Cited by 388Phytochemicals and Antioxidant ActivitiesFlavonoids in Medical ResearchBioactive natural compounds

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The Role of Polyphenol (Flavonoids) Compounds in the Treatment of Cancer Cells

Hazafa, Abu, Rehman, Khalil-Ur-, Jahan, Nazish, Jabeen, Zara·2020·Nutrition and Cancer

DOI 10.1080/01635581.2019.1637006

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Abstract

Cancer remains a second leading cause of deaths and major public health problem. It occurs due to extensive DNA damage caused by ultraviolet radiations, ionizing radiations, environmental agents, therapeutic agents, etc. Among all cancers, the most frequently diagnosed cancers are lung (12.7%), breast (10.9%), colorectal (9.7%), and gastric cancer (7.81%). Natural compounds are most favorable against cancer on the count of their anti-cancerous ability, easy to avail and efficient. Among natural compounds, polyphenols (flavonoids, catechin, hesperetin, flavones, quercetin, phenolic acids, ellagic acid, lignans, stilbenes, etc.) represent a large and diverse group used in the prevention and treatment of cancer. Natural flavonoids are derived from different plant sources and from various medicinal plants including Petroselinum crispum, Apium graveolens, Flemingia vestita, Phyllanthus emblica, etc. Natural flavonoids possess antioxidant, anti-inflammation, as well as anti-cancerous activities through multiple pathways, they induce apoptosis in breast, colorectal, and prostate cancers, lower the nucleoside diphosphate kinase-B activity in lung, bladder and colon cancers, inhibit cell-proliferation and cell cycle arrest by suppressing the NF-kB pathway in various cancers, etc. The current review summarized the anticancer activities of natural polyphenols and their mechanisms of action.

