Potential of Bioactive Compounds In Coleus amboinicus, Lour., Leaves Against Breast Cancer By Assessment Using A Network Pharmacology Approach and Cytotoxic Test

Authors

DOI:

https://doi.org/10.47352/jmans.2774-3047.246

Keywords:

Coleus amboinicus, bioinformatics, pharmacology network, breast cancer, MCF-7, STAT3

Abstract

Breast cancer is a disease that significantly contributes to global women death. The study aims to conduct in vitro activity testing and assessment with a bioinformatics approach using a pharmacological network of bioactive compounds from bangun-bangun (Coleus amboinicus) leaves extract as a breast cancer drug. The methods used are extraction of bioactive compounds by maceration and partition, identification and analysis of bioactive compounds using the Liquid Chromatography High-Resolution Mass Spectrometry (LC-HRMS) instrument, cytotoxic testing of breast cancer cells (MCF-7) and normal cells (CV-1) with the MTT method, and assessment with a bioinformatics approach through a network pharmacology. The results of the cytotoxic test of ethyl acetate extract provided better activity with IC50 value of 102.30 and 457.09 µg/mL against MCF-7 cancer cells and CV-1 normal cells. The selectivity index value of 4.23 indicates the potential for further development in the treatment of breast cancer. The results of the analysis of chemical compound content show various types of potential bioactive compounds as breast cancer anticancer; assessment of the bioinformatics approach through networks pharmacology with pathways in cancer provides predictions of signal transducer and activator of transcription 3 (STAT3) protein as the main therapeutic mechanism target in breast cancer treatment. This study provides initial information for further research on testing and utilizing bioactive compounds from C. amboinicus leaves as an alternative treatment for breast cancer.

References

[1] N. Azamjah, Y. Soltan-Zadeh, and F. Zayeri. (2019). "Global Trend of Breast Cancer Mortality Rate: A 25-Year Study". Asian Pacific Journal of Cancer Prevention. 20 (7): 2015-2020. 10.31557/APJCP.2019.20.7.2015.

DOI: https://doi.org/10.31557/APJCP.2019.20.7.2015

[2] Y. S. Sun, Z. Zhao, Z. N. Yang, F. Xu, H. J. Lu, Z. Y. Zhu, W. Shi, J. Jiang, P. P. Yao, and H. P. Zhu. (2017). "Risk Factors and Preventions of Breast Cancer". International Journal of Biological Sciences. 13 (11): 1387-1397. 10.7150/ijbs.21635.

DOI: https://doi.org/10.7150/ijbs.21635

[3] C. E. DeSantis, J. Ma, M. M. Gaudet, L. A. Newman, K. D. Miller, A. Goding Sauer, A. Jemal, and R. L. Siegel. (2019). "Breast cancer statistics, 2019". CA: A Cancer Journal for Clinicians. 69 (6): 438-451. 10.3322/caac.21583.

DOI: https://doi.org/10.3322/caac.21583

[4] Z. Chen, L. Xu, W. Shi, F. Zeng, R. Zhuo, X. Hao, and P. Fan. (2020). "Trends of female and male breast cancer incidence at the global, regional, and national levels, 1990-2017". Breast Cancer Research and Treatment. 180 (2): 481-490. 10.1007/s10549-020-05561-1.

DOI: https://doi.org/10.1007/s10549-020-05561-1

[5] S. Anwar, A. Almatroudi, M. A. Alsahli, M. A. Khan, A. A. Khan, and A. H. Rahmani. (2020). "Natural Products: Implication in Cancer Prevention and Treatment through Modulating Various Biological Activities". Anti-Cancer Agents in Medicinal Chemistry. 20 (17): 2025-2040. 10.2174/1871520620666200705220307.

DOI: https://doi.org/10.2174/1871520620666200705220307

[6] S. M. Lima, R. D. Kehm, and M. B. Terry. (2021). "Global breast cancer incidence and mortality trends by region, age-groups, and fertility patterns". EClinicalMedicine. 38 : 100985. 10.1016/j.eclinm.2021.100985.

DOI: https://doi.org/10.1016/j.eclinm.2021.100985

[7] S. Lei, R. Zheng, S. Zhang, R. Chen, S. Wang, K. Sun, H. Zeng, W. Wei, and J. He. (2021). "Breast cancer incidence and mortality in women in China: temporal trends and projections to 2030". Cancer Biology and Medicine. 18 (3): 900-9. 10.20892/j.issn.2095-3941.2020.0523.

