Network Pharmacology Analysis of Secondary Metabolites of Ciplukan (Physalis angulata L.) Against Lung Cancer
Azka Khoirunnisa(1), Ahmad Shobrun Jamil(2*), Muhammad Artabah Muchlisin(3)
(1) Program Studi Farmasi, Fakultas Ilmu Kesehatan, Universitas Muhammadiyah Malang
(2) Program Studi Farmasi, Fakultas Ilmu Kesehatan, Universitas Muhammadiyah Malang
(3) Program Studi Farmasi, Fakultas Ilmu Kesehatan, Universitas Muhammadiyah Malang
(*) Corresponding Author
Abstract
Lung cancer is the most common and high-risk type of cancer. Ciplukan (Physalis angulata L.) has antibacterial, anti-inflammatory, and anticancer activities, as well as cytotoxic ability and inhibits cancer cell growth. Research that discusses the molecular cellular mechanism of P. angulata's potential as an anti-lung cancer has not been widely informed, especially on the network pharmacology aspect of this plant's active compounds. This study reveals the prediction of the molecular mechanism of active compounds of P. angulata as anti-lung cancer using several tools including: Compound database retrieval with Knapsack and PubChem. Absorption Distribution Metabolism and Excretion (ADME) screening with SwissADME. Target protein identification with Gene Card, SwissTargetPrediction and Venny Diagram. Network pharmacology construction with String-DB and Cytoscape. Network pharmacology analysis using Gene Ontology (GO), and Cellular Component and Molecular Function. Based on the results of the analysis of P. angulata protein potential based on Maximal Clique Centrality (MCC) on CytoHubba in Cytoscape application, it shows that the Protein-protein Interaction (PPI) network has 10 main targets, namely ERBB2, KRAS, TP53, PTEN, CDKN2A, NRAS, PIK3CA, BRAF, NF1, and EGFR which interact with each other to regulate cell growth, differentiation, and survival. The results of this study can be concluded that the secondary metabolite compounds of P. angulata have the potential to control and alternative for lung cancer therapy.
Keywords
Full Text:
PDFReferences
Afrăsânie, V., Marinca, M., Gafton, B., Alexa-Stratulat, T., Rusu, A., Froicu, E., Sur, D., Lungulescu, C. V., Popovici, L., Lefter, A., Afrăsânie, I., Ivanov, A., Miron, L., & Rusu, C. (2023). Clinical, Pathological and Molecular Insights on KRAS, NRAS, BRAF, PIK3CA and TP53 Mutations in Metastatic Colorectal Cancer Patients from Northeastern Romania. International Journal of Molecular Sciences, 24(16), 12679.
Al-Shamsi, H. O., Jones, J., Fahmawi, Y., Dahbour, I., Tabash, A., Abdel-Wahab, R., Abousamra, A. O. S., Shaw, K. R., Xiao, L., Hassan, M. M., Kipp, B. R., Kopetz, S., Soliman, A. S., McWilliams, R. R., & Wolff, R. A. (2016). Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer: determination of frequency and distribution pattern. Journal of Gastrointestinal Oncology, 7(6), 882–902.
Arruda, J., Rocha, N., Santos, E., Ferreira, L., Bello, M., Penido, C., Costa, T., Santos, J., Ribeiro, I., Tomassini, T., & Faria, R. (2021). Physalin pool from Physalis angulata L. leaves and physalin D inhibit P2X7 receptor function in vitro and acute lung injury in vivo. Biomedicine & Pharmacotherapy, 142, 112006.
Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7(1).
Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2024). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.who.int/today, accessed [14 February 2024].
Franco LA, Matiz GE, Calle J, Pinzón R, Ospina LF. 2007. [Antiinflammatory activity of extracts and fractions obtained from Physalis peruviana L. calyces] Biomedica 27(1):110–115.
Grassi, F., & De Ponte Conti, B. (2021). The P2X7 receptor in tumor immunity. Frontiers in Cell and Developmental Biology, 9.
