Sarah Ika Nainggolan, Rajuddin Rajuddin, Hasanuddin Hasanuddin, Reno Keumalazia, Muhammad Hambal, Frengki Frengki
Sarah Ika Nainggolan1,2, Rajuddin Rajuddin2*, Hasanuddin Hasanuddin3, Reno Keumalazia2, Muhammad Hambal4, Frengki Frengki4
1Doctoral Education Program in Mathematics and Clinical Applications, Faculty of Mathematics and Natural Sciences, Syiah Kuala University.
2Department of Obstetrics and Gynecology, Division of Gynecological Endocrinology, Faculty of Medicine, Syiah Kuala University, Banda Aceh, Indonesia.
3Department of Obstetrics and Gynecology, Division of Gynecological Oncology, Faculty of Medicine, Syiah Kuala University, Banda Aceh, Indonesia.
4Faculty of Veterinary Medicine, Syiah Kuala University, Banda Aceh, Indonesia.
Volume - 16,
Issue - 2,
Year - 2023
Curcuminoids are widely known to have biological activities such as antioxidant, anti-inflammatory, antiarthritis and anticancer. Even the use of curcumin has reached the first stage of clinical trials in overcoming a number of cancers. Interestingly, a number of curcumin metabolites also have anticancer effects that are equivalent to or even better than curcumin through a series of preclinical tests, but the description of their molecular interactions is still very limited so that in silico evidence is needed. QSAR and Molecular Docking were used as test methods using MOE 2008 software version 10. The research material was a 3D structure of curcumin derivative for QSAR analysis and curcumin metabolites for molecular docking analysis. Receptors downloaded from www.rscb.org include the 3D structure of MAPK, Akt, MDM2, NFkB, Cox-2, and VEGF, while the 3D structure of “human tubulin -1” was obtained from modeling. The QSAR results show that the anticancer activity of curcumin metabolites is stronger than curcumin except for dihydrocurcumin. The docking results also show that curcumin metabolites have the same affinity, even stronger than curcumin and control receptors with docking scores between 10-16kcal/mol. Curcumin and its metabolites were also able to increase the affinity of paclitaxel to the "human tubulin -1" receptor model as the target of paclitaxel's action which was characterized by an increase in the post-combination paclitaxel decking score. This study shows that curcumin is very suitable to be used as an anticancer because not only curcumin, but its metabolites also show better anticancer abilities.
Cite this article:
Sarah Ika Nainggolan, Rajuddin Rajuddin, Hasanuddin Hasanuddin, Reno Keumalazia, Muhammad Hambal, Frengki Frengki. In silico Analysis of Anticancer Curcumin and its Metabolites in increasing the effectiveness of Paclitaxel. Research Journal of Pharmacy and Technology 2023; 16(2):885-2. doi: 10.52711/0974-360X.2023.00150
Sarah Ika Nainggolan, Rajuddin Rajuddin, Hasanuddin Hasanuddin, Reno Keumalazia, Muhammad Hambal, Frengki Frengki. In silico Analysis of Anticancer Curcumin and its Metabolites in increasing the effectiveness of Paclitaxel. Research Journal of Pharmacy and Technology 2023; 16(2):885-2. doi: 10.52711/0974-360X.2023.00150 Available on: https://rjptonline.org/AbstractView.aspx?PID=2023-16-2-69
1. Amalraj A, Anitha P, Sreerag G. Biological activities of curcuminoids, other biomolecules from turmeric and their derivatives. A review article. J Tradit Complement Med. 2016 Jun 15; 7(2):205-233. https://doi.org/10.1016/j.jtcme.2016.05.005
2. Park W, A.R.M. Ruhul A, Zhuo GC, Dong MS. New Perspectives of Curcumin in Cancer Prevention. Cancer Prev Res (Phila). 2013 May; 6(5):387-400. doi: 10.1158/1940-6207.CAPR-12-0410. Epub 2013 Mar 6
3. Meiyanto E, Rosita M, Muhammad D. PGV-1 decreases angiogenic factor (VEGF and COX-2) expression on T47D cell induced by estrogen. Indonesian Journal of Pharmacy. 2006; 17(1): 1 – 6. http://dx.doi.org/10.14499/indonesianjpharm0iss0pp1-6
4. Binion DG, MF Otterson, P Rafiee. Curcumin inhibits VEGF-mediated angiogenesis in human intestinal microvascular endothelial cells through COX-2 and MAPK inhibition. Gut. 2008; 57:1509–1517. http://dx.doi.org/10.1136/gut.2008.152496
5. Kim B, Changkyu L, Eun SL, Beom SS, Yu SY. Paclitaxel and curcumin co-bound albumin nanoparticles having antitumor potential to pancreatic cancer. Asian Journal of Pharmaceutical Sciences. 2016; 11: 88-714. http://dx.doi.org/10.1016/j.ajps.2016.05.005
