The potential of the metabolites active from Moringa leaves (Moringa oleifera, Lam) on sensitivity of doxorubicin towards breast cancer: in silico studies

FRENGKI FRENGKI, KMS M AMIN ALQADRI, SITI AISYAH, HENNIVANDA HENNIVANDA

Abstract


Breast cancer is one type of cancer with the highest incidence suffered by women. Doxorubicin is a chemotherapy that is often used as the main chemotherapy and combination chemotherapy, but the use of doxorubicin is often complained of side effects that cause auto resistance. Combination with chemopreventives from natural ingredients has become an option to increase therapeutic response and to minimize side effects and resistance to chemotherapy use. This study aims to screen several active compounds of the phenolic-flavonoid group contained in Moringa leaves (Moringa oleifera, Lam) against NFκβ receptors in silico using a molecular docking technique. The material in the form of “Canonical smiles” data is quercetin, quercetin-3 glycoside (Q3G), rutin, kaempferol, myricetin, isorhamnetin, deoxyelephantopin and doxorubicin which were downloaded from www.pubchem.org and converted to 3D structures using MOE software. While the 3D structure of the receptor (1VKX) was downloaded from www.rscb.org. The results of the docking of the active compounds contained in Moringa leaves (Moringa oleifera, Lam) showed a fairly strong affinity by releasing energy when forming a ligand-receptor complex. Quercetin 3-glycoside has the best potential as an NF inhibitor with an affinity of -14.23 kcal/mol. Quercetin 3-glycoside also has a good pharmacokinetic profile with low toxicity. While the phenolic-flavonoid compounds contained in other Moringa leaves are only able to reduce the affinity of doxorubicin for the NF receptor by changing the "site binding" conformation of the receptor. In conclusion, quercetin 3-glycoside deserves to be a drug candidate or a companion to the chemotherapy of doxorubicin.


Keywords


Breast cancer, docking, In silico, Moringa oleifera Lam., NFκβ

References


Griffitsh, E. J. F.; Miller, D.T.; Suzuki, R.D.; Lewontin, W.; and Gelbart, M. 1993. An introduction to genetic Analysis. 5th Ed. W. H. Preeman and Company. New York. 841

Ferlay, J.; Soerjomataram, I.; Ervik, M.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. 2013. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Lyon, France: International Agency for Research on Cancer

Liptak, J.; 2004. Mammary Tumors in cats and dogs. http://www.Acvs.Org/AnimalOwners/HealthConditions/SmallAnimalTopicsMammaryTumorsinCatsandDog/

Kumar, V.; Robbins; Leonard, S. 2010. Neoplasia in: Robbins & Cotran Pathologic Basis of Disease, 8th ed. Philadelphia: Saunders Elsevier. 269-342.

Lacroix, M.; Toillon, R.A.; and Leclercq, G. 2004. Stable ‘portrait’ of breast tumors during progression: data from biology, pathology and genetics. Endocrine-Related Cancer. 11 497–522

Abeloff, M.D.; Wolff, A.C.; Weber, B.L.; Zaks, T.Z.; Sacchini V, and McCormick, B. 2008. Cancer of the Breast. Dalam: Abeloff MD, Armitage JO, Nied erhuber JE, Kastan MB, dan McKenna WG. Editor. Abeloff’s Clinical Oncology. Edisi ke-4 Philadelphia: Churchill Livingstone Elsevier; chap 95

Fauci, A.; Braunwald, E.; Kasper, D.; Hauser, S.; Longo, D.’ Jameson, J.; and Loscalzo, J. 2008. Harrison’s: Principles of Internal Medicine. 17th Edition. USA: The McGraw-Hill Companies. 2275-2299.

Theriault, R. L.; Robert, D.O.; Carlson, R.W.; Allred, C.; Anderson, B.O.; Burstein, H. J.; Edge, S.B.; Farrar, W.B.; Forero, A.; Giordano, S.H.; Goldstein, L.J.; Gradishar, W.J.; Hayes, D.F.; Hudis, C.A.; Isakoff, S.J.; Ljung, B.; M. E.; Mankoff, D.A.; Marcom, P.K.; Mayer, I.A.; Mccormick, B.; Smith, M.L.; Soliman, H.; Somlo, G.; Ward, J.H.; Wolf, A.C.; Zellars, R.; Shead, D.A.; & Kumar, R. 2013. Breast Cancer Version 3. 2013. J Natl Compr Canc Netw. 11(7), 753-761

Speth, P.; Van; Hoesel, Q.; & Haanen, C. 1988. Clinical pharmacokinetics of doxorubicin. Clin. Pharmacokineti. 15 15-31.

