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Dietary Phytochemicals Targeting Cancer Stem Cells.

ABSTRACT: There is an increasing awareness of the importance of a diet rich in fruits and vegetables for human health. Cancer stem cells (CSCs) are characterized as a subpopulation of cancer cells with aberrant regulation of self-renewal, proliferation or apoptosis leading to cancer progression, invasiveness, metastasis formation, and therapy resistance. Anticancer effects of phytochemicals are also directed to target CSCs. Here we provide a comprehensive review of dietary phytochemicals targeting CSCs. Moreover, we evaluate and summarize studies dealing with effects of dietary phytochemicals on CSCs of various malignancies in preclinical and clinical research. Dietary phytochemicals have a significant impact on CSCs which may be applied in cancer prevention and treatment. However, anticancer effects of plant derived compounds have not yet been fully investigated in clinical research.

SUBMITTER: Liskova A

PROVIDER: S-EPMC6429493 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Dietary Phytochemicals Targeting Cancer Stem Cells.

Liskova Alena A Kubatka Peter P Samec Marek M Zubor Pavol P Mlyncek Milos M Bielik Tibor T Samuel Samson Mathews SM Zulli Anthony A Kwon Taeg Kyu TK Büsselberg Dietrich D

Molecules (Basel, Switzerland) 20190304 5

There is an increasing awareness of the importance of a diet rich in fruits and vegetables for human health. Cancer stem cells (CSCs) are characterized as a subpopulation of cancer cells with aberrant regulation of self-renewal, proliferation or apoptosis leading to cancer progression, invasiveness, metastasis formation, and therapy resistance. Anticancer effects of phytochemicals are also directed to target CSCs. Here we provide a comprehensive review of dietary phytochemicals targeting CSCs. M ...[more]

PMID: 30836718

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Project description:BACKGROUND:Cell migration and invasion are essential processes for metastatic dissemination of cancer cells. Significant progress has been made in developing new therapies against oncogenic signaling to eliminate cancer cells and shrink tumors. However, inherent heterogeneity and treatment-induced adaptation to drugs commonly enable subsets of cancer cells to survive therapy. In addition to local recurrence, these cells escape a primary tumor and migrate through the stroma to access the circulation and metastasize to different organs, leading to an incurable disease. As such, therapeutics that block migration and invasion of cancer cells may inhibit or reduce metastasis and significantly improve cancer therapy. This is particularly more important for cancers, such as triple negative breast cancer, that currently lack targeted drugs. METHODS:We used cell migration, 3D invasion, zebrafish metastasis model, and phosphorylation analysis of 43 protein kinases in nine triple negative breast cancer (TNBC) cell lines to study effects of fisetin and quercetin on inhibition of TNBC cell migration, invasion, and metastasis. RESULTS:Fisetin and quercetin were highly effective against migration of all nine TNBC cell lines with up to 76 and 74% inhibitory effects, respectively. In addition, treatments significantly reduced 3D invasion of highly motile TNBC cells from spheroids into a collagen matrix and their metastasis in vivo. Fisetin and quercetin commonly targeted different components and substrates of the oncogenic PI3K/AKT pathway and significantly reduced their activities. Additionally, both compounds disrupted activities of several protein kinases in MAPK and STAT pathways. We used molecular inhibitors specific to these signaling proteins to establish the migration-inhibitory role of the two phytochemicals against TNBC cells. CONCLUSIONS:We established that fisetin and quercetin potently inhibit migration of metastatic TNBC cells by interfering with activities of oncogenic protein kinases in multiple pathways.

Dataset Information

Dietary Phytochemicals Targeting Cancer Stem Cells.

Publications

Dietary Phytochemicals Targeting Cancer Stem Cells.

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