DOI: https://doi.org/10.20892/j.issn.2095-3941.2020.0523

[8] S. Lei, R. Zheng, S. Zhang, S. Wang, R. Chen, K. Sun, H. Zeng, J. Zhou, and W. Wei. (2021). "Global patterns of breast cancer incidence and mortality: A population-based cancer registry data analysis from 2000 to 2020". Cancer Communication (Lond). 41 (11): 1183-1194. 10.1002/cac2.12207.

DOI: https://doi.org/10.1002/cac2.12207

[9] Y. Xu, M. Gong, Y. Wang, Y. Yang, S. Liu, and Q. Zeng. (2023). "Global trends and forecasts of breast cancer incidence and deaths". Scientific Data. 10 (1): 334. 10.1038/s41597-023-02253-5.

DOI: https://doi.org/10.1038/s41597-023-02253-5

[10] C. Luo, N. Li, B. Lu, J. Cai, M. Lu, Y. Zhang, H. Chen, and M. Dai. (2022). "Global and regional trends in incidence and mortality of female breast cancer and associated factors at national level in 2000 to 2019". Chinese medical journal (English). 135 (1): 42-51. 10.1097/CM9.0000000000001814.

DOI: https://doi.org/10.1097/CM9.0000000000001814

[11] E. B. Yahya and A. M. Alqadhi. (2021). "Recent trends in cancer therapy: A review on the current state of gene delivery". Life Sciences. 269 : 119087. 10.1016/j.lfs.2021.119087.

DOI: https://doi.org/10.1016/j.lfs.2021.119087

[12] J. B. Vo, C. Ramin, A. Barac, A. Berrington de Gonzalez, and L. Veiga. (2022). "Trends in heart disease mortality among breast cancer survivors in the US, 1975-2017". Breast Cancer Research and Treatment. 192 (3): 611-622. 10.1007/s10549-022-06515-5.

DOI: https://doi.org/10.1007/s10549-022-06515-5

[13] M. J. Elliott, B. Wilson, and D. W. Cescon. (2022). "Current Treatment and Future Trends of Immunotherapy in Breast Cancer". Current Cancer Drug Targets. 22 (8): 667-677. 10.2174/1568009622666220317091723.

DOI: https://doi.org/10.2174/1568009622666220317091723

[14] M. I. Khan, A. Bouyahya, N. E. L. Hachlafi, N. E. Menyiy, M. Akram, S. Sultana, G. Zengin, L. Ponomareva, M. A. Shariati, O. A. Ojo, S. Dall'Acqua, and T. C. Elebiyo. (2022). "Anticancer properties of medicinal plants and their bioactive compounds against breast cancer: a review on recent investigations". Environmental Science and Pollution Research. 29 (17): 24411-24444. 10.1007/s11356-021-17795-7.

DOI: https://doi.org/10.1007/s11356-021-17795-7

[15] W. Haryadi, K. Gurning, and E. Astuti. (2024). "Molecular target identification of two Coleus amboinicus leaf isolates toward lung cancer using a bioinformatic approach and molecular docking-based assessment". Journal of Applied Pharmaceutical Science.  10.7324/japs.2024.164753.

DOI: https://doi.org/10.7324/JAPS.2024.164753

[16] K. Gurning and W. Haryadi. (2022). "Potential antioxidants of secondary metabolite isolates ethyl acetate fraction Coleus amboinicus Lour. Leaves". ScienceRise: Pharmaceutical Science. 5 (39): 100-105. 10.15587/2519-4852.2022.266401.

DOI: https://doi.org/10.15587/2519-4852.2022.266401

[17] K. Gurning, W. Haryadi, and H. Sastrohamidjojo. (2021). "Isolation And Characterization Of Antioxidant Compounds Of Bangun-Bangun (Coleus Amboinicus, L.) Leaves From North Sumatera, Indonesia". Rasayan Journal of Chemistry. 14 (01): 248-253. 10.31788/rjc.2021.1416077.

DOI: https://doi.org/10.31788/RJC.2021.1416077

[18] K. Gurning. (2020). "Identification of secondary metabolic and test of activity ethyl acetate fraction of bangunâ¬- bangun (coleus amboinicus lour.) Leaves as antioxidant". BIOLINK (Jurnal Biologi Lingkungan Industri Kesehatan). 7 (1): 117-122. 10.31289/biolink.v7i1.3732.

DOI: https://doi.org/10.31289/biolink.v7i1.3732

[19] K. Gurning. (2020). "Determination antioxidant activities methanol extracts of bangun-bangun (Coleus amboinicus L.) Leaves with DPPH method". Jurnal Pendidikan Kimia. 12 (2): 62-69. 10.24114/jpkim.v12i2.19397.

