Traditional Chinese Medicines as Effective Reversals of Epithelial-Mesenchymal Transition Induced-Metastasis of Colorectal Cancer: Molecular Targets and Mechanisms

Abstract

Colorectal cancer (CRC) is the third most common type of cancer worldwide. Distant metastasis is the major cause of cancer-related mortality in patients with CRC. Epithelial-mesenchymal transition (EMT) is a critical process triggered during tumor metastasis, which is also the main impetus and the essential access within this duration. Therefore, targeting EMT-related molecular pathways has been considered a novel strategy to explore effective therapeutic agents against metastatic CRC. Traditional Chinese medicines (TCMs) with unique properties multi-target and multi-link that exert their therapeutic efficacies holistically, which could inhibit the invasion and metastasis ability of CRC cells via inhibiting the EMT process by down-regulating transforming growth factor-β (TGF-β)/Smads, PI3K/Akt, NF-κB, Wnt/β-catenin, and Notch signaling pathways. The objective of this review is to summarize and assess the anti-metastatic effect of TCM-originated bioactive compounds and Chinese medicine formulas by mediating EMT-associated signaling pathways in CRC therapy, providing a foundation for further research on the exact mechanisms of action through which TCMs affect EMT transform in CRC.

Clinical characteristics and survival outcomes in patients aged 75 years or older with advanced colorectal cancer treated using traditional Chinese medicine: an observational retrospective study

“…TCM is an independent factor affecting PFS (11); when combined with chemotherapy and cetuximab or bevacizumab, TCM has been shown to prolong Frontiers in Pharmacology frontiersin.org liver by down-regulating the activation of cancer-associated fibroblasts mediated by CRC-derived ITGBL1-loaded extracellular vesicles (Li et al, 2022); thus, TCM has the unique characteristics of being multi-targeted and multi-linked, and may have a comprehensive therapeutic effect. TCM can also inhibit epithelial-mesenchymal transition by downregulating transforming growth factor-beta, thereby inhibiting invasion and metastasis of CRC cells (Ge et al, 2022), inhibit progression of CRC by suppressing CCL2 and preserving progenitor Tex in an obese microenvironment (Xu et al, 2022) and suppress growth and metastasis of 5-fluorouracil-sensitive/resistant CRC by inhibiting the Wnt singling pathway (Zhang et al, 2022).…”

Integrative analysis and identification of key elements and pathways regulated by Traditional Chinese Medicine (Yiqi Sanjie formula) in colorectal cancer

“…TCM is effective in the treatment of CRC and can potentially delay cancer recurrence and suppress metastasis ( Ge et al, 2022 ). We previously showed that YQSJ formula in combination with mFOLFOX6 postoperative adjuvant chemotherapy improves the survival rate of advanced CRC patients and decreases the incidence of side effects ( Zhang et al, 2015 ; Zheng et al, 2022 ).…”

Phytochemicals as Chemo-Preventive Agents and Signaling Molecule Modulators: Current Role in Cancer Therapeutics and Inflammation

“…The transcriptional factors that control cell proliferation, survival, and migration are activated when the Wnt protein binds to frizzled family transmembrane receptors, and β-catenin accumulates in the nucleus [ 44 ]. Activation of glycogen synthase kinase 3 (GSK3) is responsible for the effects of curcumin, resveratrol, and EGCG on β-catenin translocation and accumulation in the nucleus [ 43 , 45 , 46 , 47 , 48 ]. Similarly, p53 is responsible for anticancer activity in cells, similar to other signaling pathways.…”