Bioinformatic Test and Pharmacokinetic Profile Prediction of Gnetin-C Compound in Melinjo (Gnetum gnemon L.) Seeds Toward Colorectal Cancer

Ivana Kinanti Kenyori; Rifki Febriansah

doi:10.14499/indonesianjcanchemoprev15iss1pp18-25

Bioinformatic Test and Pharmacokinetic Profile Prediction of Gnetin-C Compound in Melinjo (Gnetum gnemon L.) Seeds Toward Colorectal Cancer

Ivana Kinanti Kenyori, Rifki Febriansah

Abstract

Cancer is one of the unresolved health problems in the world, including Indonesia. One of the most common types of cancer is colorectal cancer. Melinjo (Gnetum gnemon L.) is one of Indonesian local commodities which has many benefits including its potential to be developed as an anticancer agent. Through bioinformatics and molecular docking technology, the aim of this study was to investigate the functions of gnetin-C from melinjo against colorectal cancer. PkCSM database were used to search the ADMET (absorption, distribution, metabolism, elimination and toxicity) properties and stitch-string database were used to identify common genes related to colon cancer. During identification of colon cancer related genes, STAT3 protein showed the highest degree score. Furthermore, molecular docking was carried out to find out the interaction between the STAT3 protein and gnetin c compound found in melinjo seeds. From the docking stage, the pose with the best affinity energy was obtained with a docking score of 1,966 kcal/mol. this shows that the compound gnetin c has the potential to be used as a new anticancer agent from natural ingredients.

Keywords: Melinjo, Gnetum gnemon, colon cancer, bioinformatics, molecular docking.

Full Text:

PDF

References

Altun, I., and Sonkaya, A., 2018, The Most Common Side Effects Experienced by Patients Were Receiving First Cycle of Chemotherapy, Iran Journal Public Health, 47(8), 1218-1219. Link

Amjad, M.T., Chidharla, A., and Kasi, A., 2023, In Cancer Chemotherapy. s.l.: StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK564367/. Link

Arwansyah, Ambarsari, L., and Sumaryada, T.I., 2014, Simulasi Docking Senyawa Kurkumin dan Analognya Sebagai Inhibitor Reseptor Androgen Pada Kanker Prostat, Current Biochemistry, 1(1), 11-19. Link

Boland, C.R., and Goel, A., 2010, Microsatellite instability in colorectal cancer, Gastroenterology, 138(6), 2073-2087. CrossRef

Dewi, C., Utami, R., and Riyadi, N.H., 2012, aktivitas antioksidan dan antimikroba ekstrak melinjo (Gnetum gnemon L.), Jurnal Teknologi Hasil Pertanian, 5(2), 74-81. CrossRef

Gan, Y., Li, X., Han, S., Zhou, L., and Li, W., 2023, Targeting Mcl-1 Degradation by Bergenin Inhibits Tumorigenesis of Colorectal Cancer Cells, Pharmaceuticals, 16(2), 241. CrossRef

Gargalionis, A.N., Papavassiliou, K.A., and Papavassiliou, A.G., 2021, Targeting STAT3 Signaling Pathway in Colorectal Cancer, Biomedicines, 9(8), 1016. CrossRef

Hanif, A.U, Lukis, P.A., and Fadlan, A., 2020, Pengaruh Minimisasi Energi MMFF94 dengan MarvinSketch dan Open Babel PyRx pada Penambatan Molekular Turunan Oksindola Tersubstitusi, Alchemy Journal of Chemistry, 8(2), 33-40. CrossRef

Kardela, W., Fauziah, F., and Mayesri, S., 2018, Biji Melinjo (Gnetum gnemon L.): Aktivitas Sebagai Antidiare, Jurnal Farmasi Higea, 10(1), 49-57. CrossRef

Kenyori, I.K., Alamsyah, M.S., and Nurjanah, C.I.A., 2022, Studi In Silico Senyawa Bioaktif Kuersetin kulit Jeruk Nipis (Citrus aurantifolia) Sebagai Agen Antikanker Payudara, Berkala Ilmiah Mahasiswa Farmasi, 9(1), 1-10. Link

Krihariyani, D., Sasongkowati, R., and Haryanto, E., 2020, Studi In Silico Sifat Farmakokinetik, Toksisitas, dan Aktivitas Imunomodulator Brazilein Kayu Secang Terhadap Enzim 3-Chymotrypsin-Like Cysteine Protease Coronavirus, Journal of Indonesian Medical Laboratory and Science, 1(1), 76-90. CrossRef