Hadiyanti, N., Supriyadi, S., & Pardono, P. (2018). Keragaman beberapa tumbuhan ciplukan (Physalis spp.) di lereng gunung kelud, jawa timur. Berita Biologi, 17(2), 135-146.
Hseu, Y. C., Wu, C. R., Chang, H. W., Kumar, K. S., Lin, M. K., Chen, C. S., ... & Yang, H. L. (2011). Inhibitory effects of Physalis angulata on tumor metastasis and angiogenesis. Journal of Ethnopharmacology, 135(3), 762-771.
Hsieh W. T., K. Y. Huang, H. Y. Lin and J. G. Chung. 2006. Physalis angulata induced G2/M phase arrest in human breast cancer cells. Food Chem. Toxicol. 44(7): 974–983.
Januário, A. H., Filho, E. R., Pietro, R. C. L. R., Kashima, S., Sato, D. N., & França, S. C. (2002). Antimycobacterial physalins from Physalis angulata L.(Solanaceae). Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives, 16(5), 445-448.
Lena, N., Jamil, A. S., Muchlisin, M. A., & Almutahrihan, I. F. (2023). Analisis Jejaring Farmakologi Tanaman Jati Belanda (Guazuma ulmifolia Lamk.) Sebagai Imunomodulator. Journal of Islamic Pharmacy, 8(1), 1-6.
Li, Q., Zhu, X., Song, W., Peng, X., & Zhao, R. (2020). The P2X7 purinergic receptor: a potential therapeutic target for lung cancer. Journal of Cancer Research and Clinical Oncology, 146(11), 2731–2741.
Liu, W., Liu, J., & Rajapakse, J. C. (2018). Gene ontology enrichment improves performances of functional similarity of genes. Scientific reports, 8(1), 12100.
Mai, Y., Guo, Z., Yin, W., Zhong, N., Dicpinigaitis, P. V., & Chen, R. (2021). P2X receptors: Potential therapeutic targets for symptoms associated with lung cancer — a mini review. Frontiers in Oncology, 11.
Mathavan, S., Kue, C. S., & Kumar, S. (2021). Identification of potential candidate genes for lip and oral cavity cancer using network analysis. Genomics & Informatics/Genomics & Informatics, 19(1), e4.
NCBI - ERBB2 erb-b2 receptor tyrosine kinase 2 [Homo sapiens (human)]. (2024, May 12). National Library of Medicine. National Center of Biotechnology Information. https://www.ncbi.nlm.nih.gov/gene/2064
Novitasari, A., Rohmawaty, E., & Rosdianto, A. (2024). Physalis angulata Linn. as a medicinal plant (Review). Biomedical Reports, 20(3).
Ooi, K. L., Muhammad, T. S. T., Lim, C. H., & Sulaiman, S. F. (2010). Apoptotic Effects of Physalis minima L. Chloroform Extract in Human Breast Carcinoma T-47D Cells Mediated by c-myc-, p53-, and Caspase-3-Dependent Pathways. Integrative Cancer Therapies, 9(1), 73–83.
Palmer, N., Talib, S. Z. A., Ratnacaram, C. K., Low, D., Bisteau, X., Lee, J. H. S., Pfeiffenberger, E., Wollmann, H., Tan, J. H. L., Wee, S., Sobota, R., Gunaratne, J., Messerschmidt, D. M., Guccione, E., & Kaldis, P. (2019). CDK2 regulates the NRF1/Ehmt1 axis during meiotic prophase I. ˜the œJournal of Cell Biology/˜the œJournal of Cell Biology, 218(9), 2896–2918.
Pires, D. E., Blundell, T. L., & Ascher, D. B. (2015). pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of medicinal chemistry, 58(9), 4066-4072.
Saridaki, Z., Tzardi, M., Papadaki, C., Sfakianaki, M., Pega, F., Kalikaki, A., Tsakalaki, E., Trypaki, M., Messaritakis, I., Stathopoulos, E., Mavroudis, D., Georgoulias, V., & Souglakos, J. (2011). Impact of KRAS, BRAF, PIK3CA mutations, PTEN, AREG, EREG expression and skin rash in ≥2nd line Cetuximab-Based therapy of colorectal cancer patients. PloS One, 6(1), e15980.
