Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Jun 11;42(7):251.
doi: 10.1007/s12032-025-02814-1.

Procyanidins as potential anticancer agents: mechanisms of action, bioavailability challenges and therapeutic opportunities

Adedayo O Ademiluyi  1 , Olubukola H Oyeniran  2 , María Luisa Del Prado-Audelo  3 , Alejandra Romero-Montero  4 , Gerardo Leyva-Gómez  5 , Irene Dini  6 , Solomon Habtemariam  7 , William N Setzer  8   9 , Javad Sharifi-Rad  10   11   12 , Daniela Calina  13
Affiliations
Review

Procyanidins as potential anticancer agents: mechanisms of action, bioavailability challenges and therapeutic opportunities

Adedayo O Ademiluyi et al. Med Oncol. .

Abstract

Procyanidins (PCs), dietary polyphenols found in fruits, vegetables, and beverages, exhibit potent anticancer properties. Their mechanisms of action involve modulating oxidative stress, inhibiting angiogenesis, inducing apoptosis, and preventing tumor progression. Despite promising preclinical and clinical findings, their therapeutic potential remains underexplored. This review aims to provide a comprehensive analysis of the anticancer properties of PCs, including their bioavailability, pharmacokinetics, and safety. A systematic literature search was conducted across databases such as PubMed, Scopus, and Web of Science, utilizing Medical Subject Headings (MeSH) terms and specific keywords. Studies were selected based on predefined inclusion criteria, focusing on in vitro, in vivo, and clinical evidence. PCs demonstrate anticancer effects through multiple pathways, including inhibition of pro-inflammatory cytokines, suppression of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways, and regulation of apoptosis-related proteins such as BCL2-associated X protein (BAX), B-cell lymphoma 2 (BCL-2), and caspases. PCs demonstrate anticancer effects through multiple pathways, including inhibition of pro-inflammatory cytokines, suppression of the PI3K/AKT/mTOR and MAPK/ERK pathways, and regulation of apoptosis-related proteins such as BAX, BCL-2, and caspases. However, their low oral bioavailability and metabolic instability pose challenges for clinical application. Current research highlights the need for novel delivery systems, such as nanoparticles and liposomes, to enhance systemic absorption and therapeutic efficacy. Ongoing clinical trials are investigating the potential of PCs as adjuvants in cancer therapy, either alone or in combination with chemotherapeutic agents. Future studies should focus on optimizing their pharmacokinetics, exploring synergistic effects with existing treatments, and conducting large-scale clinical trials to validate their efficacy and safety. PCs hold promise as natural anticancer agents, with the potential to complement conventional therapies and improve patient outcomes.

Keywords: Antioxidants; Bioavailability; Cancer prevention; Drug resistance; Flavonoids; Metastasis inhibition.

PubMed Disclaimer

Conflict of interest statement

Declarations. Competing interests: The authors wish to confirm that there are no known conflicts of interest associated with this publication, and there has been no significant financial support for this work that could have influenced its outcome. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable.

