Chinese medicine bark extract Nexrutine® may reduce fibrosis in pancreatic cancer

Version française

Nexrutine® is an extract from the bark of the Amur cork tree Phellodendron amurense (figure 1), a source used in traditional Chinese medicine. In pancreatic cancer cell lines Nexrutine® induced apoptosis and reduced the activity of STAT3 and NF-κB [1]. This is important as STAT3 and NF-κB promote epithelial mesenchymal transition (EMT) in pancreatic cancer, a contributor to fibrosis which reduces the penetrance of drugs.

 

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Figure 1: Amur cork tree Phellodendron amurense. Credit: Romana Klee. No changes were made. Creative Commons Attribution-ShareAlike 2.0 Generic (CC BY-SA 2.0).

 

STATs are transcription factors which are normally present in the cytoplasm and activated by inflammatory signalling associated with EMT which leads to their nuclear import [2]. STAT3 expression is maintained and constitutive activation has been reported in at least 30% of pancreatic cancers [3]. Likewise transcription factor NF-κB is constitutively active in pancreatic ductal adenocarcinoma (PDAC) and promotes EMT [4]. The EMT enhances the drug resistance of cancer cells. It could therefore be predicted that Nexrutine® would enhance the effectiveness of chemotherapeutics.

 

Indeed in PDAC cell lines it was found that Nexrutine® enhanced sensitivity to the standard chemotherapeutic gemcitabine [5]. The potential anti-fibrotic mechanism of action of Nexrutine® should be investigated further as the stromal environment of pancreatic cancer is also a major obstacle facing the new class of immunotherapeutics in addition to traditional drugs.

 

Refs

 

  1. Gong, J., J. Xie, R. Bedolla, P. Rivas, D. Chakravarthy, J. W. Freeman, R. Reddick, et al. ‘Combined Targeting of STAT3/NF- B/COX-2/EP4 for Effective Management of Pancreatic Cancer’. Clinical Cancer Research 20, no. 5 (1 March 2014): 1259–73. doi:10.1158/1078-0432.CCR-13-1664.
  2. Kaplan, Mark H. ‘STAT Signaling in Inflammation’. JAK-STAT 2, no. 1 (January 2013): e24198. doi:10.4161/jkst.24198.
  3. Corcoran, R. B., G. Contino, V. Deshpande, A. Tzatsos, C. Conrad, C. H. Benes, D. E. Levy, J. Settleman, J. A. Engelman, and N. Bardeesy. ‘STAT3 Plays a Critical Role in KRAS-Induced Pancreatic Tumorigenesis’. Cancer Research 71, no. 14 (15 July 2011): 5020–29. doi:10.1158/0008-5472.CAN-11-0908.
  4. Maier, Harald J., Uta Schmidt-Strassburger, Margit A. Huber, Eva M. Wiedemann, Hartmut Beug, and Thomas Wirth. ‘NF-kappaB Promotes Epithelial-Mesenchymal Transition, Migration and Invasion of Pancreatic Carcinoma Cells’. Cancer Letters 295, no. 2 (28 September 2010): 214–28. doi:10.1016/j.canlet.2010.03.003.
  5. Gong, Jingjing, Amanda R. Muñoz, Subramanya Pingali, Florastina Payton-Stewart, Daniel E. Chan, James W. Freeman, Rita Ghosh, and Addanki P. Kumar. ‘Downregulation of STAT3/NF-κB Potentiates Gemcitabine Activity in Pancreatic Cancer Cells’. Molecular Carcinogenesis, 21 May 2016. doi:10.1002/mc.22503.
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