DOI: https://doi.org/10.24114/jpkim.v12i2.19397

[20] S. Slusarczyk, A. Cieslak, Y. R. Yanza, M. Szumacher-Strabel, Z. Varadyova, M. Stafiniak, D. Wojnicz, and A. Matkowski. (2021). "Phytochemical Profile and Antioxidant Activities of Coleus amboinicus Lour. Cultivated in Indonesia and Poland". Molecules. 26 (10). 10.3390/molecules26102915.

DOI: https://doi.org/10.3390/molecules26102915

[21] K. Gurning, S. Suratno, E. Astuti, and W. Haryadi. (2024). "Untargeted LC/HRMS Metabolomics Analysis and Anticancer Activity Assay on MCF-7 and A549 Cells from Coleus amboinicus Lour Leaf Extract". Iranian Journal of Pharmaceutical Research. 23 (1): e143494. 10.5812/ijpr-143494.

DOI: https://doi.org/10.5812/ijpr-143494

[22] J. M. Onyancha, N. K. Gikonyo, S. W. Wachira, P. G. Mwitari, and M. M. Gicheru. (2018). "Anticancer activities and safety evaluation of selected Kenyan plant extracts against breast cancer cell lines". Journal of Pharmacognosy and Phytotherapy. 10 (2): 21-26. 10.5897/jpp2017.0465.

DOI: https://doi.org/10.5897/JPP2017.0465

[23] N. Z. Ismail, Z. Md Toha, M. Muhamad, N. N. S. Nik Mohamed Kamal, N. N. Mohamad Zain, and H. Arsad. (2020). "Antioxidant Effects, Antiproliferative Effects, and Molecular Docking of Clinacanthus nutans Leaf Extracts". Molecules. 25 (9).  10.3390/molecules25092067.

DOI: https://doi.org/10.3390/molecules25092067

[24] R. Islamie, I. Iksen, B. C. Buana, K. Gurning, H. D. Syahputra, and H. S. Winata. (2022). "Construction of network pharmacology-based approach and potential mechanism from major components of Coriander sativum L. against COVID-19". Pharmacia. 69 (3): 689-697. 10.3897/pharmacia.69.e84388.

DOI: https://doi.org/10.3897/pharmacia.69.e84388.figure3

[25] M. A. Basar, M. F. Hosen, B. Kumar Paul, M. R. Hasan, S. M. Shamim, and T. Bhuyian. (2023). "Identification of drug and protein-protein interaction network among stress and depression: A bioinformatics approach". Informatics in Medicine Unlocked. 3710.1016/j.imu.2023.101174.

DOI: https://doi.org/10.1016/j.imu.2023.101174

[26] Y. Wang, Y. Zhang, Y. Wang, X. Shu, C. Lu, S. Shao, X. Liu, C. Yang, J. Luo, and Q. Du. (2021). "Using Network Pharmacology and Molecular Docking to Explore the Mechanism of Shan Ci Gu (Cremastra appendiculata) Against Non-Small Cell Lung Cancer". Frontiers in Chemistry. 9 : 682862. 10.3389/fchem.2021.682862.

DOI: https://doi.org/10.3389/fchem.2021.682862

[27] Y. S. Kurniawan, K. Gurning, I. Iksen, and A. Bikharudin. (2024). "Fight for Cancer Diseases using Natural Compounds and Their Semisynthetic Derivatives". Bioactivities. 2 (2): 1-22. 10.47352/bioactivities.2963-654X.221.

DOI: https://doi.org/10.47352/bioactivities.2963-654X.221

[28] D. Adisty Ridha, S. Eti Nurwening, and Mustofa. (2020). "Cytotoxicity of ((E)-1-(4-aminophenyl)-3-phenylprop-2-en-1-one)) on HeLa cell line". Indonesian Journal of Pharmacology and Therapy. 1 (2). 10.22146/ijpther.606.

DOI: https://doi.org/10.22146/ijpther.606

[29] Y. S. Kurniawan, T. Indriani, H. Amrulloh, L. C. Adi, A. C. Imawan, K. T. A. Priyangga, and E. Yudha. (2023). "The Journey of Natural Products: From Isolation Stage to Drug’s Approval in Clinical Trials". Bioactivities. 1 (2): 43-60. 10.47352/bioactivities.2963-654X.190.

