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Recent advances in flavonoid compounds for the treatment of prostate cancer

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Abstract

Prostate cancer is a malignant epithelial tumor of the prostate gland and is the most common malignant tumor of the male genitourinary system. Pharmacological therapies, including chemotherapy and androgen deprivation therapy, play a key role in the treatment of prostate cancer. However, drug resistance and side effects limit the use of these drugs and so there is a need for new drug therapies for prostate cancer patients. Flavonoids, with their wide range of sources and diverse biological activities, have attracted much attention in the field of anti-tumor drug screening. In 2016, at least 58 flavonoids were reported to have anti-prostate cancer activity. In recent years, six additional flavonoid compounds have been found to have anti-prostate cancer potential. In this review, we have collected a large amount of evidence on the anti-prostate cancer effects of these six flavonoids, including a large number of cellular experiments and a small number of preclinical animal experiments. In addition, we predicted their drug-forming properties using Schrödinger’s QikProp software and ADMETlab due to the lack of in vivo pharmacokinetic data for the six compounds. In conclusion, this review has fully confirmed the anti-prostate cancer effects of these six flavonoids, summarized their mechanisms of action and predicted their druggability. It provides a reference for the further development of these compounds into anti-prostate cancer drugs.

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References

  1. Siegel RL, Miller KD, Wagle NS et al (2023) Cancer statistics, 2023. CA Cancer J Clin 73:17–48. https://doi.org/10.3322/caac.21763

    Article  PubMed  Google Scholar 

  2. Pagliuca M, Buonerba C, Fizazi K et al (2019) The evolving systemic treatment landscape for patients with advanced prostate cancer. Drugs 79:381–400. https://doi.org/10.1007/s40265-019-1060-5

    Article  CAS  PubMed  Google Scholar 

  3. Evans AJ (2018) Treatment effects in prostate cancer. Mod Pathol 31:S110-121. https://doi.org/10.1038/modpathol.2017.158

    Article  PubMed  Google Scholar 

  4. Nader R, El Amm J, Aragon-Ching JB (2018) Role of chemotherapy in prostate cancer. Asian J Androl 20:221–229. https://doi.org/10.4103/aja.aja_40_17

    Article  CAS  PubMed  Google Scholar 

  5. Zraik IM, Heß-Busch Y (2021) Management of chemotherapy side effects and their long-term sequelae. Urologe A 60:862–871. https://doi.org/10.1007/s00120-021-01569-7

    Article  PubMed  Google Scholar 

  6. Bilusic M, Madan RA, Gulley JL (2017) Immunotherapy of prostate cancer: facts and hopes. Clin Cancer Res 23:6764–6770. https://doi.org/10.1158/1078-0432.Ccr-17-0019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. De Velasco MA, Uemura H (2018) Prostate cancer immunotherapy: where are we and where are we going? Curr Opin Urol 28:15–24. https://doi.org/10.1097/mou.0000000000000462

    Article  PubMed  Google Scholar 

  8. Gheorghe GS, Hodorogea AS, Ciobanu A et al (2021) Androgen deprivation therapy, hypogonadism and cardiovascular toxicity in men with advanced prostate cancer. Curr Oncol 28:3331–3346. https://doi.org/10.3390/curroncol28050289

    Article  PubMed  PubMed Central  Google Scholar 

  9. Gómez-Aparicio MA, López-Campos F, Pelari-Mici L et al (2022) Bone health and therapeutic agents in advanced prostate cancer. Front Biosci (Landmark Ed) 27:34. https://doi.org/10.31083/j.fbl2701034

    Article  CAS  PubMed  Google Scholar 

  10. Wen K, Fang X, Yang J et al (2021) Recent research on flavonoids and their biomedical applications. Curr Med Chem 28:1042–1066. https://doi.org/10.2174/0929867327666200713184138

    Article  CAS  PubMed  Google Scholar 

  11. Kopustinskiene DM, Jakstas V, Savickas A et al (2020) Flavonoids as anticancer agents. Nutrients. https://doi.org/10.3390/nu12020457

    Article  PubMed  PubMed Central  Google Scholar 

  12. Vue B, Zhang S, Chen QH (2016) Flavonoids with therapeutic potential in prostate cancer. Anticancer Agents Med Chem 16:1205–1229. https://doi.org/10.2174/1871520615666151008122622

