REVIEW ARTICLE: POTENSI SENYAWA LUTEOLIN DALAM MENGATASI PENYAKIT KANKER PAYUDARA (Carcinoma mammae) MELALUI PENDEKATAN IN SILICO DENGAN STUDI MOLECULAR DOCKING
Isi Artikel Utama
Kanker payudara merupakan salah satu jenis kanker dengan prevalensi tinggi di dunia, termasuk di Indonesia. Pengobatan konvensional seperti kemoterapi masih menimbulkan banyak efek samping, sehingga diperlukan alternatif terapi yang lebih efektif dan minim toksisitas. Luteolin, senyawa flavonoid yang ditemukan dalam berbagai tanaman, telah menunjukkan potensi sebagai agen antikanker melalui mekanisme induksi apoptosis, penghambatan angiogenesis, dan modulasi jalur pensinyalan sel kanker. Tujuan dari kajian ini adalah untuk mengevaluasi potensi luteolin sebagai agen antikanker payudara melalui pendekatan in silico dengan metode molecular docking. Kajian ini menggunakan metode studi literatur sistematis dari enam artikel ilmiah yang dipublikasikan antara tahun 2021-2024, menggunakan database seperti PubMed, ScienceDirect, dan Google Scholar. Hasil kajian menunjukkan bahwa luteolin memiliki afinitas ikatan yang tinggi terhadap berbagai target molekuler penting dalam kanker payudara seperti aromatase (3EQM), ER-alpha, SGK1, dan PLK1. Luteolin juga menunjukkan aktivitas biologis yang mencakup induksi apoptosis, penghambatan proliferasi dan metastasis sel kanker, serta peningkatan efektivitas saat diformulasikan dengan nanopartikel ZnO. Namun, analisis toksisitas in silico mengindikasikan adanya potensi karsinogenik genotoksik, meskipun tidak menunjukkan sifat toksik secara nongenotoksik. Luteolin memiliki potensi sebagai antikanker payudara multitarget dengan mekanisme kerja yang kompleks dan luas. Dengan demikian, diperlukan penelitian lebih lanjut secara in vitro dan in vivo untuk memastikan keamanan dan efektivitasnya.
Kata kunci: Kanker payudara, luteolin, molecular docking.
Breast cancer is one type of cancer with a high prevalence in the world, including in Indonesia. Conventional treatments such as chemotherapy still cause many side effects, so alternative therapies that are more effective and minimize toxicity are needed. Luteolin, a flavonoid compound found in various plants, has shown potential as an anticancer agent through the mechanisms of apoptosis induction, angiogenesis inhibition, and modulation of cancer cell signaling pathways. The purpose of this study is to evaluate the potential of luteolin as a breast anticancer agent through an in silico approach with molecular docking method. This study uses a systematic literature study method from six scientific articles published between 2021-2024, using databases such as PubMed, ScienceDirect, and Google Scholar. The results showed that luteolin has high binding affinity to various important molecular targets in breast cancer such as aromatase (3EQM), ER-alpha, SGK1, and PLK1. Luteolin also exhibits biological activities that include induction of apoptosis, inhibition of cancer cell proliferation and metastasis, and enhanced effectiveness when formulated with ZnO nanoparticles. However, in silico toxicity analysis indicated genotoxic carcinogenic potential, although it did not show nongenotoxic properties. Luteolin has potential as a multitarget breast anticancer with a complex and broad mechanism of action. Thus, further in vitro and in vivo studies are needed to ensure its safety and clinical effectiveness.
Keywords: Breast cancer, luteolin, molecular docking.
Barokah, E.K., Saputri, M.I., Saputri, R.D., Edita, S.Y.P., and Okranniva, Amalia Putri Kurniawati, N., 2024. Studi Molekular Docking Kandungan Senyawa Parsley (Petroselinum crispum) Sebagai Inhibitor Protein 3PE1 Untuk Terapi Kanker Kulit Melanoma Secara In Silico. Prosiding Seminar Nasional Farmasi, 1, 75–86.
Cook, M.T., Mafuvadze, B., Besch-Williford, C., Ellersieck, M.R., Goyette, S., and Hyder, S.M., 2016. Luteolin suppresses development of medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumors in Sprague-Dawley rats. Oncology Reports, 35, 825–832.
Fadillah, Y.S., Kurniawan, M.F., and Rohmayanti, T., 2023. Analisis Molecular Docking Senyawa Ekstrak Seledri (Apium Graveolens) Untuk Penghambatan Angiotensin-Converting Enzyme 2. Jurnal Agroindustri Halal, 9 (1), 74–81.
Fauzi, M.F., Wutsqa, Y.U., and Rohmatika, N.A., 2024. Studi Bioavailabilitas Dan Molecular Docking Senyawa Fenolik Ocimum sanctum L. Sebagai Inhibitor Reseptor Estrogen Alfa Pada Sel Kanker Payudara. Akfarindo, 9 (1), 49–56.