DOI: https://doi.org/10.47352/bioactivities.2963-654X.190

[30] K. Ganesan, B. Du, and J. Chen. (2022). "Effects and mechanisms of dietary bioactive compounds on breast cancer prevention". Pharmacological Research. 178 : 105974. 10.1016/j.phrs.2021.105974.

DOI: https://doi.org/10.1016/j.phrs.2021.105974

[31] A. B. Shirode, D. J. Bharali, S. Nallanthighal, J. K. Coon, S. A. Mousa, and R. Reliene. (2015). "Nanoencapsulation of pomegranate bioactive compounds for breast cancer chemoprevention". International Journal of Nanomedicine. 10 : 475-84. 10.2147/IJN.S65145.

DOI: https://doi.org/10.2147/IJN.S65145

[32] S. S. Dahham, Y. M. Tabana, M. A. Iqbal, M. B. Ahamed, M. O. Ezzat, A. S. Majid, and A. M. Majid. (2015). "The Anticancer, Antioxidant and Antimicrobial Properties of the Sesquiterpene beta-Caryophyllene from the Essential Oil of Aquilaria crassna". Molecules. 20 (7): 11808-29. 10.3390/molecules200711808.

DOI: https://doi.org/10.3390/molecules200711808

[33] N. To’Bungan, R. Pratiwi, S. Widyarini, and L. H. Nugroho. (2022). "Cytotoxicity extract and fraction of knobweed (Hyptis capitata) and its effect on migration and apoptosis of T47D cells". Biodiversitas Journal of Biological Diversity. 23 (1).  10.13057/biodiv/d230162.

DOI: https://doi.org/10.13057/biodiv/d230162

[34] A. Flippen, I. A. Khasabova, D. A. Simone, and S. G. Khasabov. (2024). "Systemic administration of Resolvin D1 reduces cancer-induced bone pain in mice: Lack of sex dependency in pain development and analgesia". Cancer Medicine. 13 (15): e70077. 10.1002/cam4.70077.

DOI: https://doi.org/10.1002/cam4.70077

[35] D. Mattoscio, E. Isopi, A. Lamolinara, S. Patruno, A. Medda, F. De Cecco, S. Chiocca, M. Iezzi, M. Romano, and A. Recchiuti. (2021). "Resolvin D1 reduces cancer growth stimulating a protective neutrophil-dependent recruitment of anti-tumor monocytes". Journal of Experimental and Clinical Cancer Research. 40 (1): 129. 10.1186/s13046-021-01937-3.

DOI: https://doi.org/10.1186/s13046-021-01937-3

[36] I. A. Khasabova, M. Y. Golovko, S. A. Golovko, D. A. Simone, and S. G. Khasabov. (2020). "Intrathecal administration of Resolvin D1 and E1 decreases hyperalgesia in mice with bone cancer pain: Involvement of endocannabinoid signaling". Prostaglandins Other Lipid Mediat. 151 : 106479. 10.1016/j.prostaglandins.2020.106479.

DOI: https://doi.org/10.1016/j.prostaglandins.2020.106479

[37] L. Sun, Y. Wang, L. Wang, B. Yao, T. Chen, Q. Li, Z. Liu, R. Liu, Y. Niu, T. Song, Q. Liu, and K. Tu. (2019). "Resolvin D1 prevents epithelial-mesenchymal transition and reduces the stemness features of hepatocellular carcinoma by inhibiting paracrine of cancer-associated fibroblast-derived COMP". Journal of Experimental and Clinical Cancer Research. 38 (1): 170. 10.1186/s13046-019-1163-6.

DOI: https://doi.org/10.1186/s13046-019-1163-6

[38] E. C. Dominguez, R. Phandthong, M. Nguyen, A. Ulu, S. Guardado, S. Sveiven, P. Talbot, and T. M. Nordgren. (2022). "Aspirin-Triggered Resolvin D1 Reduces Chronic Dust-Induced Lung Pathology without Altering Susceptibility to Dust-Enhanced Carcinogenesis". Cancers (Basel). 14 (8). 10.3390/cancers14081900.

DOI: https://doi.org/10.3390/cancers14081900

[39] T. Toyama, M. Tahara, K. Nagamune, K. Arimitsu, Y. Hamashima, N. M. Palacpac, H. Kawaide, T. Horii, and K. Tanabe. (2012). "Gibberellin biosynthetic inhibitors make human malaria parasite Plasmodium falciparum cells swell and rupture to death". PLoS One. 7 (3): e32246. 10.1371/journal.pone.0032246.

