scholarly journals Pien Tze Huang Overcomes Multidrug Resistance and Epithelial-Mesenchymal Transition in Human Colorectal Carcinoma Cells via Suppression of TGF-βPathway

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Aling Shen ◽  
Hongwei Chen ◽  
Youqin Chen ◽  
Jiumao Lin ◽  
Wei Lin ◽  
...  

The traditional Chinese medicine formula Pien Tze Huang (PZH) has long been used as a folk remedy for cancer. To elucidate the mode of action of PZH against cancer, in the present study we used a 5-FU resistant human colorectal carcinoma cell line (HCT-8/5-FU) to evaluate the effects of PZH on multidrug resistance (MDR) and epithelial-mesenchymal transition (EMT) as well as the activation of TGF-βpathway. We found that PZH dose-dependently inhibited the viability of HCT-8/5-FU cells which were insensitive to treatment of 5-FU and ADM, demonstrating the ability of PZH to overcome chemoresistance. Furthermore, PZH increased the intercellular accumulation of Rhodamine-123 and downregulated the expression of ABCG2 in HCT-8/5-FU cells. In addition, drug resistance induced the process of EMT in HCT-8 cells as evidenced by EMT-related morphological changes and alteration in the expression of EMT-regulatory factors, which however was neutralized by PZH treatment. Moreover, PZH inhibited MDR/EMT-enhanced migration and invasion capabilities of HCT-8 cells in a dose-dependent manner and suppressed MDR-induced activation of TGF-βsignaling in HCT-8/5-FU cells. Taken together, our study suggests that PZH can effectively overcome MDR and inhibit EMT in human colorectal carcinoma cells via suppression of the TGF-βpathway.

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Kai Zhang ◽  
Tao Peng ◽  
Qingying Yan ◽  
Leitao Sun ◽  
Haojun Miao ◽  
...  

Jiedu Sangen Decoction (JSD), a traditional Chinese medicine (TCM) formula, has been widely used in China to treat gastrointestinal cancer, especially as an adjuvant therapy in colorectal cancer (CRC) patients. This study aimed to evaluate the efficacy of JSD and Jiedu Sangen aqueous extract (JSAE) in colon cancer cells and explored the underlining mechanisms by cytotoxicity assay, scratch assay, transwell migration assay, matrigel invasion assay, confocal laser scanning microscopy, and western blot analysis. We demonstrated that JSAE inhibited the growth of colon cancer SW480 cells in a dose-dependent manner and JSAE repressed cancer cell migration and invasion. Furthermore, epithelial mesenchymal transition (EMT) was reversed by JSAE via enhancing E-cadherin expression and attenuating protein levels of EMT promoting factors such as N-cadherin, Slug, and ZEB1. These findings provided the first experimental evidence confirming the efficacy of JSAE in repressing invasion and metastasis of CRC and paving a way for the broader use of JSD in clinic.


Oncotarget ◽  
2017 ◽  
Vol 8 (61) ◽  
pp. 103900-103918 ◽  
Author(s):  
Jing-Jing Wang ◽  
Qing-Yun Chong ◽  
Xin-Bao Sun ◽  
Ming-Liang You ◽  
Vijay Pandey ◽  
...  

2020 ◽  
Vol 21 (5) ◽  
pp. 1827 ◽  
Author(s):  
Yahima Frión-Herrera ◽  
Daniela Gabbia ◽  
Michela Scaffidi ◽  
Letizia Zagni ◽  
Osmany Cuesta-Rubio ◽  
...  

The majority of deaths related to colorectal cancer (CRC) are associated with the metastatic process. Alternative therapeutic strategies, such as traditional folk remedies, deserve attention for their potential ability to attenuate the invasiveness of CRC cells. The aim of this study is to investigate the biological activity of brown Cuban propolis (CP) and its main component nemorosone (NEM) and to describe the molecular mechanism(s) by which they inhibit proliferation and metastatic potential of 2 CRC cell lines, i.e., HT-29 and LoVo. Our results show that CP and NEM significantly decreased cell viability and inhibited clonogenic capacity of CRC cells in a dose and time-dependent manner, by arresting the cell cycle in the G0/G1 phase and inducing apoptosis. Furthermore, CP and NEM downregulated BCL2 gene expression and upregulated the expression of the proapoptotic genes TP53 and BAX, with a consequent activation of caspase 3/7. They also attenuated cell migration and invasion by inhibiting MMP9 activity, increasing E-cadherin and decreasing β-catenin and vimentin expression, proteins involved in the epithelial–mesenchymal transition (EMT). In conclusion NEM, besides displaying antiproliferative activity on CRC cells, is able to decrease their metastatic potential by modulating EMT-related molecules. These finding provide new insight about the mechanism(s) of the antitumoral properties of CP, due to NEM content.


2020 ◽  
Vol 19 ◽  
pp. 153473542097248
Author(s):  
Feiyu Shan ◽  
Leitao Sun ◽  
Leyin Zhang ◽  
Kaibo Guo ◽  
Qingying Yan ◽  
...  

Background: Jiedu Sangen Decoction (JSD), a traditional Chinese medicine formula, has been widely applied in the treatment of gastrointestinal cancer, especially in colorectal cancer. Our study mainly aimed to assess the combined efficacy of Jiedu Sangen aqueous extract (JSAE) and a PD-L1 inhibitor (PI) in colon cancer cells migration and invasion, along with epithelial-mesenchymal transition, and then provide deep insights into the potential mechanism. Methods: We explored the inhibitory effects on invasion and metastasis and the reverse effect on EMT process in CT-26 colon cancer cell via Transwell migration assay, Matrigel invasion assay and confocal laser scanning microscopy. Furthermore, regulation in expression of EMT-related proteins and molecular biomarkers and underlying signal pathway proteins were detected through Western blotting and IHC. Results: The combination of JSD and PD-L1 inhibitor could inhibit migration, invasive ability and EMT of CT-26 cells in a concentration-dependent manner. Meanwhile, JSD combined with PD-L1 inhibitor could also remarkably reverse EMT and metastasis in vivo. In addition, the protein expression of N-cadherin, Slug, Snail, Vimentin was down-regulated along with E-cadherin s up-regulation with the combination of JSD and PD-L1 inhibitor, while that of PI3K/AKT was notably down-regulated. Conclusions: These findings indicated that JSAE and a PD-L1 inhibitor could drastically inhibit the migration and invasion of colorectal cancer by reversing EMT through the PI3K/AKT signaling pathway.


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