In Vitro Estrogenic and Breast Cancer Inhibitory Activities of Chemical Constituents Isolated from Rheum undulatum L.

Abstract

We investigated the estrogenic and breast cancer inhibitory activities of chemical constituents isolated from Rhei undulati Rhizoma (roots of Rheum undulatum L.), which is used as a laxative, an anti-inflammatory, and an anti-blood stagnation agent. Estrogen-like activity was studied using the well characterized E-screen assay in estrogen receptor (ER)-positive MCF-7 cells. The mechanism underlying the breast cancer inhibitory activity of the compounds was studied using human ER-negative MDA-MB-231 and ER-positive MCF-7 cells. The activation of apoptosis pathway-related proteins was investigated by western blotting, using extracts of R. undulatum prepared in three solvent conditions (EX1, EX2, and EX3). The R. undulatum chemical constituents (compounds 1–3) showed estrogen-like activity in the concentration range of 10 to 50 μM, by increasing the proliferation of human ER-positive MCF-7 cells. These effects were attenuated by co-treatment with 100 nM fulvestrant, an ER antagonist. Compounds 1–3 decreased the viability of MCF-7 cells in a concentration-dependent manner. Compounds 1 (aloe emodin) and 2 (rhapontigenin) induced mitochondria-independent apoptosis by activating the caspase-8 pathway, whereas the cytotoxic effect of compound 3 (chrysophanol 1-O-β-d-glucopyranoside) was mediated through the mitochondria-dependent apoptotic pathway.

4,6′-Anhydrooxysporidinone from Fusarium lateritium SSF2 Induces Autophagic and Apoptosis Cell Death in MCF-7 Breast Cancer Cells

“…The identification of effective novel therapeutic strategies remains a necessity in the treatment of breast cancer [3]. We have continually studied the effects of natural products on the apoptotic cell death of breast cancer cells [4][5][6][7][8][9]. Accumulating studies on the identification of anticancer substances from natural products have reported that apoptosis and autophagy are important pathways in the death of cancer cells [10].…”

Rheum rhaponticum and Rheum rhabarbarum: a review of phytochemistry, biological activities and therapeutic potential

“…The estrogenic activities of three other bioactive constituents of R. rhabarbarum roots (i.e. aloe-emodin, rhapontigenin and chrysophanol 1-O-b-D-glucopyranoside; 10-50 lg/ml) were also demonstrated in an experimental model of breast cancer cells (MCF-7) (Lee et al 2018).…”

“…Additionally, chrysophanol 1-O-b-D-glucopyranoside slightly stimulated the expression of proapoptotic proteins such as Bid and Bax (Trinh et al 2019). In the MCF-7 human breast cell line, aloeemodin and rhapontigenin induced the mitochondriaindependent apoptosis (mediated by the caspase-8 pathway), while chrysophanol 1-O-b-D-glucopyranoside, acted by the mitochondria-dependent apoptotic pathway (Lee et al 2018). In the same experimental model, the induction of cancer cell apoptosis was also found for desoxyrhapontigenin.…”

Aloe emodin: From antito pro-tumor action

“…Apoptosis as a result of AE treatment, depending on the type of the tumor, has been realized through the receptor-mediated or mitochondrial pathway, and regarding high correlation with oxidative stress, can be the consequence of reactive oxygen species (ROS) production. AE triggered the activation of caspase-3, -6, -7, -8 and -9, regulates the expression of numerous transcriptional factors like nuclear factor kappa B (NF-κB), p53, pro/antiapoptotic members of B-cell lymphoma-2 (Bcl-2) family etc., affecting almost all intracellular pathways involved in the realization of death program [10][11][12][13][14][15][16][17][18][19]. Intensifi ed production of ROS upon AE exposure in colon cancer cell lines induces endoplasmic reticulum stress characterized by glucose-related protein 78, phosphorylated protein kinase R-like ER kinase, phosphorylated eukaryotic initiation factor-2α expression, and increased cytosolic calcium level [17].…”