    Article  CAS  PubMed  Google Scholar 

  13. Flaig TW, Gustafson DL, Su LJ et al (2007) A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients. Invest New Drugs 25:139–146. https://doi.org/10.1007/s10637-006-9019-2

    Article  CAS  PubMed  Google Scholar 

  14. Flaig TW, Glodé M, Gustafson D et al (2010) A study of high-dose oral silybin-phytosome followed by prostatectomy in patients with localized prostate cancer. Prostate 70:848–855. https://doi.org/10.1002/pros.21118

    Article  CAS  PubMed  Google Scholar 

  15. Nguyen MM, Ahmann FR, Nagle RB et al (2012) Randomized, double-blind, placebo-controlled trial of polyphenon E in prostate cancer patients before prostatectomy: evaluation of potential chemopreventive activities. Cancer Prev Res (Phila) 5:290–298. https://doi.org/10.1158/1940-6207.Capr-11-0306

    Article  CAS  PubMed  Google Scholar 

  16. McLarty J, Bigelow RL, Smith M et al (2009) Tea polyphenols decrease serum levels of prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients and inhibit production of hepatocyte growth factor and vascular endothelial growth factor in vitro. Cancer Prev Res (Phila) 2:673–682. https://doi.org/10.1158/1940-6207.Capr-08-0167

    Article  CAS  PubMed  Google Scholar 

  17. Liu W, Feng Y, Yu S et al (2021) The flavonoid biosynthesis network in plants. Int J Mol Sci. https://doi.org/10.3390/ijms222312824

    Article  PubMed  PubMed Central  Google Scholar 

  18. Varughese RS, Lam WS, Marican A et al (2019) Biopharmacological considerations for accelerating drug development of deguelin, a rotenoid with potent chemotherapeutic and chemopreventive potential. Cancer 125:1789–1798. https://doi.org/10.1002/cncr.32069

    Article  PubMed  Google Scholar 

  19. Zhang P, Zhang M, Mellich TA et al (2022) Variation in rotenone and deguelin contents among strains across four tephrosia species and their activities against aphids and whiteflies. Toxins (Basel). https://doi.org/10.3390/toxins14050339

    Article  PubMed  PubMed Central  Google Scholar 

  20. Thamilselvan V, Menon M, Thamilselvan S (2011) Anticancer efficacy of deguelin in human prostate cancer cells targeting glycogen synthase kinase-3 β/β-catenin pathway. Int J Cancer 129:2916–2927. https://doi.org/10.1002/ijc.25949

    Article  CAS  PubMed  Google Scholar 

  21. Adnan M, Rasul A, Hussain G et al (2020) Ginkgetin: a natural biflavone with versatile pharmacological activities. Food Chem Toxicol 145:111642. https://doi.org/10.1016/j.fct.2020.111642

    Article  CAS  PubMed  Google Scholar 

  22. Jeon YJ, Jung SN, Yun J et al (2015) Ginkgetin inhibits the growth of DU-145 prostate cancer cells through inhibition of signal transducer and activator of transcription 3 activity. Cancer Sci 106:413–420. https://doi.org/10.1111/cas.12608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. You OH, Kim SH, Kim B et al (2013) Ginkgetin induces apoptosis via activation of caspase and inhibition of survival genes in PC-3 prostate cancer cells. Bioorg Med Chem Lett 23:2692–2695. https://doi.org/10.1016/j.bmcl.2013.02.080

    Article  CAS  PubMed  Google Scholar 

  24. Gong G, Guan YY, Zhang ZL et al (2020) Isorhamnetin: a review of pharmacological effects. Biomed Pharmacother 128:110301. https://doi.org/10.1016/j.biopha.2020.110301

    Article  CAS  PubMed  Google Scholar 

  25. Cai F, Zhang Y, Li J et al (2020) Isorhamnetin inhibited the proliferation and metastasis of androgen-independent prostate cancer cells by targeting the mitochondrion-dependent intrinsic apoptotic and PI3K/Akt/mTOR pathway. Biosci Rep. https://doi.org/10.1042/bsr20192826

  26. Ghanbari-Movahed M, Shafiee S, Burcher JT et al (2023) Anticancer potential of apigenin and isovitexin with focus on oncogenic metabolism in cancer stem cells. Metabolites. https://doi.org/10.3390/metabo13030404

