Abstract
As a multifactorial disease, treatment of cancer depends on understanding unique mechanisms involved in its progression. The cancer stem cells (CSCs) are responsible for tumor stemness and by enhancing colony formation, proliferation as well as metastasis, and these cells can also mediate resistance to therapy. Furthermore, the presence of CSCs leads to cancer recurrence and therefore their complete eradication can have immense therapeutic benefits. The present review focuses on targeting CSCs by natural products in cancer therapy. The growth and colony formation capacities of CSCs have been reported can be attenuated by the dietary agents. These compounds can induce apoptosis in CSCs and reduce tumor migration and invasion via EMT inhibition. A variety of molecular pathways including STAT3, Wnt/β-catenin, Sonic Hedgehog, Gli1 and NF-κB undergo down-regulation by dietary agents in suppressing CSC features. Upon exposure to natural agents, a significant decrease occurs in levels of CSC markers including CD44, CD133, ALDH1, Oct4 and Nanog to impair cancer stemness. Furthermore, CSC suppression by dietary agents can enhance sensitivity of tumors to chemotherapy and radiotherapy. In addition to in vitro studies, as well as experiments on the different preclinical models have shown capacity of natural products in suppressing cancer stemness. Furthermore, use of nanostructures for improving therapeutic impact of dietary agents is recommended to rapidly translate preclinical findings for clinical use.
Highlights
The cancer is the second leading cause of death worldwide after cardiovascular diseases [1]
The cancer stem cells (CSCs) features in lung cancer mainly depend on upregulation of β-catenin and its inhibition suppresses lung tumor progression
An experiment has shown that epigallocatechin 3-gallate (EGCG) (0–100 μM) inhibits Wnt/βcatenin axis to impair CSC features in lung cancer [169]
Summary
The cancer is the second leading cause of death worldwide after cardiovascular diseases [1]. Immunotherapy is a new emerging therapeutic modality in cancer and uses checkpoint inhibitors in impairing cancer progression [10,11,12] Another strategy is tumor treatment is chemotherapy that is most common compared to other modalities, but resistance and adverse impacts reduce its potential [13,14]. The plant derived-natural products have been under attention in recent years in field of cancer therapy [31,32,33] These agents have great therapeutic activities that anti-tumor activity is among them [34,35]. Clinical trials have shown that plant derived-natural products are generally well-tolerated in cancer patients [43,44] They can be extracted for developing commercialized drugs in cancer therapy [45]. We mechanistically discuss how each phytochemical can be beneficial in cancer suppression via targeting CSCs
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