Exploring the Role of Neoflavonoids in Inducing Cell Cycle Arrest in Cancer Cells: In Silico study
Neoflavonoids Inducing Cell Cycle Arrest in Cancer Cells
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Abstract
Background: Cancer remains a major global health problem, with 20 million newly diagnosed cases and an estimated 9.7 million cancer deaths in 2022. Cancer cell proliferation is closely related to the dysregulation of cell cycle progression, which is mainly mediated by cyclin-dependent kinases (CDKs). In this study, neoflavonoids are investigated as novel therapeutic agents that target CDK4, a key regulator of cell cycle transition from G1 to S phase. Method: We performed a pan-cancer analysis of CDK expression using several state-of-the-art databases and found high CDK4 levels in many cancers, and in several cancers higher CDK4 levels were associated with poorer patient survival. Molecular docking studies were performed on 26 neoflavonoid compounds to determine their binding affinity at the ATP binding site of CDK4 to the known inhibitors aemaciclib and flavopiridol. Results: We found that several neoflavonoids bind with similar affinities to these established inhibitors and thus may be effective CDK4 inhibitors. Conclusion: This research shows the therapeutic potential of neoflavonoids in the treatment of cancer and suggests that more preclinical studies are needed to confirm their effectiveness and clarify their mechanisms of action.
References:
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Sedlacek HH. Mechanisms of action of flavopiridol. Crit Rev Oncol Hematol. 2001. 38(2): p. 139-70.
Newcomb EW. Flavopiridol: pleiotropic biological effects enhance its anti-cancer activity. Anticancer Drugs. 2004. 15(5): p. 411-9.
Wang LM,Ren DM. Flavopiridol, the first cyclin-de¬pendent kinase inhibitor: recent advances in com¬bination chemotherapy. Mini Rev Med Chem. 2010. 10(11): p. 1058-70.
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Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P, Franz M, Grouios C, Kazi F, Lopes CT, Maitland A, Mostafavi S, Montojo J, Shao Q, Wright G, Bader GD,Morris Q. The GeneMANIA pre¬diction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 2010. 38(Web Server issue): p. W214-20.
Liu Y, Yang X, Gan J, Chen S, Xiao ZX,Cao Y. CB-Dock2: improved protein-ligand blind docking by in¬tegrating cavity detection, docking and homologous template fitting. Nucleic Acids Res. 2022. 50(W1): p. W159-w164.
Mathesius U, Flavonoid functions in plants and their interactions with other organisms. 2018, MDPI. p. 30.
Havsteen B. Flavonoids, a class of natural products of high pharmacological potency. Biochemical pharma-cology. 1983. 32(7): p. 1141-1148.
El Hachem G, Gombos A,Awada A. Abemaciclib, a third CDK 4/6 inhibitor for the treatment of hormone receptor-positive, human epidermal growth factor re¬ceptor 2-negative advanced or metastatic breast can¬cer. Expert Rev Anticancer Ther. 2021. 21(1): p. 81-92.
Yang L, Chen Y, Wang N,Han W. A narrative review of the clinical development of CDK4/6 inhibitor abe-maciclib in
Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I,Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mor¬tality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024. 74(3): p. 229-263.
Liu B, Zhou H, Tan L, Siu KTH,Guan X-Y. Exploring treatment options in cancer: tumor treatment strat¬egies. Signal Transduction and Targeted Therapy. 2024. 9(1): p. 175.
Debela DT, Muzazu SG, Heraro KD, Ndalama MT, Mesele BW, Haile DC, Kitui SK,Manyazewal T. New approaches and procedures for cancer treatment: Current perspectives. SAGE Open Med. 2021. 9: p. 20503121211034366.
Malumbres M. Cyclin-dependent kinases. Genome Biology. 2014. 15(6): p. 122.
Ding L, Cao J, Lin W, Chen H, Xiong X, Ao H, Yu M, Lin J,Cui Q. The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer. Int J Mol Sci. 2020. 21(6).