    Article  PubMed  PubMed Central  Google Scholar 

  27. He M, Min JW, Kong WL et al (2016) A review on the pharmacological effects of vitexin and isovitexin. Fitoterapia 115:74–85. https://doi.org/10.1016/j.fitote.2016.09.011

    Article  CAS  PubMed  Google Scholar 

  28. Hanafi MMM, Afzan A, Yaakob H et al (2017) In vitro pro-apoptotic and anti-migratory effects of Ficus deltoidea L. plant extracts on the human prostate cancer cell lines PC3. Front Pharmacol 8:895. https://doi.org/10.3389/fphar.2017.00895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Noguchi S, Atsumi H, Iwao Y et al (2016) Nobiletin: a citrus flavonoid displaying potent physiological activity. Acta Crystallogr C Struct Chem 72:124–127. https://doi.org/10.1107/s2053229616000577

    Article  CAS  PubMed  Google Scholar 

  30. Chen J, Creed A, Chen AY et al (2014) Nobiletin suppresses cell viability through AKT pathways in PC-3 and DU-145 prostate cancer cells. BMC Pharmacol Toxicol 15:59. https://doi.org/10.1186/2050-6511-15-59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Deveci Ozkan A, Kaleli S, Onen HI et al (2020) Anti-inflammatory effects of nobiletin on TLR4/TRIF/IRF3 and TLR9/IRF7 signaling pathways in prostate cancer cells. Immunopharmacol Immunotoxicol 42:93–100. https://doi.org/10.1080/08923973.2020.1725040

    Article  CAS  PubMed  Google Scholar 

  32. Liu Y, Yu C, Shao Z et al (2021) Selective degradation of AR-V7 to overcome castration resistance of prostate cancer. Cell Death Dis 12:857. https://doi.org/10.1038/s41419-021-04162-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ozkan AD, Kaleli SM, S, (2021) Evaluation of the effects of nobiletin on toll-like receptor 3 signaling pathways in prostate cancer in vitro. Nutr Cancer 73:1138–1144. https://doi.org/10.1080/01635581.2020.1841247

    Article  CAS  PubMed  Google Scholar 

  34. Ma Y, Ren X, Patel N et al (2020) Nobiletin, a citrus polymethoxyflavone, enhances the effects of bicalutamide on prostate cancer cells via down regulation of NF-κB, STAT3, and ERK activation. RSC Adv 10:10254–10262. https://doi.org/10.1039/c9ra10020b

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Tang M, Ogawa K, Asamoto M et al (2007) Protective effects of citrus nobiletin and auraptene in transgenic rats developing adenocarcinoma of the prostate (TRAP) and human prostate carcinoma cells. Cancer Sci 98:471–477. https://doi.org/10.1111/j.1349-7006.2007.00417.x

    Article  CAS  PubMed  Google Scholar 

  36. Tang MX, Ogawa K, Asamoto M et al (2011) Effects of nobiletin on PhIP-induced prostate and colon carcinogenesis in F344 rats. Nutr Cancer 63:227–233. https://doi.org/10.1080/01635581.2011.523506

    Article  CAS  PubMed  Google Scholar 

  37. Guney Eskiler G, Deveci AO, Bilir C et al (2019) Synergistic effects of nobiletin and sorafenib combination on metastatic prostate cancer cells. Nutr Cancer 71:1299–1312. https://doi.org/10.1080/01635581.2019.1601237

    Article  CAS  PubMed  Google Scholar 

  38. Tuli HS, Rath P, Chauhan A et al (2022) Phloretin, as a potent anticancer compound: from chemistry to cellular interactions. Molecules. https://doi.org/10.3390/molecules27248819

    Article  PubMed  PubMed Central  Google Scholar 

  39. Nakhate KT, Badwaik H, Choudhary R et al (2022) Therapeutic potential and pharmaceutical development of a multitargeted flavonoid phloretin. Nutrients. https://doi.org/10.3390/nu14173638

    Article  PubMed  PubMed Central  Google Scholar 

  40. Gonzalez-Menendez P, Hevia D, Rodriguez-Garcia A et al (2014) Regulation of GLUT transporters by flavonoids in androgen-sensitive and -insensitive prostate cancer cells. Endocrinology 155:3238–3250. https://doi.org/10.1210/en.2014-1260

    Article  CAS  PubMed  Google Scholar 

  41. Kim U, Kim CY, Lee JM et al (2020) Correction to: phloretin inhibits the human prostate cancer cells through the generation of reactive oxygen species. Pathol Oncol Res 26:2011–2012. https://doi.org/10.1007/s12253-019-00667-4