Sclafani, F., Wilson, S. H., Cunningham, D., De Castro, D. G., Kalaitzaki, E., Begum, R., Wotherspoon, A., Capdevila, J., Glimelius, B., Roselló, S., Thomas, J., Tait, D., Brown, G., Oates, J., & Chau, I. (2019). Analysis of KRAS, NRAS, BRAF, PIK3CA and TP53 mutations in a large prospective series of locally advanced rectal cancer patients. International Journal of Cancer, 146(1), 94–102.
Soares M. B., D. Brustolim, L. A. Santos, M. C. Bellintani, F. P. Paiva, Y. M. Ribeiro, T. C. Tomassini and R. Ribeiro Dos Santos. 2006. Physalins B, F and G, seco-steroids purified from Physalis angulata L., inhibit lymphocyte function and allogeneic transplant rejection. Int Immunopharmacol. 6(3): 408–414.
Sunaryo, H., Hikmawanti, N. P. E., & Listyaningrum, H. A. (2018, August). Study in Activity Combination of Physalis Angulata and Hibiscus sabdariffa in 70% Ethanol Extract to Decrease Blood Sugar Levels and Histopathology of Pancreas Langerhans Island in Alloxan Induced Diabetic Rats. In Proceedings of the 1st Muhammadiyah International Conference on Health and Pharmaceutical Development (MICH-PhD 2018), East Jakarta, Indonesia (pp. 10-11).
Swaney, D. L., Ramms, D. J., Wang, Z., Park, J., Goto, Y., Soucheray, M., Bhola, N., Kim, K., Zheng, F., Zeng, Y., McGregor, M., Herrington, K. A., O’Keefe, R., Jin, N., VanLandingham, N. K., Foussard, H., Von Dollen, J., Bouhaddou, M., Jimenez-Morales, D., . . . Krogan, N. J. (2021). A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity. Science, 374(6563).
Tshikhudo, P. P., Mabhaudhi, T., Koorbanally, N. A., Mudau, F. N., Caceres, E. O. A., Popa, D., Calina, D., & Sharifi‐Rad, J. (2024). Anticancer potential of Β‐Carboline alkaloids: an updated mechanistic overview. Chemistry & Biodiversity, 21(2).
Ua, A. M. S., Marpaung, E. S. K., Ong, J., Savinka, M., Nurhaliza, P., & Ningsih, R. Y. (2023). Penggunaan Bahasa Pemrograman Python Dalam Analisis Faktor Penyebab Kanker Paru-Paru. Jurnal Publikasi Teknik Informatika, 2(2), 88-99.
World Health Organization: WHO & World Health Organization: WHO. (2023, June 26). Lung cancer. https://www.who.int/news-room/fact-sheets/detail/lung-cancer?gad_source=1&gclid=CjwKCAiArLyuBhA7EiwA-qo80COeQm9yQj9OkpiYzaRzttuYQaAedlpCnIudvUPZ6yk2fm7YLcErKxoCYB0QAvD_BwE
Wu S. J., L. T. Ng, D. L. Lin, S. N. Huang, S. S. Wang and C. C. Lin. 2004. Physalis peruviana extract induces apoptosis in human Hep G2 cells through CD95/CD95L system and the mitochondrial signaling transduction pathway. Cancer Lett. 215(2):199–208.
Zhong, S., Tian, L., Li, C., Storch, K. F., & Wong, W. H. (2004). Comparative analysis of gene sets in the gene ontology space under the multiple hypothesis testing framework. Proceedings - 2004 IEEE Computational Systems Bioinformatics Conference, 2004. CSB 2004., 425–435.
DOI: https://doi.org/10.22146/farmaseutik.v20i2.96275
Article Metrics
Abstract views : 1558 | views : 2115Refbacks
- There are currently no refbacks.