DOI: https://doi.org/10.1371/journal.pone.0032246

[40] S.-y. Zhu, F.-z. Luo, and P.-H. Sun. (2020). "Synthesis and antitumor activity of novel gibberellin derivatives with tetracyclic diterpenoid skeletons". Medicinal Chemistry Research. 29 (8): 1341-1354. 10.1007/s00044-020-02551-2.

DOI: https://doi.org/10.1007/s00044-020-02551-2

[41] J. M. Khaled, N. S. Alharbi, R. A. Mothana, S. Kadaikunnan, and A. S. Alobaidi. (2021). "Biochemical Profile by GC-MS of Fungal Biomass Produced from the Ascospores of Tirmania nivea as a Natural Renewable Resource". Journal of Fungi (Basel). 7 (12). 10.3390/jof7121083.

DOI: https://doi.org/10.3390/jof7121083

[42] C. Wolff, C. Zoschke, S. K. Kalangi, P. Reddanna, and M. Schafer-Korting. (2019). "Tumor microenvironment determines drug efficacy in vitro - apoptotic and anti-inflammatory effects of 15-lipoxygenase metabolite, 13-HpOTrE". European Journal of Pharmaceutics and Biopharmaceutics. 142 : 1-7. 10.1016/j.ejpb.2019.06.003.

DOI: https://doi.org/10.1016/j.ejpb.2019.06.003

[43] S. M. Clemente, O. H. Martinez-Costa, M. Monsalve, and A. K. Samhan-Arias. (2020). "Targeting Lipid Peroxidation for Cancer Treatment". Molecules. 25 (21).  10.3390/molecules25215144.

DOI: https://doi.org/10.3390/molecules25215144

[44] D. Lv, Y. Zou, Z. Zeng, H. Yao, S. Ding, Y. Bian, L. Wen, and X. Xie. (2020). "Comprehensive metabolomic profiling of osteosarcoma based on UHPLC-HRMS". Metabolomics. 16 (12): 120. 10.1007/s11306-020-01745-4.

DOI: https://doi.org/10.1007/s11306-020-01745-4

[45] H. Tallima and R. El Ridi. (2023). "Mechanisms of Arachidonic Acid In Vitro Tumoricidal Impact". Molecules. 28 (4). 10.3390/molecules28041727.

DOI: https://doi.org/10.3390/molecules28041727

[46] L. Ouldamer, M. L. Jourdan, M. Pinault, F. Arbion, and C. Goupille. (2022). "Accumulation of Arachidonic Acid, Precursor of Pro-Inflammatory Eicosanoids, in Adipose Tissue of Obese Women: Association with Breast Cancer Aggressiveness Indicators". Biomedicines. 10 (5). 10.3390/biomedicines10050995.

DOI: https://doi.org/10.3390/biomedicines10050995

[47] W. Li, X. Guo, C. Chen, and J. Li. (2022). "The prognostic value of arachidonic acid metabolism in breast cancer by integrated bioinformatics". Lipids in Health and Disease. 21 (1): 103. 10.1186/s12944-022-01713-y.

DOI: https://doi.org/10.1186/s12944-022-01713-y

[48] C. Cantonero, J. Sanchez-Collado, J. J. Lopez, G. M. Salido, J. A. Rosado, and P. C. Redondo. (2020). "Arachidonic Acid Attenuates Cell Proliferation, Migration and Viability by a Mechanism Independent on Calcium Entry". International Journal of Molecular Sciences. 21 (9). 10.3390/ijms21093315.

DOI: https://doi.org/10.3390/ijms21093315

[49] M. L. Luo, W. Huang, H. P. Zhu, C. Peng, Q. Zhao, and B. Han. (2022). "Advances in indole-containing alkaloids as potential anticancer agents by regulating autophagy". Biomedicine and Pharmacotherapy. 149 : 112827. 10.1016/j.biopha.2022.112827.

DOI: https://doi.org/10.1016/j.biopha.2022.112827

[50] T. D. Hubbard, I. A. Murray, and G. H. Perdew. (2015). "Indole and Tryptophan Metabolism: Endogenous and Dietary Routes to Ah Receptor Activation". Drug Metabolism and Disposition. 43 (10): 1522-35. 10.1124/dmd.115.064246.

DOI: https://doi.org/10.1124/dmd.115.064246

[51] D. Xu and Z. Xu. (2020). "Indole Alkaloids with Potential Anticancer Activity". Current Topics in Medicinal Chemistry. 20 (21): 1938-1949. 10.2174/1568026620666200622150325.

