In vivo assessment of the therapeutic effects of lyophilized leech saliva extract from (Huridinaria manillensis) on LNCaP tumor xenograft model in nude mice

Background: Ancient traditional physicians from many countries used leeching to treat a wide range of diseases for thousands of years. A large number of peptides and proteins have been identified and characterized in leech saliva extract (LSE), including anti­ thrombotic agents, cancer metastasis...

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Main Authors: Ammar, Amr, Hessein, Mohamed, Guns, Emma, Chin, Mei, Helal Uddin, A.B.M., Abdualkader, Abdulrahman, Alaama, Mohammed, Merzouk, Ahmed, Ghawi, Abbas, Kucuk, Omer
Format: Article
Language:English
Published: American Society of Clinical Oncology 2015
Subjects:
Online Access:http://irep.iium.edu.my/49434/
http://irep.iium.edu.my/49434/1/In%C2%A0vivo%C2%A0assessment%C2%A0of%C2%A0the%C2%A0therapeutic%C2%A0effects%C2%A0of%C2%A0lyophilized%C2%A0leech.pdf
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author Ammar, Amr
Hessein, Mohamed
Guns, Emma
Chin, Mei
Helal Uddin, A.B.M.
Abdualkader, Abdulrahman
Alaama, Mohammed
Merzouk, Ahmed
Ghawi, Abbas
Kucuk, Omer
author_facet Ammar, Amr
Hessein, Mohamed
Guns, Emma
Chin, Mei
Helal Uddin, A.B.M.
Abdualkader, Abdulrahman
Alaama, Mohammed
Merzouk, Ahmed
Ghawi, Abbas
Kucuk, Omer
author_sort Ammar, Amr
building IIUM Repository
collection Online Access
description Background: Ancient traditional physicians from many countries used leeching to treat a wide range of diseases for thousands of years. A large number of peptides and proteins have been identified and characterized in leech saliva extract (LSE), including anti­ thrombotic agents, cancer metastasis inhibitors and anti­microbials Currently, leech therapy is established as an important tool in microsurgery and reconstructive operations having demonstrated superior clinical outcomes for the optimal salvage of grafted tissues. Methods: In the current study, we have determined the in vivo efficacy of LSE from (Huridinaria manillensis) on castration resistant LNCaP xenograft mouse model. Mice were divided into three groups of six, mice were subcutaneously injected with either LSE (5 mg/kg), docetaxel (10 mg/kg), or vehicle once a week. PSA and tumor volume were measured weekly. After four weeks of treatment, mice were euthanized, tumors and organs were collected for transcriptome and immunohistochemical (IHC) analysis. Results: There was a significant decrease in the tumor volume and PSA with either docetaxel (10mg/kg) or LSE (5 mg/kg) treated groups compared to the control. While there was no significant difference between the anti­tumor activity of docetaxel (10mg/kg) and LSE (5 mg/kg). IHC showed significant increase in caspase­3 and significant decrease in Ki­67 and PCNA expression in the LSE treated mice compared to the control group. Interestingly, transcriptome analysis of tumor samples showed that LSE modulated cytokine production, monocyte adhesion, steroidogenesis, and P38 MAPK signaling pathways. Conclusions: LSE has significant anti­tumor activity in LNCaP tumor xenograft models with no apparent side effects. This can be attributed, at least partly, to its inhibition of cellular proliferation, induction of apoptosis, modulation of immunity and steroidogenesis.
