Assessment Of The Antitumor Activity Of Leech (Huridinaria Manillensis) Saliva Extract In Prostate Cancer.

e16120 Background: Ancient traditional physicians from many countries used leeching to treat a wide range of diseases for thousands of years. Leech saliva contains a large number of peptides and proteins, which have anti-thrombotic, antimicrobial, antitumor and anti-metastatic activities. Currently, leech therapy has an established role as an important tool in microsurgery, reconstructive surgery and salvage of grafted tissues. Methods: LSE IC50 was determined in-vitro in five prostate cancer cell lines using MTS cell viability assay. In-vivoefficacy of LSE was determined in LNCaP and 22RV-1 in nude mice xenograft models. Castrated tumor bearing mice were divided into four groups of 6-8 each. Mice were subcutaneously injected with either LSE (5 mg/kg) once a week, LSE (5 mg/kg) twice a week, docetaxel (10 mg/kg) or vehicle twice a week for four weeks. PSA, tumor volume, and weight were measured periodically. Results: In-vitro, LSE induced cell death in a panel of five prostate cancer cell lines. In vivo studies showed that LSE once and twice weekly regimens both caused significant decrease in PSA and tumor volume compared to control with no significant difference from docetaxel treated group. Interestingly, once weekly treatment was associated with significant weight gain (due to good dietary intake) at several time points. Immunohistochemical staining (IHC) showed significant decrease in P21and Ki-67 expression in the LSE treated mice compared to the control group in the LNCaP model. Active caspase-3 was increased at once and twice weekly doses in both models confirming the pro-apoptotic properties of LSE.. Transcriptome analysis of tumor samples showed that LSE had significant immunomodulatory, anti-inflammatory, along with significant effects on cell-cell adhesion, induction of glutathione transferase, inhibition of certain growth factors, and modulating several transcription factors. Conclusions: LSE has significant in vitro and in vivo anti-tumor activity with no apparent side effects. This can be attributed, at least partly, to its ability to inhibit cellular proliferation, induce apoptosis and arrest cell cycle through its modulation of immunity, cell-cell adhesion, and inflammation.