Frimayanti, N., Mora, E., and Anugrah, R., 2018. Study of Molecular Docking of Chalcone Analoque Compound as Inhibitors for Liver Cancer Cells HepG2. Computer Engineering and Applications Journal, 7 (2), 137–147.
IARC, 2024. Indonesia Fact Sheet Cancer: Number of New Case in 2022, Female, All ages.
Kemenkes, 2024. Kanker Masih Membebani Dunia [online]. Available from: https://sehatnegeriku.kemkes.go.id/baca/blog/20240506/3045408/kanker-masih-membebani-dunia/ [Accessed 18 Mar 2025].
Kemenkes, 2024. Rencana kanker nasional 2024-2034, (September).
Khairani, S., Keban, S.A., and Afrianty, M., 2019. Evaluation of Drug Side Effects Chemotherapy on Quality of Life (QOL) Breast Cancer Patients at Hospital X in Jakarta. Jurnal Ilmu Kefarmasian Indonesia, 17 (1), 9.
Kollur, S.P., Prasad, S.K., Pradeep, S., Veerapur, R., Patil, S.S., Amachawadi, R.G., S, R.P., Lamraoui, G., Al-Kheraif, A.A., Elgorban, A.M., Syed, A., and Shivamallu, C., 2021. Luteolin-Fabricated ZnO Nanostructures Showed PLK-1 Mediated Anti-Breast Cancer Activity. Biomolecules, 11 (3), 1–21.
Lakhera, S., Rana, M., Devlal, K., Celik, I., and Yadav, R., 2022. A comprehensive exploration of pharmacological properties, bioactivities and inhibitory potentiality of luteolin from Tridax procumbens as anticancer drug by in-silico approach. Structural Chemistry, 33 (3), 703–719.
Listyani, T.A., Addawiyyah, M., and Raharjo, D., 2024. Uji In Silico Toksisitas Senyawa Derivat Flavonoid Beserta Modifikasi Senyawa Baru. Medfarm: Jurnal Farmasi dan Kesehatan, 3 (2), 197–210.
Masand, V.H., Al-Hussain, S.A., Alzahrani, A.Y., Al-Mutairi, A.A., Hussien, R.A., Samad, A., and Zaki, M.E.A., 2024. Estrogen Receptor Alpha Binders for Hormone-Dependent Forms of Breast Cancer: e-QSAR and Molecular Docking Supported by X-ray Resolved Structures. ACS Omega, 9 (14), 16759–16774.
Miziak, P., Baran, M., Błaszczak, E., Przybyszewska-Podstawka, A., Kałafut, J., Smok-Kalwat, J., Dmoszyńska-Graniczka, M., Kiełbus, M., and Stepulak, A., 2023. Estrogen Receptor Signaling in Breast Cancer. Cancers, 15 (19), 1–28.
Noer, S. and Khairullah, M.F., 2023. Studi In-Silico Senyawa Luteolin sebagai Kandidat Obat Antikanker Payudara. Seminar Nasional Sains, 1 (1), 16–22.
Nurhayati, N., Arifin, Z., and Hardono, H., 2019. Kejadian Kanker Payudara (Studi Retrospektif) Di Lampung, Indonesia. Holistik Jurnal Kesehatan, 13 (2), 172–183.
Sahu, A., Ahmad, S., Imtiyaz, K., Kizhakkeppurath Kumaran, A., Islam, M., Raza, K., Easwaran, M., Kurukkan Kunnath, A., Rizvi, M.A., and Verma, S., 2023. In-silico and in-vitro study reveals ziprasidone as a potential aromatase inhibitor against breast carcinoma. Scientific Reports, 13 (16545).
Saleh, B.H.O., 2024. Virtual Screening of Apigenin and Luteolin as Natural Aromatase Inhibitors for the Treatment of Breast Cancer Patients. Iraqi Journal of Industrial Reseach (IJOIR), 11 (2), 129–137.
Siagian, V.H.M., Destia, M., Andini, N.P., and Yustiandini, B.A., 2024. Prediction of Secondary Metabolite Compounds in Lotus (Nelumbo nucifera Gaertn.) Targeting Androgen-α Receptors for Breast Cancer Treatment Using Molecular Docking. Indonesian Journal of Cancer Chemoprevention, 15 (2), 137–149.
Wu, L., Lin, Y., Gao, S., Wang, Y., Pan, H., Wang, Z., Pozzolini, M., Yang, F., Zhang, H., Yang, Y., Xiao, L., and Xu, Y., 2023. Luteolin inhibits triple-negative breast cancer by inducing apoptosis and autophagy through SGK1-FOXO3a-BNIP3 signaling. Frontiers in Pharmacology, 14, 1–14.
