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Research in Pharmaceutical Sciences، جلد ۱۹، شماره ۲، صفحات ۲۰۳-۲۱۶
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عنوان انگلیسی Evaluation of in vitro and in vivo anticancer activities of potassium koetjapate: a solubility improved formulation of koetjapic acid against human colon cancer
چکیده انگلیسی مقاله Background and purpose: The previous work on koetjapic acid (KA) isolated from Sandoricum koetjape showed its efficacy towards colorectal cancer however KA has poor water solubility which poses the biggest hindrance to its efficacy. In the present paper, an attempt was made to study the anti-colon cancer efficacy of KA’s potassium salt i.e . potassium koetjapate (KKA) applying in vitro and in vivo methods. Experimental approach: KKA was produced by a semi-synthetic method. A human apoptosis proteome profiler array was applied to determine the protein targets responsible for the stimulation of apoptosis. Three doses of KKA were studied in athymic nude mice models to examine the in vivo anti-tumorigenic ability of KKA. Findings/Results: The results of this study demonstrated that KKA regulates the activities of various proteins. It downregulates the expression of several antiapoptotic proteins and negative regulators of apoptosis including HSP60, HSP90, Bcl-2, and IGF-1 in HCT 116 cells with consequent upregulation of TRAILR-1 and TRAILR-2, p27, CD40, caspase 3, and caspase 8 proteins. Additionally, KKA showed an in vitro antimetastatic effect against HCT 116 cells. These results are feasibly related to the down-regulation of Notch, Wnt, hypoxia, and MAPK/JNK and MAPK/ERK signalling pathways in HCT 116 cells besides the up-regulation of a transcription factor for cell cycle (pRb-E2F) pathways. In addition, KKA revealed potent inhibition of tumor growth. Conclusion and implications: In sum, the findings indicate that KKA can be a promising candidate as a chemotherapeutic agent against colorectal cancer.  
کلیدواژه‌های انگلیسی مقاله Apoptosis,Colon cancer,Hypoxia,MAPK signalling pathways,Potassium koetjapate,TRAILR-1&,2.
نویسندگان مقاله | Fatemeh Jafari
Department of Plant Sciences, Faculty of Biological Sciences, Alzahra University, Tehran, Iran.


| Maryam Keshavarzi
ACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, Australian National University, Australia. EMAN Research Ltd. level 10-14, Wormald Street, Symonston, ACT 2009, Australia and EMAN Biodiscoveries Sdn. Bhd., A1-4, Halal Park, 08000 Sungai Petani, Kedah, Malaysia. Malaysia.


| Amin MalikShah AbdulMajid
EMAN Research Ltd. level 10-14, Wormald Street, Symonston, ACT 2009, Australia and EMAN Biodiscoveries Sdn. Bhd., A1-4, Halal Park, 08000 Sungai Petani, Kedah, Malaysia. Malaysia.


| Fouad Saleih R. Al-Suede
Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur 63100 Punjab, Pakistan.


| Muhammad Asif
CTI Clinical Trial and Consulting Services, Level 21/207 Kent St, Sydney NSW 2000, Australia.


| Mohamed B. Khadeer Ahamed
Independent Researcher, Dallas, TX 75231, Texas, U.S.


| Md Shamsuddin Sultan Khan
Departmrnt of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains, Malaysia.


| Loiy Ahmed Elsir Hassan
Department of Pharmacology, Faculty of Medicine, Quest International University, Malaysia.


| Aman Shah Abdul Majid
Traditional Medicine Clinical Trial Research Centre, Shahed University, Tehran, Iran.


| Mohsen Naseri


نشانی اینترنتی http://rps.mui.ac.ir/index.php/jrps/article/view/2243
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زبان مقاله منتشر شده en
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