Kuhn, M., von Mering, C., Campillos, M., Jensen, L.J., and Bork, P., 2008, STITCH : interaction networks of chemicals and proteins, Nucleic Acids Research, 36(suppl 1), D684-D688. CrossRef

Kusmiati, A., Haryani, T.S., and Triastinurmiatiningsih, 2019, Aktivitas Ekstrak Etanol 96% Kulit Biji Melinjo (Gnetum gnemon) Sebagai Antibakteri Salmonella enteritidis, Ekologia, 19(1), 27-33. CrossRef

Lelita, R., Gunawan, R., and Astuti, W., 2017, Studi Docking Molekular Senyawa Kuersetin, Kalkon dan Turunannya Sebagai Inhibitor Sel Kanker Payudara MCF-7 (MICHIGAN CANCER FOUNDATION-7), Jurnal Atomik, 2(2), 190-196. Link

Lins, L., and Brasseur, 1995, The hydrophobic effect in protein folding, The FASEB Journal, 9(7), 535-540. CrossRef

Marmol, I., Sanchez-de-Diego, C., Dieste, A.P., Cerrada, E., and Yoldi, M.J.R., 2017, Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer, International Journal of Molecular Sciences, 18(1), 197. CrossRef

Meng, X-Y., Zhang, H-X., Mezei, M., and Cui, M., 2011, Molecular Docking: A powerful approach for structure-based drug discovery, Current Computer-Aided Drug Design, 7(2), 146-157. CrossRef

Mylanda, V., Ramadhan, N.E., and Viviani, R.N., 2021, Studi Penambatan Molekuler Senyawa Bioaktif Biji Habbatussauda (Nigella sativa) Terhadap ERα Sebagai Alternatif Pengobatan Kanker Payudara Dalam Upaya Pemberian Data Ilmiah, Berkala Ilmiah Mahasiswa Farmasi, 8(1), 13-25. CrossRef

Narayanan, N.K., Kunimasa, K., Yamori, Y., Mori, M., Mori, H., Nakamura, K., Miller, G., et al., 2015, Antitumor activity of melinjo (Gnetum gnemon L.) seed extract in human and murine tumor models in vitro and in colon-26 tumor-bearing mouse model in vivo, Cancer Medicine, 4(11), 1767-1780. CrossRef

Pino, M.S., and Chung, D.C., 2010, The chromosomal instability pathway in colon cancer, Gastroenterology, 138(6), 2059-2072. CrossRef

Prajnaparamita, K., and Susanti, S., 2021, Karakter Morfologis dan Perkembangan Anatomis Biji Melinjo (Gnetum Gnemon L.), Jurnal Biogenesis, 17(2), 49-60. CrossRef

Rastini, M.B.O., Giantari, N.K.M., Andyani, K.D., and Laksmiani, N.P.L., 2019, Molecular Docking Aktivitas Antikanker dari Kuersetin Terhadap Kanker Payudara Secara In Silico, Jurnal kimia (Journal of Chemistry), 13(02), 180-184. CrossRef

Ryuk, J.P., Choi, G-S., Park, J.S., Kim, H.J., Park, S.Y., Yoon, G.S., et al., 2014, Predictive factors and the prognosis of recurrence of colorectal cancer within 2 years after curative resection, Annals of surgical treatment and research, 86(3), 143-51. CrossRef

Sari, I.W, Junaidin, and Pratiwi, D., 2020, Studi Molecular Docking Senyawa Flavonoid Herba Kumis Kucing (Orthosiphon stamineus B.) Pada Reseptor α-Glukosidase Sebagai Antidiabetes Tipe 2, Jurnal Farmagazine, 7(2), 54-60. CrossRef

Sari, M.I., Wahid, I., and Suchitra, A., 2019, Kemoterapi Adjuvan pada Kanker Kolorektal, Jurnal kesehatan Andalas, 8(1), 51-58. CrossRef

Simos, T., Georgopoulou, U., Thyphronitis, G., Koskinas, J., and Papaloukas, C., 2015, Analysis of protein interaction networks for the detection of candidate hepatitis B and C biomarkers, IEEE J Biomed Health Inform, 19(1), 181-189. CrossRef

Suherlan, S., Rohayah, R., and Fakih, T.M, 2021, Uji Aktivitas Antikanker Payudara Senyawa Andrografolida dari Tumbuhan Sambiloto (Andrographis paniculata (Burm F) Ness.) Terhadap Human Epidermal Growth Factor Receptor2 (HER-2) Secara in silico, Jurnal Ilmiah Farmasyifa, 4(2), 39-50. CrossRef