The “Big Five” Phytochemicals Targeting Cancer Stem Cells: Curcumin, EGCG, Sulforaphane, Resveratrol and Genistein

Abstract

: Cancer stem cells (CSCs) constitute a subpopulation of tumor cells that possess self-renewal and tumor initiation capacity, and the ability to give rise to the heterogeneous lineages of cancer cells that comprise the tumor. CSCs exhibit intrinsic mechanisms of resistance to virtually all conventional cancer therapeutics, allowing them to survive current cancer therapies and to initiate tumor recurrence and metastasis. Different pathways and mechanisms that confer resistance and survival of CSCs, including activation of the Wnt/β-catenin, Sonic Hedgehog, Notch, PI3K/Akt/mTOR and STAT3 signaling pathways, expression of aldehyde dehydrogenase 1 (ALDH1) and oncogenic microRNAs, and acquisition of epithelial-mesenchymal transition (EMT), have been identified recently. Certain phytochemicals, in particular curcumin, epigallocatechin-3-gallate (EGCG), sulforaphane, resveratrol and genistein have been shown to interfere with these intrinsic CSC pathways in vitro and in human xenograft mice, leading to elimination of CSCs. Moreover, recent clinical trials have demonstrated therapeutic efficacy of the five phytochemicals, alone or in combination with modern cancer therapeutics, and in various types of cancer. Since current cancer therapies fail to eradicate CSCs, leading to cancer recurrence and progression, targeting of CSCs with phytotochemicals such as curcumin, EGCG, sulforaphane, resveratrol and genistein, combined with each other and/or in combination with conventional cytotoxic drugs and novel cancer therapeutics, may offer a novel therapeutic strategy against cancer.

Rhus coriaria L. (Sumac) Demonstrates Oncostatic Activity in the Therapeutic and Preventive Model of Breast Carcinoma

“…Moreover, cancer research has shown significant anti-CSC activities of plant-derived molecules against a wide variety of cancer types [ 69 ]. It is assumed that these activities are mediated through modulation of multiple cell mechanisms/signaling processes that demand an urgent need for in-depth evaluation within oncology research [ 70 ].…”

Overcoming cancer therapeutic bottleneck by drug repurposing

“…[283][284][285] Furthermore, genistein also inhibited stemness, which is closely related to the developmental pathways including Wnt/β-catenin and GDF15, in renal and other cancers. 283,286,287 Clinical trials of genistein in cancer therapy have been conducted, including in breast cancer (NCT00244933) (NCT00290758), in breast or endometrial cancer (NCT00099008), in bladder cancer (NCT00118040), and in prostate cancer (NCT00005827). However, clinical applications of genistein are still limited due to the poor solubility and bioavailability regardless of its potential anticancer activity by drug repurposing.…”

Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/mTOR pathway: go four better to treat bladder cancer

“…Few derivatives of plant-based phytochemicals have gained prominence in the field of cancer biology because of their limited cytotoxic effects and high specificity. Among these bioactive compounds resveratrol, curcumin, quercetin, paclitexal, genistein, Epigallocatechin-3-gallate (EGCG) and several others have been investigated extensively for their antitumor properties [ 80 ]. Phytochemicals have limited side effects which make them safe for the administration as proven in animal models and cell lines.…”