In Vitro Activity Of Apigenin And Luteolin Of Durian Peel (Durio Zibethinus Murray) Induced Apoptosis In Cervical Cancer And Molecular Docking Approach: Involvement Of Bcl-2 Pathways

Ainur Rofiq; M. Dian Islami; Muhammad Zihni Baihaqi; Aditya Sofyansyah Hermaya; Tristan Kanginan; Humaira Medina Liza Lubis

doi:10.55227/ijhet.v5i3.1128

Authors

Ainur Rofiq Universitas Muhammadiyah Sumatera Utara
M. Dian Islami Universitas Muhammadiyah Sumatera Utara
Muhammad Zihni Baihaqi Universitas Muhammadiyah Sumatera Utara
Aditya Sofyansyah Hermaya Universitas Muhammadiyah Sumatera Utara
Tristan Kanginan Universitas Muhammadiyah Sumatera Utara
Humaira Medina Liza Lubis Universitas Muhammadiyah Sumatera Utara

DOI:

https://doi.org/10.55227/ijhet.v5i3.1128

Keywords:

Apigenin, Luteolin, Apoptosis, Cervical Cancer, Durio Zibethinus, Bcl-2

Abstract

Cervical cancer is the fourth most common cancer among women, with resistance to therapy often linked to Bcl-2 overexpression. This study evaluated the anticancer activity of durian peel extract (Durio zibethinus Murray) against HeLa cells through Bcl-2-mediated apoptosis and investigated apigenin and luteolin interactions with Bcl-2 via molecular docking. The extract was prepared by ethanol maceration, characterized by phytochemical screening and GC-MS, and tested for cytotoxicity using the MTT assay, while apoptosis was assessed through Bcl-2 immunofluorescence. Phytochemical screening confirmed flavonoids, alkaloids, saponins, tannins, and triterpenoids, with GC-MS identifying over 93 bioactive compounds. The extract exhibited significant cytotoxicity with an IC₅₀ of 5.92 μg/mL, and cell viability decreased concentration-dependently (p < 0.05), accompanied by apoptotic morphological changes and reduced Bcl-2 expression. Molecular docking revealed favorable binding of apigenin and luteolin to Bcl-2, with binding energies of −6.01 and −5.55 kcal/mol, respectively. In conclusion, durian peel extract demonstrates promising anticancer activity against HeLa cells by inducing apoptosis through Bcl-2 suppression, with apigenin and luteolin serving as potential natural candidates for cervical cancer therapy.

Downloads

Download data is not yet available.

References

Amirulah, F., Annisa, A., Permata, D., & Luthfiana, F. (2026). Efektivitas penggunaan obat antikanker pada pasien kanker serviks di RSUP Fatmawati tahun 2024. 7(1), 187–196.

Boyina, A., Vivek, S., & Shaila, G. (2023). Human papillomavirus infection, cervical cancer and the less explored role of trace elements. Biological Trace Element Research, 201, 1026–1050. https://doi.org/10.1007/s12011-022-03226-2

Chou, B., Venkatesulu, B. P., Coleman, R. L., Harkenrider, M., & Schwarz, J. K. (2022). Management of stage I and II cervical cancer: A review. International Journal of Gynecological Cancer, 32(2), 216–224. https://doi.org/10.1136/ijgc-2021-002527

Ekundina, V. O., & Omon, E. A. (2024). Genomic analysis of BAX and BCL2 gene mutations in human papillomavirus-associated squamous cell carcinoma of the cervix. Surgical and Experimental Pathology, 7, Article 12. https://doi.org/10.1186/s42047-024-00153-5

Ferlay, J., Parkin, D. M., Colombet, M., Soerjomataram, I., Piñeros, M., Znaor, A., & Bray, F. (2021). Cancer statistics for the year 2020: An overview. International Journal of Cancer. https://doi.org/10.1002/ijc.33588