6. Saghatelyana T, Armen T, Naira J, Anna T , Hasmik P, Araxia H, Lidia H, Mikael A, Jurgen A, Andre-Robert R, Areg H, Alexander P. Efficacy and safety of curcumin in combination with paclitaxel in patients with advanced, metastatic breast cancer: A comparative, randomized, double-blind, placebo-controlled clinical trial. Phytomedicine. 2020; 70. 153218. https://doi.org/10.1016/j.phymed.2020.153218
7. Pandey A, Maya C, Shruti M, Pramod K, Pallavi S, Rupesh C. Reductive metabolites of curcumin and their therapeutic effects. Review Arcticle. Heliyon 6 (2020) e05469. https://doi.org/10.1016/j.heliyon.2020.e05469
8. Yu Q, Yayun L, Yufei W, Young C. Dihydrocurcumin ameliorates the lipid accumulation, oxidative stress and insulin resistance in oleic acid-induced L02 and HepG2 cells. Biomed Pharmacother. 2021; 103:1327–1336. https://doi.org/10.1016/j.biopha.2018.04.143
9. Liu W, Zhenbiao Z, Guosheng L, Dandon L, Hanbin C, Hongmei Y, Jiali L, Yuhong L, Jianhui X, Ziren S, Hongying C. Tetrahydrocurcumin is more effective than curcumin in inducing the apoptosis of H22 cells via regulation of a mitochondrial apoptosis pathway in ascites tumor-bearing mice. Food & function. 2017; 8(9): 3120–3129. https://doi.org/10.1039/C7FO00484B
10. Mohankumar K, Sankar P, Subhashree S, Vivek KS, Larance R, Akhil CB, Chelakkan SB, Mohane SC, Rukkumani R. Mechanism of apoptotic induction in human breast cancer cell, MCF-7, by an analog of curcumin in comparison with curcumin - An in vitro and in silico approach. Chemico-Biological Interaction. 2014; 210(5): 51-63. https://doi.org/10.1016/j.cbi.2013.12.006
11. Zhang ZB, Dan-Dan L, Jian-Hui X, Yan-Fang X, Zheng-Quan L, Yu-Hong L, Wei-Hai L, Jian-Nan C, Xiao-Ping L, Zhi-Xiu L, Zi-Ren S. Curcumin’s metabolites, tetrahydrocurcumin and octahydrocurcumin, possess superior antiinflammatory effects in vivo through suppression of TAK1-NF-κb pathway. Front. Pharmacol. 2018; 9 (OCT):1–12. https://doi.org/10.3389/fphar.2018.01181
12. Zhang ZB, Dn-Dan L, Jianhui X, Guesheng L, Jiangtau Z, Weihai L, Huilin L, Tiegang Y, Ziren S, Jianping C. Octahydrocurcumin, a final hydrogenated metabolite of curcumin, possesses superior anti-tumor activity through induction of cellular apoptosis. Food & function. 2018; 9 (4): 2005–2014. https://doi.org/10.1039/C7FO02048A
13. Meng X, Lianhua C, Fucheng S, Mingyuan L, Junjie J, Hongzong S, Yunbo D, Honglin Z. 3D-QSAR and Molecular Docking Studies on Design Anti Prostate Cancer Curcumin Analogues. Current Computer-Aided Drug Design 2000; 16(3): 245-256 doi: 10.2174/1573409914666181029123746
14. Tropsha, A. Best Practices for QSAR Model Development, Validation, and Exploitation. Molecular Informatics. 2010; 29(6-7), 476-488. https://doi.org/10.1002/minf.201000061
15. Sinha R, Ambarish V, Shankaracharya. A molecular docking study of anticancer drug paclitaxel and its analogues. Indian Journal of Biochemisty & Biophysics. 2011; 48(2): 101-105. doi: 10.1080/03772063.2021.1878063
16. Huang CC, Chiuping L, Chihyang C and Liefen S. Deoxyelephantopin a novel multifunctional agent, suppresses mammary tumor growth and lung metastasis and double survival time in mice. British Journal of Pharmacology. 2010; 159(19): 856-871. https://doi.org/10.1111/j.1476-5381.2009.00581.x
17. Frengki, Dedi PR, Fatma SR, Daan K, Henni V. Nfκβ Inhibition Mechanism of Deoxyelephantopin and Isodeoxyelephantopin with QSAR and Molecular Docking. IJPSR. 2019; Vol. 10(7): 3228-3233. http://dx.doi.org/10.13040/IJPSR.0975-8232.10(7).3228-33
18. Pantoro BI, Nancy MR, Siti K, Anna SV, Yuniati S. In Silico Analysis of Turmeric (Curcuma Longa) as a Murine Double Minute 2 Protein Inhibitor for Treatment of Glioblastoma Multiforme. Oceana Biomedicina Journal. 2020; 3(2): 145-158
19. Yuniarti N, Perdana AN, Aditya A, Sardjiman S, Zuliies I, Enade PI. In vitro and In Silico Studies on Curcumin and Its Analogues as Dual Inhibitors for cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). ITB J. Sci. 2012; 44(1): 51-66. https://doi.org/10.5614/itbj.sci.2012.44.1.5
20. Kalyaanamoorthy S, Yie-Ping PC. Structure-based Drug Design to Augment Hit Discovery. Drug Discovery Today. 2011; 16(17/18): 831-839. https://doi.org/10.1016/j.drudis.2011.07.006
21. Frengki, Dedi PR, Fatma SR, Daan K, Henni V. In silico analysis of wild-type and mutant KRAS. Pharmaciana. 2019; 9(1): 89-98. https://doi.org/10.12928/pharmaciana.v%vi%i.11384