    Article  PubMed  Google Scholar 

  42. Kang D, Zuo W, Wu Q et al (2020) Inhibition of specificity protein 1 is involved in phloretin-induced suppression of prostate cancer. Biomed Res Int 2020:1358674. https://doi.org/10.1155/2020/1358674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Vissenaekens H, Criel H, Grootaert C et al (2022) Flavonoids and cellular stress: a complex interplay affecting human health. Crit Rev Food Sci Nutr 62:8535–8566. https://doi.org/10.1080/10408398.2021.1929822

    Article  PubMed  Google Scholar 

  44. Cui Z, Zhao X, Amevor FK et al (2022) Therapeutic application of quercetin in aging-related diseases: SIRT1 as a potential mechanism. Front Immunol 13:943321. https://doi.org/10.3389/fimmu.2022.943321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Verdoorn BP, Evans TK, Hanson GJ et al (2021) Fisetin for COVID-19 in skilled nursing facilities: senolytic trials in the COVID era. J Am Geriatr Soc 69:3023–3033. https://doi.org/10.1111/jgs.17416

    Article  PubMed  PubMed Central  Google Scholar 

  46. Benavente-García O, Castillo J, Del Baño MJ et al (2001) Improved water solubility of neohesperidin dihydrochalcone in sweetener blends. J Agric Food Chem 49:189–191. https://doi.org/10.1021/jf000186l

    Article  CAS  PubMed  Google Scholar 

  47. Ganesan P, Choi DK (2016) Current application of phytocompound-based nanocosmeceuticals for beauty and skin therapy. Int J Nanomedicine 11:1987–2007. https://doi.org/10.2147/ijn.S104701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Mamouni K, Zhang S, Li X et al (2018) A novel flavonoid composition targets androgen receptor signaling and inhibits prostate cancer growth in preclinical models. Neoplasia 20:789–799. https://doi.org/10.1016/j.neo.2018.06.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Mukhtar E, Adhami VM, Siddiqui IA et al (2016) Fisetin enhances chemotherapeutic effect of cabazitaxel against human prostate cancer cells. Mol Cancer Ther 15:2863–2874. https://doi.org/10.1158/1535-7163.Mct-16-0515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Yang F, Song L, Wang H et al (2015) Combination of quercetin and 2-methoxyestradiol enhances inhibition of human prostate cancer LNCaP and PC-3 cells xenograft tumor growth. PLoS ONE 10:e0128277. https://doi.org/10.1371/journal.pone.0128277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Caminero Gomes Soares A, Marques Sousa GH, Calil RL et al (2023) absorption matters: a closer look at popular oral bioavailability rules for drug approvals. Mol Inform 42:e202300115. https://doi.org/10.1002/minf.202300115

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

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Funding

This research was funded by the Specific Research Project of Guangxi for Research Bases and Talents (AD20159033); and the Initial Scientific Research Fund of Guangxi University of Chinese Medicine (2017BS037).

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Author notes

  1. Wenxuan Fang and Junfang Du have contributed equally to this work.

Authors and Affiliations

  1. Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, 13 Wuhe Road, Qingxiu District, Nanning, 530200, China

    Wenxuan Fang, Mingyi Nie & Xueni Wang

  2. Guangxi Key Laboratory of Marine Drugs, Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning, 530200, China

    Wenxuan Fang & Mingyi Nie

  3. School of Yao Medicine, Guangxi University of Chinese Medicine, 179 Mingxiudong Road, Xixiangtang District, Nanning, 530001, China

    Junfang Du

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  1. Wenxuan Fang
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  4. Xueni Wang
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Contributions

Conceptualization, X.W.; methodology, X.W.; software, X.W.; formal analysis, X.W.; investigation, W.F., J.D. and M.N; resources, X.W. and J.D.; data curation, W.F. and J.D.; writing—original draft preparation, W.F. and J.D.; writing—review and editing, X.W.; visualization, W.F. and X.W.; funding acquisition, J.D. and X.W.

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Correspondence to Xueni Wang.

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Fang, W., Du, J., Nie, M. et al. Recent advances in flavonoid compounds for the treatment of prostate cancer. Mol Biol Rep 51, 653 (2024). https://doi.org/10.1007/s11033-024-09567-6

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