DOI: https://doi.org/10.2174/1568026620666200622150325

[52] A. Dhiman, R. Sharma, and R. K. Singh. (2022). "Target-based anticancer indole derivatives and insight into structure‒activity relationship: A mechanistic review update (2018-2021)". Acta Pharmaceutica Sinica B. 12 (7): 3006-3027. 10.1016/j.apsb.2022.03.021.

DOI: https://doi.org/10.1016/j.apsb.2022.03.021

[53] M. Wicinski, A. Fajkiel-Madajczyk, Z. Kurant, S. Gajewska, D. Kurant, M. Kurant, and M. Sousak. (2024). "Can Asiatic Acid from Centella asiatica Be a Potential Remedy in Cancer Therapy?-A Review". Cancers (Basel). 16 (7). 10.3390/cancers16071317.

DOI: https://doi.org/10.3390/cancers16071317

[54] S. Dutta, P. Chakraborty, S. Basak, S. Ghosh, N. Ghosh, S. Chatterjee, S. Dewanjee, and P. C. Sil. (2022). "Synthesis, characterization, and evaluation of in vitro cytotoxicity and in vivo antitumor activity of asiatic acid-loaded poly lactic-co-glycolic acid nanoparticles: A strategy of treating breast cancer". Life Sciences. 307 : 120876. 10.1016/j.lfs.2022.120876.

DOI: https://doi.org/10.1016/j.lfs.2022.120876

[55] Z. Zhu, L. Cui, J. Yang, C. T. Vong, Y. Hu, J. Xiao, G. Chan, Z. He, and Z. Zhong. (2021). "Anticancer effects of asiatic acid against doxorubicin-resistant breast cancer cells via an AMPK-dependent pathway in vitro". Phytomedicine. 92 : 153737. 10.1016/j.phymed.2021.153737.

DOI: https://doi.org/10.1016/j.phymed.2021.153737

[56] J. M. Grantz, V. P. Thirumalaikumar, A. H. Jannasch, C. Andolino, N. Taechachokevivat, L. M. Avila-Granados, and R. C. Neves. (2024). "The platelet and plasma proteome and targeted lipidome in postpartum dairy cows with elevated systemic inflammation". Scientific Reports. 14 (1): 31240. 10.1038/s41598-024-82553-x.

DOI: https://doi.org/10.1038/s41598-024-82553-x

[57] A. Kabala-Dzik, A. Rzepecka-Stojko, R. Kubina, R. D. Wojtyczka, E. Buszman, and J. Stojko. (2018). "Caffeic Acid Versus Caffeic Acid Phenethyl Ester in the Treatment of Breast Cancer MCF-7 Cells: Migration Rate Inhibition". Integrative Cancer Therapies. 17 (4): 1247-1259. 10.1177/1534735418801521.

DOI: https://doi.org/10.1177/1534735418801521

[58] M. Alam, S. Ahmed, A. M. Elasbali, M. Adnan, S. Alam, M. I. Hassan, and V. R. Pasupuleti. (2022). "Therapeutic Implications of Caffeic Acid in Cancer and Neurological Diseases". Frontiers in Oncology. 12 : 860508. 10.3389/fonc.2022.860508.

DOI: https://doi.org/10.3389/fonc.2022.860508

[59] M. Alam, G. M. Ashraf, K. Sheikh, A. Khan, S. Ali, M. M. Ansari, M. Adnan, V. R. Pasupuleti, and M. I. Hassan. (2022). "Potential Therapeutic Implications of Caffeic Acid in Cancer Signaling: Past, Present, and Future". Frontiers in Pharmacology. 13 : 845871. 10.3389/fphar.2022.845871.

DOI: https://doi.org/10.3389/fphar.2022.845871

[60] S. Mirzaei, M. H. Gholami, A. Zabolian, H. Saleki, M. V. Farahani, S. Hamzehlou, F. B. Far, S. O. Sharifzadeh, S. Samarghandian, H. Khan, A. R. Aref, M. Ashrafizadeh, A. Zarrabi, and G. Sethi. (2021). "Caffeic acid and its derivatives as potential modulators of oncogenic molecular pathways: New hope in the fight against cancer". Pharmacological Research. 171 : 105759. 10.1016/j.phrs.2021.105759.

DOI: https://doi.org/10.1016/j.phrs.2021.105759

[61] H. Rezaei-Seresht, H. Cheshomi, F. Falanji, F. Movahedi-Motlagh, M. Hashemian, and E. Mireskandari. (2019). "Cytotoxic activity of caffeic acid and gallic acid against MCF-7 human breast cancer cells: An in silico and in vitro study". Avicenna Journal of Phytomedicine. 9 (6): 574-586. 10.22038/AJP.2019.13475.

