Abstract
Proteolytic enzymes have shown efficacy in cancer therapy. We present a combination of the two pro-enzymes Trypsinogen and Chymotrypsinogen A with potent in vitro and in vivo anti-tumour efficacy. A synergetic anti-tumour effect for Trypsinogen and Chymotrypsinogen A was determined at a ratio 1:6 (named PRP) using 24 human cancer cell lines. The antiangiogenic effect of PRP was analysed by matrigel-based tube formation and by fibrous capsule formation assays. Furthermore, cell invasion and wound healing assays together with qRT-PCR determination of epithelial-to-mesenchymal transition (EMT) markers were performed on human cancer cells treated with PRP. Additionally, in vivo pharmacokinetic studies were implemented and the PRP’s anti-tumour efficacy was explored against orthotopic pancreatic and ovarian cancer tumours. PRP formulation was proven to inhibit in vitro angiogenesis, tumour growth, cancer cell migration and invasiveness; and to be an effective and well tolerated in vivo anti-tumour treatment. Finally, the clinical efficacy of a suppository formulation containing both pancreatic pro-enzymes in the context of a UK Pharmaceuticals Special Scheme was evaluated in advanced cancer patients. Consequently, PRP could have relevant oncological clinical applications for the treatment of advanced or metastatic pancreatic adenocarcinoma and advanced epithelial ovarian cancer.
Highlights
Cancer is the second most common cause of death in the US
To analyse the anti-metastatic effect of the pro-enzyme treatment we studied the effect of pancreatic pro-enzymes (PRP) in cell invasion, cell migration and in the modulation of epithelial-to-mesenchymal transition (EMT) related genes in pancreatic and ovarian cancer cells
The presented data have been relevant to adopt a new strategy in the formulation of a preparation composed of pancreatic pro-enzymes (PRP) that proved to reduce the main characteristics of cancer spread
Summary
Cancer is the second most common cause of death in the US. According to the American Cancer Society 42% of men and 37% of women are at risk of developing cancer during their life-time. To analyse the anti-metastatic effect of the pro-enzyme treatment we studied the effect of PRP in cell invasion, cell migration and in the modulation of EMT related genes in pancreatic and ovarian cancer cells. We treated mice orthotopically inoculated with A2780 human ovarian cancer cells or with Pan[02] mouse pancreatic tumour cells with PRP.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