Han, C, Y.; Cho, K, B.; Choi, H, S.; Han, H, K.; and Kang, K, W. 2008. Role of FoxO1 actvation in MDR1 ekspression in adriamycin-resistant breast cancer cells. Carsinogenesis. 29(9), 1837-1844

Press, M. F.; Sauter, G.; Buyse, M.; Bernstein, L.; Guzman, R.; Santiago, A.; Villalobos, I. E.; Eiermann, W.; Pienkowski, T.; & Martin, M. 2011. Alteration of topoisomerase II–alpha gene in human breast cancer: Association with responsiveness to anthracycline-based chemotherapy. J. Clin. Oncol. 29 859-867.

Liu, Y.; Du, F.; Chen, W.; Yao, M.; Lv, K.; & Fu, P. 2013. Knockdown of dual specificity phosphatase 4 enhances the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin. Exp. Cell Res. 319 3140-3149.

Weiss, R.B. 1992. The anthracyclines: Will we ever find a better doxorubicin? Semin. Oncol. 19, 670–686.

Bentires-Alj, M; Barbu, V.; Fillet M. 2003. NFkB Transcription Factor Induces Drugs Resistance Through MDR1 Expression in Cancer Cells. Oncogene. 22 90-97

Sui, H.; Fan Z-Z; Li Q. 2012. Signal Transduction Pathway and Transcriptional Mechanism of ABCB1/Pgp-Mediated Multiple Drug Resistance in Human Cancer Cells. J. Int. Med. Res. 40 426-235

Krisnadi, A.D. 2012. Kelor Super Nutrisi. Pusat Informasi dan Pengembangan Tanaman Kelor Indonesia Lembaga Swadaya Masyarakat. Media Peduli Lingkungan (Lsm-Mepeling).

Kumar, A.; Gautam, B.; Dubey, C.; Tripathi, P.K. 2013. A Review: Role of Doxorubicin in Treatment in Cancer. Int. J. Pharm. Sci. Res. 5(10) 4117-4128

Asgharian, P.; Tazekand, AP.; Hosseini, K. et al. 2022. Potential mechanisms of quercetin in cancer prevention: focus on cellular and molecular targets. Cancer Cell Int. 22 257 https://doi.org/10.1186/s12935-022-02677-w

Choi, S.S.; Park, H.R.; Lee, K.A. 2021. A Comparative Study of Rutin and Rutin Glycoside: Antioxidant Activity, Anti-Inflammatory Effect, Effect on Platelet Aggregation and Blood Coagulation. Antioxidants. 10 1696. https://doi.org/10.3390/ antiox10111696

Wang, J.; Fang, X.; Ge, L.; Cao, F.; Zhao, L.; Wang, Z. 2018 Antitumor, antioxidant and anti-inflammatory activities of kaempferol and its corresponding glycosides and the enzymatic preparation of kaempferol. PLoS ONE. 13(5), e0197563. https://doi.org/10.1371/journal. pone.0197563

Makatita, F.A.; Wardhani, R.; Nuraini. 2020. Riset In silico Dalam Pengembangan Sains Di Bidang Pendidikan, Studi Kasus: Analisis Potensi Cendana Sebagai Agen Anti-Aging. Jurnal Abdi. 2 (1) 59

Sing, D, V.; Agarwal, S.; Kesharwani, R, K.; Misra, K. 2013. 3D QSAR and pharmacophore study of curcuminoids and curcumin analogs: interaction with thioredoxin reductase. Interdiscip. Sci. 5(4) 286-95. doi: 10.1007/s12539-013-0177-6.

Frengki, F.; Putra, D.P.; Wahyuni, F.S.; Khambri, D.; Vanda, H. 2019. In silico analysis of wild-type and mutant KRas. Pharmaciana 9(1) 89-98

Kashyap, P.; Kumar, S.; Riar, C.S.; Jindal, N.; Baniwal, P.; Guine, R.P.F.; Correia, P.M.R.; Mehra, R.; Kumar, H. 2022. Recent Advances in Drumstick (Moringa oleifera) Leaves Bioactive Compounds: Composition, Health Benefits, Bioaccessibility, and Dietary Applications. Antioxidants. 11 402

Nouman, W.; Anwar, F.; Gull, T.; Newton, A.; Rosa, E.; Domínguez-Perles, R. 2016. Profiling of polyphenolics, nutrients and antioxidant potential of germplasm’s leaves from seven cultivars of Moringa oleifera Lam. Ind. Crops Prod. 83 166–176

Zhao, B.; Deng, J.; Li, H.; He, Y.; Lan, T.; Wu, D.; Gong, H.; Zhang, Y.; Chen, Z. 2019. Optimization of Phenolic Compound Extraction from Chinese Moringa oleifera Leaves and Antioxidant Activities. J. Food Qual. 5346279

Huang, C.C.; Lo, C.P.; Chiu, C.Y.; Shyur, L.F. 2010. Deoxyelephantopin a novel multifunctional agent suppresses mammary tumor growth and lung metastasis and doubles survival time in mice. Br. J. Pharmacol. 159(19) 856-871.


Full Text: PDF

DOI: 10.24815/jn.v23i2.31142

Refbacks

  • There are currently no refbacks.