Guan L, Tang Y, Li G, Qin Z,Li S. Comprehensive Analysis of Role of Cyclin-Dependent Kinases Fami¬ly Members in Colorectal Cancer. Frontiers in Oncol¬ogy. 2022. 12.
Lotfi MS,Kalalinia F. Flavonoids in Combination with Stem Cells for the Treatment of Neurological Disorders. Neurochem Res. 2023. 48(11): p. 3270- 3282.
Lotfi MS,Rassouli FB. Natural Flavonoid Apigenin, an Effective Agent Against Nervous System Cancers. Mol Neurobiol. 2024. 61(8): p. 5572-5583.
Sedlacek HH. Mechanisms of action of flavopiridol. Crit Rev Oncol Hematol. 2001. 38(2): p. 139-70.
Newcomb EW. Flavopiridol: pleiotropic biological effects enhance its anti-cancer activity. Anticancer Drugs. 2004. 15(5): p. 411-9.
Wang LM,Ren DM. Flavopiridol, the first cyclin-de¬pendent kinase inhibitor: recent advances in com¬bination chemotherapy. Mini Rev Med Chem. 2010. 10(11): p. 1058-70.
Zhai S, Senderowicz AM, Sausville EA,Figg WD. Flavopiridol, a novel cyclin-dependent kinase in¬hibitor, in clinical development. Ann Pharmacother. 2002. 36(5): p. 905-11.
Zhang M, Zhang L, Hei R, Li X, Cai H, Wu X, Zheng Q,Cai C. CDK inhibitors in cancer therapy, an over¬view of recent development. Am J Cancer Res. 2021. 11(5): p. 1913-1935.
Tang Z, Li C, Kang B, Gao G, Li C,Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Re¬search. 2017. 45(W1): p. W98-W102.
Chandrashekar DS, Karthikeyan SK, Korla PK, Patel H, Shovon AR, Athar M, Netto GJ, Qin ZS, Kumar S, Manne U, Creighton CJ,Varambally S. UALCAN: An update to the integrated cancer data analysis plat¬form. Neoplasia. 2022. 25: p. 18-27.
Li T, Fan J, Wang B, Traugh N, Chen Q, Liu JS, Li B,Liu XS. TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells. Can¬cer Res. 2017. 77(21): p. e108-e110.
Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P, Franz M, Grouios C, Kazi F, Lopes CT, Maitland A, Mostafavi S, Montojo J, Shao Q, Wright G, Bader GD,Morris Q. The GeneMANIA pre¬diction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 2010. 38(Web Server issue): p. W214-20.
Liu Y, Yang X, Gan J, Chen S, Xiao ZX,Cao Y. CB-Dock2: improved protein-ligand blind docking by in¬tegrating cavity detection, docking and homologous template fitting. Nucleic Acids Res. 2022. 50(W1): p. W159-w164.
Mathesius U, Flavonoid functions in plants and their interactions with other organisms. 2018, MDPI. p. 30.
Havsteen B. Flavonoids, a class of natural products of high pharmacological potency. Biochemical pharma-cology. 1983. 32(7): p. 1141-1148.
El Hachem G, Gombos A,Awada A. Abemaciclib, a third CDK 4/6 inhibitor for the treatment of hormone receptor-positive, human epidermal growth factor re¬ceptor 2-negative advanced or metastatic breast can¬cer. Expert Rev Anticancer Ther. 2021. 21(1): p. 81-92.
Yang L, Chen Y, Wang N,Han W. A narrative review of the clinical development of CDK4/6 inhibitor abe-maciclib in
| Files | ||
| Issue | Vol 17 No 2 (2025) | |
| Section | Original Articles | |
| Keywords | ||
| Flavopiridol Cancer therapy CDK4 Pan-Cancer | ||
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How to Cite
1.
Jafari-Sabet M, Lotfi M-S. Exploring the Role of Neoflavonoids in Inducing Cell Cycle Arrest in Cancer Cells: In Silico study. Basic Clin Cancer Res. 2026;17(2).
