THE POTENTIAL OF ACTIVE COMPOUNDS Polyscias Scutellaria AS INHIBITORS IN CERVICAL CANCER WITH VIRTUAL SCREENING APPROACH

Muhammad Rizki Kurniawan, Aji Humaedi

Abstract


Cervical cancer is a gynecologic disease that has a high enough malignancy that affects women. In cervical cancer, it is known that the overexpression of Bcl-2 protein is 14.3% in non-invasive cervical carcinoma and 65.2% in invasive cervical carcinoma. The Bcl-2 protein is an important regulator of growth and differentiation pathways. Bcl-2 has anti-apoptotic activity but permeabilization occurs through the mitochondrial pathway, triggering the release of cytochrome c, which then interacts with Apaf-1 for caspase-9 activation and apoptosis occurs. This study aims to determine the mechanism of inhibition of overexpression of Bcl-2 protein by bioactive compounds from the Polyscias scutellaria plant with a virtual screening approach through in silico studies. The in silico study was carried out with the stages of tracking molecular targets, preparation, optimization, simulation and analysis of docking results. The results of the docking analysis showed that the bioactive compounds of the mangkokan plant provided inhibitory activity with gibbs energy values of -6.07, -5.18, -5.43 and -6.02, respectively. Thus the bioactive compounds from the mangkokan plant have potential as Bcl-2 inhibitors in cervical cancer.


Keywords


Cervical Cancer; Polyscias scutellaria; Virtual Screening; Docking Simulation

Full Text:

PDF

References


Bai, X., Ma, Y., & Zhang, G. (2015). Butein suppresses cervical cancer growth through the PI3K/AKT/mTOR pathway. Oncology reports, 33(6), 3085-3092.

Chen, G., Zhou, D., Li, X. Z., Jiang, Z., Tan, C., Wei, X. Y., ... & Li, N. (2017). A natural chalcone induces apoptosis in lung cancer cells: 3D-QSAR, docking and an in vivo/vitro assay. Scientific reports, 7(1), 1-10.

Campbell, K. J., & Tait, S. W. (2018). Targeting BCL-2 regulated apoptosis in cancer. Open biology, 8(5), 180002.

Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., … Bray, F. (2015). Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International Journal of Cancer. Journal International Du Cancer, 136(5),E359–86. doi:10.1002/ijc.29210.

Fang, J., Liu, C., Wang, Q., Lin, P., & Cheng, F. (2018). In silico polypharmacology of natural products. Briefings in bioinformatics, 19(6), 1153-1171.

Giarnieri, E., Mancini, R., Pisani, T., & Alderisio, M. (2000). Msh2, Mlh1, Fhit, p53, Bcl-2, and Bax expression in invasive and in situ squamous cell carcinoma of the uterine cervix. Clinical cancer research, 6(9), 3600-3606.

Humaedi, A., Arsianti, A., & Radji, M. (2017). In Silico Molecular Docking Study of Gallic Acid and its Derivatives as Inhibitor BRAF Colon Cancer. International Journal of ChemTech Research, 10(1), 310-315.

Hirata, H., Lopes, G. S., Jurkiewicz, A., Garcez-do-Carmo, L., & Smaili, S. S. (2012). Bcl-2 modulates endoplasmic reticulum and mitochondrial calcium stores in PC12 cells. Neurochemical research, 37(2), 238-243.

Kurniawan R.M., Humaedi A., Ritonga F.A. (2020). Direct Investigation of Synthesis of Gold Nanoparticles Using Polyscias scutellaria Leaf Extract In the Hexane-Water System Using the Centrifugal Liquid Membrane-Sphectrophotometry Method. Journal of Scientific and Applied Chemistry, 7, 255-260.https://doi.0rg/10.14710/jksa.23.7.255-260.

Madden, K., Flowers, L., Salani, R., Horowitz, I., Logan, S., Kowalski, K., ... & Mohammed, S. I. (2009). Proteomics-based approach to elucidate the mechanism of antitumor effect of curcumin in cervical cancer. Prostaglandins, leukotrienes and essential fatty acids, 80(1), 9-18.

Newman, D. J., & Giddings, L. A. (2014). Natural products as leads to antitumor drugs. Phytochemistry Reviews, 13(1), 123-137.

Riset Kesehatan Dasar. (2018). Jakarta: Badan Penelitian dan Pengembangan Kesehatan, Kementerian Kesehatan, Republik Indonesia

Sathishkumar, N., Sathiyamoorthy, S., Ramya, M., Yang, D. U., Lee, H. N., & Yang, D. C. (2012). Molecular docking studies of anti-apoptotic BCL-2, BCL-XL, and MCL-1 proteins with ginsenosides from Panax ginseng. Journal of enzyme inhibition and medicinal chemistry, 27(5), 685-692.

Thomas, S., Quinn, B. A., Das, S. K., Dash, R., Emdad, L., Dasgupta, S., … Fisher, P. B. (2013). Targeting the Bcl-2 family for cancer therapy. Expert Opinion on Therapeutic Targets, 17(1), 61–75.

Tice, C. M. (2001). Selecting the right compounds for screening: does Lipinski's Rule of 5 for pharmaceuticals apply to agrochemicals?. Pest Management Science: formerly Pesticide Science, 57(1), 3-16.

World Health Organization. (2020). Indonesian Cancer Country Profiles. diunduh pada tanggal 11 Agustus 2020 dari http://www.who.int/cancer/country-profiles/idn_en.pdf?ua=1.

Wang, K., Zhu, X., Zhang, K., Zhu, L., & Zhou, F. (2014). Investigation of Gallic Acid Induced Anticancer Effect in Human Breast Carcinoma MCF-7 Cells. Journal of Biochemical Molecular Toxicology, 28(9), 387–393. http://doi.org/10.1002/jbt.21575.

Xu, L., Xie, Q., Qi, L., Wang, C., Xu, N., Liu, W., ... & Xu, Y. (2018). Bcl-2 overexpression reduces cisplatin cytotoxicity by decreasing ER-mitochondrial Ca2+ signaling in SKOV3 cells. Oncology reports, 39(3), 985-992.




DOI: http://dx.doi.org/10.24817/jkk.v43i1.6836

Refbacks

  • There are currently no refbacks.


Copyright (c) 2021 Muhammad Rizki Kurniawan

Jurnal Kimia dan Kemasan is indexed by:

Creative Commons License

This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.