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spelling iium-494342022-11-07T03:22:11Z http://irep.iium.edu.my/49434/ In vivo assessment of the therapeutic effects of lyophilized leech saliva extract from (Huridinaria manillensis) on LNCaP tumor xenograft model in nude mice Ammar, Amr Hessein, Mohamed Guns, Emma Chin, Mei Helal Uddin, A.B.M. Abdualkader, Abdulrahman Alaama, Mohammed Merzouk, Ahmed Ghawi, Abbas Kucuk, Omer RM Therapeutics. Pharmacology RS Pharmacy and materia medica Background: Ancient traditional physicians from many countries used leeching to treat a wide range of diseases for thousands of years. A large number of peptides and proteins have been identified and characterized in leech saliva extract (LSE), including anti­ thrombotic agents, cancer metastasis inhibitors and anti­microbials Currently, leech therapy is established as an important tool in microsurgery and reconstructive operations having demonstrated superior clinical outcomes for the optimal salvage of grafted tissues. Methods: In the current study, we have determined the in vivo efficacy of LSE from (Huridinaria manillensis) on castration resistant LNCaP xenograft mouse model. Mice were divided into three groups of six, mice were subcutaneously injected with either LSE (5 mg/kg), docetaxel (10 mg/kg), or vehicle once a week. PSA and tumor volume were measured weekly. After four weeks of treatment, mice were euthanized, tumors and organs were collected for transcriptome and immunohistochemical (IHC) analysis. Results: There was a significant decrease in the tumor volume and PSA with either docetaxel (10mg/kg) or LSE (5 mg/kg) treated groups compared to the control. While there was no significant difference between the anti­tumor activity of docetaxel (10mg/kg) and LSE (5 mg/kg). IHC showed significant increase in caspase­3 and significant decrease in Ki­67 and PCNA expression in the LSE treated mice compared to the control group. Interestingly, transcriptome analysis of tumor samples showed that LSE modulated cytokine production, monocyte adhesion, steroidogenesis, and P38 MAPK signaling pathways. Conclusions: LSE has significant anti­tumor activity in LNCaP tumor xenograft models with no apparent side effects. This can be attributed, at least partly, to its inhibition of cellular proliferation, induction of apoptosis, modulation of immunity and steroidogenesis. American Society of Clinical Oncology 2015-03 Article PeerReviewed application/pdf en http://irep.iium.edu.my/49434/1/In%C2%A0vivo%C2%A0assessment%C2%A0of%C2%A0the%C2%A0therapeutic%C2%A0effects%C2%A0of%C2%A0lyophilized%C2%A0leech.pdf Ammar, Amr and Hessein, Mohamed and Guns, Emma and Chin, Mei and Helal Uddin, A.B.M. and Abdualkader, Abdulrahman and Alaama, Mohammed and Merzouk, Ahmed and Ghawi, Abbas and Kucuk, Omer (2015) In vivo assessment of the therapeutic effects of lyophilized leech saliva extract from (Huridinaria manillensis) on LNCaP tumor xenograft model in nude mice. Journal of Clinical Oncology, 33 (7 (Supp.)). p. 271. ISSN 0732-183X E-ISSN 1527-7755 http://meeting.ascopubs.org/cgi/content/abstract/33/7_suppl/271?sid=2ea1a1d4-9eeb-4f02-8270-cfffe2db25a5
spellingShingle RM Therapeutics. Pharmacology
RS Pharmacy and materia medica
Ammar, Amr
Hessein, Mohamed
Guns, Emma
Chin, Mei
Helal Uddin, A.B.M.
Abdualkader, Abdulrahman
Alaama, Mohammed
Merzouk, Ahmed
Ghawi, Abbas
Kucuk, Omer
In vivo assessment of the therapeutic effects of lyophilized leech saliva extract from (Huridinaria manillensis) on LNCaP tumor xenograft model in nude mice
title In vivo assessment of the therapeutic effects of lyophilized leech saliva extract from (Huridinaria manillensis) on LNCaP tumor xenograft model in nude mice
title_full In vivo assessment of the therapeutic effects of lyophilized leech saliva extract from (Huridinaria manillensis) on LNCaP tumor xenograft model in nude mice
title_fullStr In vivo assessment of the therapeutic effects of lyophilized leech saliva extract from (Huridinaria manillensis) on LNCaP tumor xenograft model in nude mice
title_full_unstemmed In vivo assessment of the therapeutic effects of lyophilized leech saliva extract from (Huridinaria manillensis) on LNCaP tumor xenograft model in nude mice
title_short In vivo assessment of the therapeutic effects of lyophilized leech saliva extract from (Huridinaria manillensis) on LNCaP tumor xenograft model in nude mice
title_sort in vivo assessment of the therapeutic effects of lyophilized leech saliva extract from (huridinaria manillensis) on lncap tumor xenograft model in nude mice
topic RM Therapeutics. Pharmacology
RS Pharmacy and materia medica
url http://irep.iium.edu.my/49434/
http://irep.iium.edu.my/49434/
http://irep.iium.edu.my/49434/1/In%C2%A0vivo%C2%A0assessment%C2%A0of%C2%A0the%C2%A0therapeutic%C2%A0effects%C2%A0of%C2%A0lyophilized%C2%A0leech.pdf