Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

Abstract

Tissue fibrosis and cancer both lead to high morbidity and mortality worldwide; thus, effective therapeutic strategies are urgently needed. Because drug resistance has been widely reported in fibrotic tissue and cancer, developing a strategy to discover novel targets for targeted drug intervention is necessary for the effective treatment of fibrosis and cancer. Although many factors lead to fibrosis and cancer, pathophysiological analysis has demonstrated that tissue fibrosis and cancer share a common process of epithelial‐mesenchymal transition (EMT). EMT is associated with many mediators, including transcription factors (Snail, zinc‐finger E‐box‐binding protein and signal transducer and activator of transcription 3), signaling pathways (transforming growth factor‐β1, RAC‐α serine/threonine‐protein kinase, Wnt, nuclear factor‐kappa B, peroxisome proliferator‐activated receptor, Notch, and RAS), RNA‐binding proteins (ESRP1 and ESRP2) and microRNAs. Therefore, drugs targeting EMT may be a promising therapy against both fibrosis and tumors. A large number of compounds that are synthesized or derived from natural products and their derivatives suppress the EMT by targeting these mediators in fibrosis and cancer. By targeting EMT, these compounds exhibited anticancer effects in multiple cancer types, and some of them also showed antifibrotic effects. Therefore, drugs targeting EMT not only have both antifibrotic and anticancer effects but also exert effective therapeutic effects on multiorgan fibrosis and cancer, which provides effective therapy against fibrosis and cancer. Taken together, the results highlighted in this review provide new concepts for discovering new antifibrotic and antitumor drugs.

Redox signaling in aging kidney and opportunity for therapeutic intervention through natural products

“…In the kidney, fibrosis is the pathologic extension of wound healing process response to chronic or repeated injuries, which represents a common pathway of nearly all progressive renal diseases regardless of the etiology, and may ultimately lead to architecture disruption and function loss [31,32]. Wound healing generally proceeds through three periods that are provisional overlapping but functionally distinct, including the initial inflammatory phase as well as proliferative phase and maturation phase [31,33].…”

“…In the kidney, fibrosis is the pathologic extension of wound healing process response to chronic or repeated injuries, which represents a common pathway of nearly all progressive renal diseases regardless of the etiology, and may ultimately lead to architecture disruption and function loss [31,32]. Wound healing generally proceeds through three periods that are provisional overlapping but functionally distinct, including the initial inflammatory phase as well as proliferative phase and maturation phase [31,33]. The provisional extracellular matrix exacerbated by fibrogenic cytokine undergoes degradation and facilitates tissue remodeling, the dysregulation of which or persistent chronic injury permits adequate opportunity for the formation of fibrotic lesion [34][35][36].…”

Discrimination of Different Parts of Saffron by Metabolomic‐Based Ultra‐Performance Liquid Chromatography Coupled with High‐Definition Mass Spectrometry

“…Traditional Chinese Medicine (TCM) was widely used in clinic and has been cognized an alternative therapeutic strategy for the treatment of various diseases. [1][2][3][4][5][6] Crocus sativus L. is origin from Iran and stigma is used as the medicine for activating blood circulation and eliminating stasis in China. [7] With the development of cultivation, it has been planted successfully in many countries.…”

si-SNHG5-FOXF2 Inhibits TGF-β1-induced Fibrosis in Human Primary Endometrial Stromal Cells by Wnt/β-catenin Signaling Pathway

“…IUAs are manifestations of endometrial brosis caused by factors such as trauma or infection. The main pathological changes that occur in brosis are in ammation, the production of ECM, and activation of MFs in the EMT process [17]. The annoying problem we confronted is that in clinical practice IUAs are unpredictable and thus di cult to prevent.…”

“…MFs, which exhibit characteristic of smooth muscle cells and FBs, are generally considered the key source of ECM production during tissue brosis, [12][13][14]. It has been con rmed that TGF-β1 induces the epithelial-mesenchymal transition (EMT) and causes ECM to be excessively deposited as collagen [15][16][17]. According to recent studies, Wnt/β-catenin signaling and TGF-β1 are the most powerful mediators that promote EMT; both increase the secretion of collagen and other ECM proteins by mesenchymal cells, inhibit ECM degradation and nally result in ECM deposition in damaged tissues and organs [11,18,19].…”