Ferlay, J., Ervik, M., Lam, F., Colombet, M., Mery, L., Piñeros, M., Znaor, A., Soerjomataram, I., & Bray, F. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 74(3), 229–263. https://doi.org/10.3322/CAAC.21834

Fitriatuzzakiyyah, N., Sinuraya, R. K., & Puspitasari, I. M. (2017). Terapi kanker dengan radiasi: Konsep dasar radioterapi dan perkembangannya di Indonesia. Indonesian Journal of Clinical Pharmacy, 6(4), 311–320. https://doi.org/10.15416/ijcp.2017.6.4.311

Khaksar, G., Kasemcholathan, S., & Sirikantaramas, S. (2024). Durian (Durio zibethinus L.): Nutritional composition, pharmacological implications, value-added products, and omics-based investigations. Horticulturae, 10(4), Article 342. https://doi.org/10.3390/horticulturae10040342

Ojha, P. S., Maste, M. M., Tubachi, S., & Patil, V. S. (2022). Human papillomavirus and cervical cancer: An insight highlighting pathogenesis and targeting strategies. Cancer Reports, 33, 132–154.

Prasetyo, E., Kiromah, N. Z. W., & Rahayu, T. P. (2021). Uji aktivitas antioksidan menggunakan metode DPPH (2,2-difenil-1-pikrilhidrazil) terhadap ekstrak etanol kulit buah durian (Durio zibethinus L.) dari Desa Alasmalang Kabupaten Banyumas. Jurnal Pharmascience, 8(1), 75–83. https://doi.org/10.20527/jps.v8i1.9200

Raina, R., Pramodh, S., Rais, N., Haque, S., Shafarin, J., Bajbouj, K., Hamad, M., & Hussain, A. (2021). Luteolin inhibits proliferation, triggers apoptosis and modulates Akt/mTOR and MAP kinase pathways in HeLa cells. Oncology Letters, 21(5). https://doi.org/10.3892/ol.2021.12452

Restaino, S., Pellecchia, G., Arcieri, M., Bogani, G., Taliento, C., Greco, P., Driul, L., Chiantera, V., Ercoli, A., Fanfani, F., Fagotti, A., Ciavattini, A., Scambia, G., Vizzielli, G., & ESGO Group. (2024). Management for cervical cancer patients: A comparison of the guidelines from the international scientific societies. Cancers.

Sains, J., Kes, J. S., Anggraeni, L., Tukan, P., Herawati, F., & Kirtishanti, A. (2024). Resistensi terapi pada kanker serviks: Tinjauan literatur. Jurnal Sains dan Kesehatan, 6(3), 353–360.

Singh, D., Vignat, J., Lorenzoni, V., Eslahi, M., Ginsburg, O., Lauby-Secretan, B., Arbyn, M., Basu, P., Bray, F., & Vaccarella, S. (2023). Global estimates of incidence and mortality of cervical cancer in 2020: A baseline analysis of the WHO Global Cervical Cancer Elimination Initiative. The Lancet Global Health, 11(2), e197–e206. https://doi.org/10.1016/S2214-109X(22)00501-0

Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249. https://doi.org/10.3322/caac.21660

Tarney, C. M., Tian, C., Randall, L. M., Hussain, S. A., Javadian, P., Cronin, S. P., Drayer, S., Chan, J. K., Kapp, D. S., Hamilton, C. A., Leath, C. A., III, Benbrook, D. M., Washington, C. R., Moore, K. N., Bateman, N. W., Conrads, T. P., Phippen, N. T., Maxwell, G. L., & Darcy, K. M. (2025). Long-term survival in patients with low-risk cervical cancer after simple, modified, or radical hysterectomy. JAMA Network Open, 8(5), e2510717. https://doi.org/10.1001/jamanetworkopen.2025.10717

Tuli, H. S., Rath, P., Chauhan, A., Ramniwas, S., & Vashishth, K. (2022). Phloretin as a potent anticancer compound: From chemistry to therapeutic applications. Pharmacological Research, 183, 106402.