Evaluation of in vitro and in vivo anticancer activities of potassium koetjapate: a solubility improved formulation of koetjapic acid against human colon cancer.
| Autor: | Jafari SF; Department of Plant Sciences, Faculty of Biological Sciences, Alzahra University, Tehran, Iran., Keshavarzi M; Department of Plant Sciences, Faculty of Biological Sciences, Alzahra University, Tehran, Iran., AbdulMajid AM; 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., Al-Suede FSR; 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., Asif M; Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur 63100 Punjab, Pakistan., Ahamed MBK; CTI Clinical Trial and Consulting Services, Level 21/207 Kent St, Sydney NSW 2000, Australia., Khan MSS; Independent Researcher, Dallas, TX 75231, Texas, U.S., Hassan LAE; Departmrnt of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains, Malaysia., Majid ASA; Department of Pharmacology, Faculty of Medicine, Quest International University, Malaysia., Naseri M; Traditional Medicine Clinical Trial Research Centre, Shahed University, Tehran, Iran. |
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| Jazyk: | angličtina |
| Zdroj: | Research in pharmaceutical sciences [Res Pharm Sci] 2024 Apr 01; Vol. 19 (2), pp. 203-216. Date of Electronic Publication: 2024 Apr 01 (Print Publication: 2024). |
| DOI: | 10.4103/RPS.RPS_247_22 |
| Abstrakt: | 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. Competing Interests: The authors declared no conflict of interest in this study. (Copyright: © 2024 Research in Pharmaceutical Sciences.) |
| Databáze: | MEDLINE |
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