References

    1. Khurram I, Khan MU, Saleem A, Ibrahim S, Ghani MU, Shahid M, Amin I, Calina D, Sharifi-Rad J. The potential of cell-free DNA in cancer: towards standardization and optimization for enhanced diagnosis and monitoring. J Biol Regul Homeost Agents. 2024;38(4):2713–32. https://doi.org/10.23812/j.biol.regul.homeost.agents.20243804.213 . - DOI
    1. da Cunha AR, Compton K, Xu RX, Mishra R, Drangsholt MT, Antunes JLF, Kerr AR, Acheson AR, Lu D, Wallace LE, Kocarnik JM, Fu WJ, Dean FE, Pennini A, Henrikson HJ, Alam T, Ababneh E, Abd-Elsalam S, Abdoun M, Abidi H, Ali HA, Abu-Gharbieh E, Adane TD, Addo IY, Ahmad A, Ahmad S, Rashid TA, Akonde M, Al Hamad H, Alahdab F, Alimohamadi Y, Alipour V, Al-Maweri SA, Alsharif U, Ansari-Moghaddam A, Anwar SL, Anyasodor AE, Arabloo J, Aravkin AY, Aruleba RT, Asaad M, Ashraf T, Athari SS, Attia S, Azadnajafabad S, Azangou-Khyavy M, Badar M, Baghcheghi N, Banach M, Bardhan M, Barqawi HJ, Bashir NZ, Bashiri A, Benzian H, Bernabe E, Bhagat DS, Bhojaraja VS, Bjorge T, Bouaoud S, Braithwaite D, Briko NI, Calina D, Carreras G, Chakraborty PA, Chattu VK, Chaurasia A, Chen MX, Cho WCS, Chu DT, Chukwu IS, Chung ENC, Cruz-Martins N, Dadras O, Dai XC, Dandona L, Dandona R, Daneshpajouhnejad P, Soltani RDC, Darwesh AM, Debela SA, Molla MD, Dessalegn FN, Dianati-Nasab M, Digesa LE, Dixit SG, Dixit A, Djalalinia S, El Sayed I, El Tantawi M, Enyew DB, Erku DA, Ezzeddini R, Fagbamigbe AF, Falzone L, Fetensa G, Fukumoto T, Gaewkhiew P, Gallus S, Gebrehiwot M, Ghashghaee A, Gill PS, Golechha M, Goleij P, Gomez RS, Gorini G, Guimaraes ALS, Gupta B, Gupta S, Gupta VB, Gupta VK, Haj-Mirzaian A, Halboub ES, Halwani R, Hanif A, Hariyani N, Harorani M, Hasani H, Hassan AM, Hassanipour S, Hassen MB, Hay SI, Hayat K, Herrera-Serna BY, Holla R, Horita N, Hosseinzadeh M, Hussain S, Ilesanmi OS, Ilic IM, Ilic MD, Isola G, Jaiswal A, Jani CT, Javaheri T, Jayarajah U, Jayaram S, Joseph N, Kadashetti V, Kandaswamy E, Karanth SD, Karaye IM, Kauppila JH, Kaur H, Keykhaei M, Khader YS, Khajuria H, Khanali J, Khatib MN, Kashani HRK, Tabari MAK, Kim MS, Kompani F, Koohestani HR, Kumar GA, Kurmi OP, La Vecchia C, Lal DK, Landires I, Lasrado S, Ledda C, Lee YH, Libra M, Lim SS, Listl S, Lopukhov PD, Mafi AR, Mahumud RA, Malik AA, Mathur MR, Maulud SQ, Meena JK, Nasab EM, Mestrovic T, Mirfakhraie R, Misganaw A, Misra S, Mithra P, Mohammad Y, Mohammadi M, Mohammadi E, Mokdad AH, Moni MA, Moraga P, Morrison SD, Mozaffari HR, Mubarik S, Murray CJL, Nair TS, Swamy SN, Narayana AI, Nassereldine H, Natto ZS, Nayak BP, Negru SM, Nggada HA, Nouraei H, Nunez-Samudio V, Oancea B, Olagunju AT, Bali AO, Padron-Monedero A, Padubidri JR, Pandey A, Pardhan S, Patel J, Pezzani R, Piracha ZZ, Rabiee N, Radhakrishnan V, Radhakrishnan RA, Rahmani AM, Rahmanian V, Rao CR, Rao SJ, Rath GK, Rawaf DL, Rawaf S, Rawassizadeh R, Razeghinia MS, Rezaei N, Rezaei N, Rezaei N, Rezapour A, Riad A, Roberts TJ, Romero-Rodriguez E, Roshandel G, Manjula S, Chandan SN, Saddik B, Saeb MR, Saeed U, Safaei M, Sahebazzamani M, Sahebkar A, Farrokhi AS, Samy AM, Santric-Milicevic MM, Sathian B, Satpathy M, Sekerija M, Senthilkumaran S, Seylani A, Shafaat O, Shahsavari HR, Shamsoddin E, Sharew MM, Sharifi-Rad J, Shetty JK, Shivakumar KM, Shobeiri P, Shorofi SA, Shrestha S, Malleshappa SKS, Singh P, Singh JA, Singh G, Sinha DN, Solomon Y, Suleman M, Abdulkader RS, Abkenar YT, Talaat IM, Tan KK, Tbakhi A, Thiyagarajan A, Tiyuri A, Tovani-Palone MR, Unnikrishnan B, Vo B, Volovat SR, Wang C, Westerman R, Wickramasinghe ND, Xiao H, Yu CH, Yuce D, Yunusa I, Zadnik V, Zare I, Zhang ZJ, Zoladl M, Force LM, Hugo FN, Canc GBDLOP. The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories A Systematic Analysis for the Global Burden of Disease Study 2019. JAMA Oncol. 2023;9(10):1401–16. https://doi.org/10.1001/jamaoncol.2023.2960 . - DOI - PubMed - PMC
    1. Santos JV, Padron-Monedero A, Bikbov B, Grad DA, Plass D, Mechili EA, Gazzelloni F, Fischer F, Sulo G, Ngwa CH, Noguer-Zambrano I, Peñalvo JL, Haagsma JA, Kissimova-Skarbek K, Monasta L, Ghith N, Sarmiento-Suarez R, Hrzic R, Haneef R, O’Caoimh R, Cuschieri S, Mondello S, Kabir Z, Freitas A, Devleesschauwer B. The state of health in the European Union (EU-27) in 2019: a systematic analysis for the Global Burden of Disease study 2019. BMC Public Health. 2024;24(1):1374. https://doi.org/10.1186/s12889-024-18529-3 . - DOI - PubMed - PMC
    1. Singh K, Gupta JK, Chanchal DK, Shinde MG, Kumar S, Jain D, Almarhoon ZM, Alshahrani AM, Calina D, Sharifi-Rad J, Tripathi A. Natural products as drug leads: exploring their potential in drug discovery and development. Naunyn-Schmiedebergs Arch Pharmacol. 2024. https://doi.org/10.1007/s00210-024-03622-6 . - DOI - PubMed - PMC
    1. Zlatian OM, Comanescu MV, Rosu AF, Rosu L, Cruce M, Gaman AE, Calina CD, Sfredel V. Histochemical and immunohistochemical evidence of tumor heterogeneity in colorectal cancer. Rom J Morphol Embryol. 2015;56(1):175–81. - PubMed

MeSH terms

LinkOut - more resources