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

doi:10.1016/j.phymed.2022.154524

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

Phytomedicine. 2023 Jan:108:154524. doi: 10.1016/j.phymed.2022.154524. Epub 2022 Oct 31.

Authors

Wenhao Liao¹, Lanlan Zhang², Xian Chen³, Juyi Xiang⁴, Qiao Zheng¹, Nianzhi Chen¹, Maoyuan Zhao¹, Gang Zhang¹, Xiaolin Xiao¹, Gang Zhou⁵, Jinhao Zeng⁶, Jianyuan Tang⁷

Affiliations

¹ Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
² 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.
³ Department of Pathology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
⁴ Center for drug evaluation, National Medical Products Administration, Beijing 100022, China.
⁵ Center for drug evaluation, National Medical Products Administration, Beijing 100022, China. Electronic address: jackiehk@163.com.
⁶ 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: zengjinhao@cdutcm.edu.cn.
⁷ TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China. Electronic address: tangjy@cdutcm.edu.cn.

PMID: 36375238
DOI: 10.1016/j.phymed.2022.154524

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.

Keywords: Cancer stem cells; Colorectal cancer; Phytochemicals.

Publication types

Review

MeSH terms

Apoptosis
Colorectal Neoplasms* / pathology
Humans
Neoplastic Stem Cells*
Phytochemicals / therapeutic use
Receptors, Notch / metabolism
Wnt Signaling Pathway

Substances

Phytochemicals
Receptors, Notch