Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies

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.

Contribution of the Testosterone Androgen Receptor–PARD3B Signaling Axis to Tumorigenesis and Malignance of Glioblastoma Multiforme through Stimulating Cell Proliferation and Colony Formation

“…The testosterone-induced proliferation of human glioblastoma cells can partially elucidate the enhanced capability for colony formation. Using dietary agents, including flavonoids, pomegranate, carotenoids, sulforaphane, curcumin, resveratrol, berberine, and ginseng, to reduce the capacity of cancer stem cells and cancer cells to form colonies can simultaneously impair cancer stemness, induce apoptosis of cancer cells, and enhance sensitivity of tumors to chemotherapy and radiotherapy in vitro and in vivo [ 34 ]. Thus, testosterone AR–PARD3B signaling events may be involved in tumorigenesis and malignance of human GBM through regulating cell proliferation and colony formation.…”

NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition

“…Halim et al, 2019;Kashyap et al, 2021;Li, Shanmugam et al, 2015). Furthermore, phytochemicals are affordable and developing countries can utilize them in the treatment of cancer patients (Amini et al, 2021;Ashrafizadeh, Rafiei et al, 2021;Ashrafizadeh, Zarrabi, Orouei, Saberifar et al, 2021;Deldar Abad Paskeh, Asadi et al, 2021;Hashemi et al, 2021;Hussain et al, 2021;Samec et al, 2021). This section focuses on recent studies using antitumor agents in modulating NF-κB/EMT axis.…”

“…There are some reasons for selecting plant derived‐natural products that can be their low side effects, high safety profile, multitargeting capacity, and lack of drug resistance in tumor cells (Ahn, Sethi, & Aggarwal, 2008; F. Halim et al, 2019; Kashyap et al, 2021; Li, Shanmugam et al, 2015). Furthermore, phytochemicals are affordable and developing countries can utilize them in the treatment of cancer patients (Amini et al, 2021; Ashrafizadeh, Rafiei et al, 2021; Ashrafizadeh, Zarrabi, Orouei, Saberifar et al, 2021; Deldar Abad Paskeh, Asadi et al, 2021; Hashemi et al, 2021; Hussain et al, 2021; Samec et al, 2021). This section focuses on recent studies using antitumor agents in modulating NF‐κB/EMT axis.…”

The Role of Natural Products and Their Multitargeted Approach to Treat Solid Cancer

“…A study reported that genistein inhibits tumor growth and cell proliferation by downregulating the negative effect of epidermal growth factor (EGF) on the activity of forkhead box O3 (FOXO3) in a colon cancer model [ 79 ]. In addition, it is also observed that genistein reduces breast cancer stem cells (CSCs) and mammospheres by downregulating the hedgehog-signaling pathway that subsequently regulates cell proliferation, self-renewal ability, stem cell, and progenitor cell maintenance [ 80 , 81 ]. Based on the scientific studies, it is believed that genistein regulates miRNAs expression to stop cell proliferation and up-regulates miR-200 expression, also regulate the essential targets such as vimentin, zinc finger E-box binding homeobox 1 (ZEB1), and slug, which help in the epithelial-mesenchymal transition (EMT) process [ 82 , 83 ].…”