Targeting cancer stem cells and signalling pathways through phytochemicals: A promising approach against colorectal cancer.

Wenhao Liao, Lanlan Zhang, Xian Chen, Juyi Xiang, Qiao Zheng, Nianzhi Chen, Maoyuan Zhao, Gang Zhang, Xiaolin Xiao, Gang Zhou, Jinhao Zeng, Jianyuan Tang

Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology 2022;108():154524

PMID: 36375238

Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

Cancer stem cells (CSCs) are strongly associated with high tumourigenicity, chemotherapy or radiotherapy resistance, and metastasis and recurrence, particularly in colorectal cancer (CRC). Therefore, targeting CSCs may be a promising approach. Recently, discovery and research on phytochemicals that effectively target colorectal CSCs have been gaining popularity because of their broad safety profile and multi-target and multi-pathway modes of action.

PURPOSE

This review aimed to elucidate and summarise the effects and mechanisms of phytochemicals with potential anti-CSC agents that could contribute to the better management of CRC.

METHODS

We reviewed PubMed, EMBASE, Web of Science, Ovid, ScienceDirect and China National Knowledge Infrastructure databases from the original publication date to March 2022 to review the mechanisms by which phytochemicals inhibit CRC progression by targeting CSCs and their key signalling pathways. Phytochemicals were classified and summarised based on the mechanisms of action.

RESULTS

We observed that phytochemicals could affect the biological properties of colorectal CSCs. Phytochemicals significantly inhibit self-renewal, migration, invasion, colony formation, and chemoresistance and induce apoptosis and differentiation of CSCs by regulating the Wnt/β-catenin pathway (e.g., diallyl trisulfide and genistein), the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway (e.g., caffeic acid and piperlongumine), the neurogenic locus notch homolog protein pathway (e.g., honokiol, quercetin, and α-mangostin), the Janus kinase-signal transducer and activator of transcription pathway (e.g., curcumin, morin, and ursolic acid), and other key signalling pathways. It is worth noting that several phytochemicals, such as resveratrol, silibinin, evodiamine, and thymoquinone, highlight multi-target and multi-pathway effects in restraining the malignant biological behaviour of CSCs.

CONCLUSIONS

This review demonstrates the potential of targeted therapies for colorectal CSCs using phytochemicals. Phytochemicals could serve as novel therapeutic agents for CRC and aid in drug development.

Address: Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.; State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China; University of Chinese Academy of Sciences, Beijing 100049, China.; Department of Pathology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.; Center for drug evaluation, National Medical Products Administration, Beijing 100022, China.; Center for drug evaluation, National Medical Products Administration, Beijing 100022, China. Electronic address: [email protected].; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China. Electronic address: [email protected].; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China. Electronic address: [email protected].

DOI: 10.1016/j.phymed.2022.154524

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MeSH Terms: Humans, Neoplastic Stem Cells, Phytochemicals, Wnt Signaling Pathway, Apoptosis, Receptors, Notch, Colorectal Neoplasms