Prediction of Kaempferol from Kersen Leaf (Muntingia calabura L.) as THIF1A Expression Inhibitor for Glioblastoma

Ratna Mildawati; Yuneka  Saristiana; Fendy Prasetyawan; Muhammad Nurul  Fadel; Emma Jayanti  Besan

Authors

Ratna Mildawati STIKes Ganesha Husada Kediri Author
Yuneka Saristiana Universitas Kadiri Author https://orcid.org/0000-0001-6912-3285
Fendy Prasetyawan Universitas Kadiri Author https://orcid.org/0000-0002-5931-6734
Muhammad Nurul Fadel Universitas Muhammadiyah Kudus Author https://orcid.org/0000-0001-8515-6167
Emma Jayanti Besan Universitas Muhammadiyah Kudus Author https://orcid.org/0000-0002-6381-7515

Keywords:

Kaempferol, Muntingia calabura L., HIF-1α, glioblastoma

Abstract

This study explores the potential of kaempferol, a compound derived from Muntingia calabura L., as an effective inhibitor of HIF-1α expression, a key factor in glioblastoma progression. Computational predictions using the PASS Online platform reveal a high probability of kaempferol’s activity (Pa = 0.969) and an extremely low probability of inactivity (Pi = 0.002), indicating its strong potential to inhibit HIF-1α. Since HIF-1α is critical in tumor cell proliferation, angiogenesis, and resistance to therapies, targeting this pathway could offer a promising therapeutic strategy for glioblastoma treatment. In addition, kaempferol's established pharmacological properties, including antioxidant, anti-inflammatory, and anticancer effects, further highlight its therapeutic potential. By inhibiting HIF-1α, kaempferol may also suppress VEGF-mediated angiogenesis, thus contributing to the inhibition of tumor growth and progression. This study supports the notion that kaempferol, through its ability to target critical signaling pathways involved in glioblastoma, may serve as a valuable natural agent for cancer therapy.

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References

Calderón-Montaño, J. M., Burgos-Morón, E., Pérez-Guerrero, C., & López-Lázaro, M. (2011). A review on the dietary flavonoid kaempferol. Mini Reviews in Medicinal Chemistry, 11(4), 298-344.

Chen, A. Y., & Chen, Y. C. (2013). A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention. Food Chemistry, 138(4), 2099-2107.

Cragg, G. M., & Newman, D. J. (2005). Plants as a source of anti-cancer agents. Journal of Ethnopharmacology, 100(1-2), 72-79.

Ekins, S., Mestres, J., & Testa, B. (2007). In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling. British Journal of Pharmacology, 152(1), 9-20.

Holland, E. C. (2000). Glioblastoma multiforme: the terminator. Proceedings of the National Academy of Sciences, 97(12), 6242-6244.

Imran, M., Rauf, A., Shah, Z. A., Saeed, F., Imran, A., Arshad, M. U., ... & Mubarak, M. S. (2019). Chemo-preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review. Phytotherapy Research, 33(2), 263-275.

Kitchen, D. B., Decornez, H., Furr, J. R., & Bajorath, J. (2004). Docking and scoring in virtual screening for drug discovery: methods and applications. Nature Reviews Drug Discovery, 3(11), 935-949.

Li, Z., Bao, S., Wu, Q., Wang, H., Eyler, C., Sathornsumetee, S., ... & Rich, J. N. (2009). Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell, 15(6), 501-513.

Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., & Olson, A. J. (2009). AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of Computational Chemistry, 30(16), 2785-2791.

Ostrom, Q. T., Gittleman, H., Liao, P., Rouse, C., Chen, Y., Dowling, J., ... & Barnholtz-Sloan, J. S. (2014). CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007–2011. Neuro-oncology, 16(suppl_4), iv1-iv63.

Semenza, G. L. (2003). Targeting HIF-1 for cancer therapy. Nature Reviews Cancer, 3(10), 721-732.

Semenza, G. L. (2012). Hypoxia-inducible factors in physiology and medicine. Cell, 148(3), 399-408.

Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J., ... & Mirimanoff, R. O. (2005). Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New England Journal of Medicine, 352(10), 987-996.

Wang, J., Zhang, Y., Yuan, Y., Xu, Y., & Shen, J. (2015). Kaempferol inhibits cell growth and progression of human glioma cells through downregulation of microRNA-21. Neurochemical Research, 40(3), 525-533.

Yoshida, M., Sakai, T., Hosokawa, N., Marui, N., Matsumoto, K., Fujioka, A., ... & Nishino, H. (1990). The effect of quercetin on cell cycle progression and growth of human gastric cancer cells. FEBS Letters, 260(1), 10-13.

Zagzag, D., Zhong, H., Scalzitti, J. M., Laughner, E., Simons, J. W., & Semenza, G. L. (2000). Expression of hypoxia-inducible factor 1α in brain tumors: association with angiogenesis, invasion, and progression. Cancer, 88(11), 2606-2618.

Zhang, Y., Chen, A. Y., Li, M., Chen, C., Yao, Q., & Ginkgo, B. (2008). Kaempferol inhibits VEGF expression in ovarian cancer cells. International Journal of Molecular Sciences, 9(5), 562-573.