[62] G. E. Robertovna, K. D. Alexeevich, S. A. Alexeevich, G. M. Petrovna, and O. K. Kenzhebaevna. (2019). "A Traditional Medicine Plant, Onopordum acanthium L. (Asteraceae): Chemical Composition and Pharmacological Research". Plants (Basel). 8 (2). 10.3390/plants8020040.

DOI: https://doi.org/10.3390/plants8020040

[63] D. Wang, A. S. Badarau, M. K. Swamy, S. Shaw, F. Maggi, L. E. da Silva, V. Lopez, A. W. K. Yeung, A. Mocan, and A. G. Atanasov. (2019). "Arctium Species Secondary Metabolites Chemodiversity and Bioactivities". Frontiers in Plant Science. 10 : 834. 10.3389/fpls.2019.00834.

DOI: https://doi.org/10.3389/fpls.2019.00834

[64] X. Wang, Y. Yang, Y. An, and G. Fang. (2019). "The mechanism of anticancer action and potential clinical use of kaempferol in the treatment of breast cancer". Biomedicine and Pharmacotherapy. 117 : 109086. 10.1016/j.biopha.2019.109086.

DOI: https://doi.org/10.1016/j.biopha.2019.109086

[65] P. D. Thomas. (2017). "The Gene Ontology and the Meaning of Biological Function". Methods in Molecular Biology. 1446 : 15-24. 10.1007/978-1-4939-3743-1_2.

DOI: https://doi.org/10.1007/978-1-4939-3743-1_2

[66] M. Kanehisa and Y. Sato. (2020). "KEGG Mapper for inferring cellular functions from protein sequences". Protein Science. 29 (1): 28-35. 10.1002/pro.3711.

DOI: https://doi.org/10.1002/pro.3711

[67] I. Iksen, W. Witayateeraporn, T. Wirojwongchai, C. Suraphan, N. Pornputtapong, N. Singharajkomron, H. M. Nguyen, and V. Pongrakhananon. (2023). "Identifying molecular targets of Aspiletrein-derived steroidal saponins in lung cancer using network pharmacology and molecular docking-based assessments". Scientific Reports. 13 (1): 1545. 10.1038/s41598-023-28821-8.

DOI: https://doi.org/10.1038/s41598-023-28821-8

[68] K. Banerjee and H. Resat. (2016). "Constitutive activation of STAT3 in breast cancer cells: A review". International Journal of Cancer. 138 (11): 2570-8. 10.1002/ijc.29923.

DOI: https://doi.org/10.1002/ijc.29923

[69] J. Sgrignani, M. Garofalo, M. Matkovic, J. Merulla, C. V. Catapano, and A. Cavalli. (2018). "Structural Biology of STAT3 and Its Implications for Anticancer Therapies Development". International Journal of Molecular Sciences. 19 (6).  10.3390/ijms19061591.

DOI: https://doi.org/10.3390/ijms19061591

[70] R. Bansal and P. C. Acharya. (2014). "Man-made cytotoxic steroids: exemplary agents for cancer therapy". Chemical Reviews. 114 (14): 6986-7005. 10.1021/cr4002935.

DOI: https://doi.org/10.1021/cr4002935

[71] T. Gritsko, A. Williams, J. Turkson, S. Kaneko, T. Bowman, M. Huang, S. Nam, I. Eweis, N. Diaz, D. Sullivan, S. Yoder, S. Enkemann, S. Eschrich, J. H. Lee, C. A. Beam, J. Cheng, S. Minton, C. A. Muro-Cacho, and R. Jove. (2006). "Persistent activation of stat3 signaling induces survivin gene expression and confers resistance to apoptosis in human breast cancer cells". Clinical Cancer Research. 12 (1): 11-9. 10.1158/1078-0432.CCR-04-1752.

DOI: https://doi.org/10.1158/1078-0432.CCR-04-1752

[72] L. Wang, H. S. Choi, B. Lee, J. H. Choi, Y. S. Jang, and J. W. Seo. (2021). "13R,20-Dihydroxydocosahexaenoic Acid, a Novel Dihydroxy- DHA Derivative, Inhibits Breast Cancer Stemness through Regulation of the Stat3/IL-6 Signaling Pathway by Inducing ROS Production". Antioxidants (Basel). 10 (3). 10.3390/antiox10030457.

DOI: https://doi.org/10.3390/antiox10030457

[73] P. A. Z. Hasibuan, R. A. Syahputra, E. Hey-Hawkins, M. F. Lubis, A. S. Rohani, and S. A. Pahlevi. (2024). "Phytochemical composition and safety of Vernonia Amygdalina ethanolic extract with anti-colon cancer properties". Journal of Agriculture and Food Research. 16. 10.1016/j.jafr.2024.101205.

