two other constituents were found to be present in the extract. Lin et al [ 30 ], who used cultured cells (HepG2, 293T, HEp-2, MRC-5) grown and treated in conditions very similar to ours (DMEM supplemented with 10% fetal calf serum, 24 h treatment, MTT assay), showed pentagalloylglucose lacked toxicity to the cells up to 50 μM but did not investigate higher concentrations.…”

Gallotannin from Bouea macrophylla Seed Extract Suppresses Cancer Stem-like Cells and Radiosensitizes Head and Neck Cancer

“…Our previous studies revealed that MPSE contains high amounts of active compounds such as 1,2,3,4-6-pentyl-O-galloyl-β-D-glucose (PGG), ethyl gallate (EG), and gallic acid (GA). MPSE induces increases in intracellular reactive oxygen species (ROS) and subsequently induces cell cycle arrest and apoptosis in human breast cancer cells [16]. A main active compound found in MPSE, PGG has been extensively studied for its anti-cancer properties.…”