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Rosemary Extract Inhibits Proliferation, Survival, Akt, and mTOR Signaling in Triple-Negative Breast Cancer Cells.

ABSTRACT: Breast cancer is the most commonly diagnosed cancer in women. Triple-negative (TN) breast cancer lacks expression of estrogen receptor (ER), progesterone receptor (PR) as well as the expression and/or gene amplification of human epidermal growth factor receptor 2 (HER2). TN breast cancer is aggressive and does not respond to hormone therapy, therefore new treatments are urgently needed. Plant-derived chemicals have contributed to the establishment of chemotherapy agents. In previous studies, rosemary extract (RE) has been found to reduce cell proliferation and increase apoptosis in some cancer cell lines. However, there are very few studies examining the effects of RE in TN breast cancer. In the present study, we examined the effects of RE on TN MDA-MB-231 breast cancer cell proliferation, survival/apoptosis, Akt, and mTOR signaling. RE inhibited MDA-MB-231 cell proliferation and survival in a dose-dependent manner. Furthermore, RE inhibited the phosphorylation/activation of Akt and mTOR and enhanced the cleavage of PARP, a marker of apoptosis. Our findings indicate that RE has potent anticancer properties against TN breast cancer and modulates key signaling molecules involved in cell proliferation and survival.

SUBMITTER: Jaglanian A

PROVIDER: S-EPMC7037743 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Rosemary Extract Inhibits Proliferation, Survival, Akt, and mTOR Signaling in Triple-Negative Breast Cancer Cells.

Jaglanian Alina A Tsiani Evangelia E

International journal of molecular sciences 20200127 3

Breast cancer is the most commonly diagnosed cancer in women. Triple-negative (TN) breast cancer lacks expression of estrogen receptor (ER), progesterone receptor (PR) as well as the expression and/or gene amplification of human epidermal growth factor receptor 2 (HER2). TN breast cancer is aggressive and does not respond to hormone therapy, therefore new treatments are urgently needed. Plant-derived chemicals have contributed to the establishment of chemotherapy agents. In previous studies, ros ...[more]

PMID: 32012648

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Project description:Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with limited treatment options and a poor prognosis. TNBC exists widely reprogrammed lipid metabolism, and its metabolic-associated proteins and oncometabolites are promising as potential therapeutic targets. Dandelion (Taraxacum mongolicum) is a classical herbal medicine used to treat breast diseases based on traditional Chinese medicine theory and was reported to have antitumor effects and lipid regulatory capacities. Our previous study showed that dandelion extract was effective against TNBC. However, whether dandelion extract could regulate the lipid metabolisms of TNBC and exert its antitumor effects via interfering with lipids metabolism remained unclear. In this study, an integrated approach combined with network pharmacology and multi-omics techniques (including proteomics, metabolomics, and lipidomics) was performed to investigate the potential regulatory mechanisms of dandelion extract against TNBC. We first determined the antitumor effects of dandelion extract in vitro and in vivo. Then, network pharmacology analysis speculated the antitumor effects involving various metabolic processes, and the multi-omics results of the cells, tumor tissues, and plasma revealed the changes in the metabolites and metabolic-associated proteins after dandelion extract treatment. The alteration of glycerophospholipids and unsaturated fatty acids were the most remarkable types of metabolites. Therefore, the metabolism of glycerophospholipids and unsaturated fatty acids, and their corresponding proteins CHKA and FADS2, were considered the primary regulatory pathways and biomarkers of dandelion extract against TNBC. Subsequently, experimental validation showed that dandelion extract decreased CHKA expression, leading to the inhibition of the PI3K/AKT pathway and its downstream targets, SREBP and FADS2. Finally, the molecular docking simulation suggested that picrasinoside F and luteolin in dandelion extract had the most highly binding scores with CHKA, indicating they may be the potential CHKA inhibitors to regulate glycerophospholipids metabolisms of TNBC. In conclusion, we confirmed the antitumor effects of dandelion extract against TNBC cells in vitro and demonstrated that dandelion extract could interfere with glycerophospholipids and unsaturated fatty acids metabolism via downregulating the CHKA expression and thus inhibiting PI3K/AKT/SREBP/FADS2 axis.

Dataset Information

Rosemary Extract Inhibits Proliferation, Survival, Akt, and mTOR Signaling in Triple-Negative Breast Cancer Cells.

Publications

Rosemary Extract Inhibits Proliferation, Survival, Akt, and mTOR Signaling in Triple-Negative Breast Cancer Cells.

Similar Datasets

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