DOI: https://doi.org/10.1016/j.jafr.2024.101205

[74] H. Tang, Y. Kuang, W. Wu, B. Peng, and Q. Fu. (2023). "Quercetin inhibits the metabolism of arachidonic acid by inhibiting the activity of CYP3A4, thereby inhibiting the progression of breast cancer". Molecular Medicine. 29 (1): 127. 10.1186/s10020-023-00720-8.

DOI: https://doi.org/10.1186/s10020-023-00720-8

[75] D. Satria, P. A. Z. Hasibuan, M. Muhammad, S. B. Waruwu, R. Y. Utomo, and S. H. Ghoran. (2024). "Cytotoxic and apoptotic effect of Vernonia amygdalina Delile. fractions against Hs578t triple-negative breast cancer cell lines". Phytomedicine Plus. 4 (4). 10.1016/j.phyplu.2024.100640.

DOI: https://doi.org/10.1016/j.phyplu.2024.100640

[76] Y. Yin, Z. Wang, Y. Hu, J. Wang, Y. I. Wang, and Q. Lu. (2024). "Caffeic acid hinders the proliferation and migration through inhibition of IL-6 mediated JAK-STAT-3 signaling axis in human prostate cancer". Oncology Research. 32 (12): 1881-1890. 10.32604/or.2024.048007.

DOI: https://doi.org/10.32604/or.2024.048007

[77] M. Beytur and I. Avinca. (2021). "Molecular, Electronic, Nonlinear Optical and Spectroscopic Analysis of Heterocyclic 3-Substituted-4-(3-methyl-2-thienylmethyleneamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones: Experiment and DFT Calculations". Heterocyclic Communications. 27 (1): 1-16. 10.1515/hc-2020-0118.

DOI: https://doi.org/10.1515/hc-2020-0118

[78] T. I. Adelusi, A.-Q. K. Oyedele, I. D. Boyenle, A. T. Ogunlana, R. O. Adeyemi, C. D. Ukachi, M. O. Idris, O. T. Olaoba, I. O. Adedotun, O. E. Kolawole, Y. Xiaoxing, and M. Abdul-Hammed. (2022). "Molecular modeling in drug discovery". Informatics in Medicine Unlocked. 29. 10.1016/j.imu.2022.100880.

DOI: https://doi.org/10.1016/j.imu.2022.100880

[79] L. Bai, H. Zhou, R. Xu, Y. Zhao, K. Chinnaswamy, D. McEachern, J. Chen, C. Y. Yang, Z. Liu, M. Wang, L. Liu, H. Jiang, B. Wen, P. Kumar, J. L. Meagher, D. Sun, J. A. Stuckey, and S. Wang. (2019). "A Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo". Cancer Cell. 36 (5): 498-511 e17. 10.1016/j.ccell.2019.10.002.

DOI: https://doi.org/10.1016/j.ccell.2019.10.002

[80] S. Q. To, R. S. Dmello, A. K. Richards, M. Ernst, and A. L. Chand. (2022). "STAT3 Signaling in Breast Cancer: Multicellular Actions and Therapeutic Potential". Cancers (Basel). 14 (2). 10.3390/cancers14020429.

DOI: https://doi.org/10.3390/cancers14020429

[81] J. J. Qin, L. Yan, J. Zhang, and W. D. Zhang. (2019). "STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review". Journal of Experimental and Clinical Cancer Research. 38 (1): 195. 10.1186/s13046-019-1206-z.

DOI: https://doi.org/10.1186/s13046-019-1206-z

[82] Y. Dong, J. Chen, Y. Chen, and S. Liu. (2023). "Targeting the STAT3 oncogenic pathway: Cancer immunotherapy and drug repurposing". Biomedicine and Pharmacotherapy. 167 : 115513. 10.1016/j.biopha.2023.115513.

DOI: https://doi.org/10.1016/j.biopha.2023.115513

Published

2025-01-26

How to Cite

[1]
W. Haryadi, K. Gurning, J. Fachiroh, and E. Astuti, “Potential of Bioactive Compounds In Coleus amboinicus, Lour., Leaves Against Breast Cancer By Assessment Using A Network Pharmacology Approach and Cytotoxic Test”, J. Multidiscip. Appl. Nat. Sci., vol. 5, no. 1, pp. 267–287, Jan. 2025.

Funding data