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Tufail, T., Khan, T., Ain, H. B. U., Morya, S., & Shah, M. A. (2024) · Food Science & Nutrition · doi:10.1002/fsn3.4096 · Cited by 31
p-Coumaric acid, Kaempferol, Astragalin and Tiliroside Influence the Expression of Glycoforms in AGS Gastric Cancer Cells
Radziejewska, I., Supruniuk, K., Tomczyk, M., Izdebska, W. M., Borzym‐Κluczyk, M., Bielawska, A., Bielawski, K., & Galicka, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158602 · Cited by 31
“Several other phytochemicals have been proposed to possess capabilities to suppress cancer cell proliferation by blocking NF-κB nuclear translocation or reducing its activation [41,42].”
Background
Flavonoids as promising anticancer agents: anin silicoinvestigation of ADMET, binding affinity by molecular docking and molecular dynamics simulations
Biharee, A., Yadav, A., Jangid, K., Singh, Y., Kulkarni, S., Sawant, D. M., Kumar, P., Thareja, S., & Jain, A. K. (2022) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2022.2126397 · Cited by 31
“, 2020), NFkB/PI3/AkT/ mTOR pathway inhibitors (Hazafa et al., 2020; Jiang et al., 2020; Russo et al., 2017; Zhang et al., 2018), tubulin inhibition (Kaur & Bansal, 2020), and inhibition of ROS production (Kopustinskiene et al.”
Background
An Insight into Anticancer Bioactives from Punica granatum (Pomegranate)
Sharma, K., Kesharwani, P., Prajapati, S. K., Jain, A., Jain, D., Mody, N., & Sharma, S. K. (2021) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520621666210726143553 · Cited by 33
Characterization and optimization of co-delivery Farnesol-Gingerol Niosomal formulation to enhance anticancer activities against breast cancer cells
Lalami, Z. A., Tafvizi, F., Naseh, V., & Salehipour, M. (2022) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2022.103371 · Cited by 30
Apoptotic-Induced Effects of Acacia Catechu Willd. Extract in Human Colon Cancer Cells
Chiaino, E., Micucci, M., Durante, M., Budriesi, R., Gotti, R., Marzetti, C., Chiarini, A., & Frosini, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21062102 · Cited by 29
Antibacterial and antioxidant activity of catechin, gallic acid, and epigallocatechin-3-gallate: focus on nanoformulations
Alavi, M., Hamblin, M. R., Aghaie, E., Mousavi, S. A. R., & Hajimolaali, M. (2023) · Cellular Molecular and Biomedical Reports · doi:10.55705/cmbr.2022.353962.1052 · Cited by 28
Quantitative Analysis of Bioactive Compounds in Commercial Teas: Profiling Catechin Alkaloids, Phenolic Acids, and Flavonols Using Targeted Statistical Approaches
Chen, Y., Lingling, L., You, Y., Gao, R., Xiang, J., Wang, G., & Yu, W. (2023) · Foods · doi:10.3390/foods12163098 · Cited by 28
Genistein: a promising modulator of apoptosis and survival signaling in cancer
Joshi, H., Gupta, D., Abjani, N. K., Kaur, G., Mohan, C. D., Kaur, J., Aggarwal, D., Rani, I., Ramniwas, S., Abdulabbas, H. S., et al. (2023) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-023-02550-1 · Cited by 28
“As the incidence of cancer continues to increase globally, there is a need to explore alternative treatment strategies (Hazafa and Rehman K-U-, Jahan N, Jabeen Z. 2020).”
Background
Discussion on the Structural Modification and Anti-tumor Activity of Flavonoids
Zhou, Z., Li, D., Chen, Y., Chen, X., & Man, R. (2022) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026622666220308162049 · Cited by 27
Therapeutic efficacy of caffeic acid phenethyl ester in cancer therapy: An updated review
Pandey, P., Khan, F., Upadhyay, T. K., & Giri, P. P. (2023) · Chemical Biology & Drug Design · doi:10.1111/cbdd.14233 · Cited by 28
“Flavonoids are natural polyphenolic molecules with multi- beneficial effects, including anticancer, antidiabetic, anti- inflammatory, antiviral, and immunoregulatory activities (Hazafa et al., 2020; Khan et al., 2021; Pandey & Khan, 2021; Vrhovac Madunić et al., 2018; Zhang et al., 2021).”
Background
Effect of quercetin and chrysin and its association on viability and cell cycle progression in MDA-MB-231 and MCF-7 human breast cancer cells
Ramos, P. S., Ferreira, C., Passos, C. L. A., Silva, J. L., & Fialho, E. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117276 · Cited by 26
Obesity and endometrial cancer: biological mechanisms, nutritional strategies, and clinical perspectives
Simancas‐Racines, D., Campuzano-Donoso, M., Román-Galeano, N. M., Zambrano-Villacres, R., Memoli, P., Verde, L., Reytor-González, C., & Carbone, L. (2025) · Food and Agricultural Immunology · doi:10.1080/09540105.2025.2510961 · Cited by 29
“For example, individuals with elevated C-reactive protein (CRP) levels, a marker of chronic inflammation, may benefit from an anti-inflammatory diet emphasising polyphenol-rich foods like berries, green tea, and leafy greens (Hazafa et al., 2020).”
Curcumin promotes apoptosis of human melanoma cells by caspase 3
Manica, D., da Silva, G. B., da Silva, A. P., Marafon, F., Maciel, S. F. V. D. O., Bagatini, M. D., & Moreno, M. (2023) · Cell Biochemistry and Function · doi:10.1002/cbf.3863 · Cited by 26
“10 Among them, curcumin, a polyphenol derived from Curcuma longa , has been considered a pleiotropic molecule since it acts on several molecular targets and is widely explored due to its anti ‐ inflammatory, antioxidant and antineoplastic effects.”
Background
Antioxidant and Antimicrobial Properties of Helichrysum italicum (Roth) G. Don Hydrosol
Bezek, K., Kramberger, K., & Barlič‐Maganja, D. (2022) · Antibiotics · doi:10.3390/antibiotics11081017 · Cited by 29
“Plant natural products exert anti-inflammatory [6], anticarcinogenic [7], anti-diabetic [8], antibacterial, antifungal, antiviral, antimutagenic and antiallergic properties which are often associated with their antioxidant activity [9–11].”
Background
Anthocyanins Reduce Cell Invasion and Migration through Akt/mTOR Downregulation and Apoptosis Activation in Triple-Negative Breast Cancer Cells: A Systematic Review and Meta-Analysis
Rabêlo, A. C. S., Guerreiro, C. D. A., Shinzato, V. I., Ong, T. P., & Noratto, G. D. (2023) · Cancers · doi:10.3390/cancers15082300 · Cited by 27
“Alongside other phenolic compounds, anthocyanins have anticancer chemopreventive effects associated with an increase in apoptosis, a decrease in cell proliferation, as well as cell cycle arrest [8,9].”
Background
Enhancing the Anticancer and Anti-Inflammatory Properties of Curcumin in Combination with Quercetin, for the Prevention and Treatment of Prostate Cancer
PELLEGRINO, M. A., Bevacqua, E., Frattaruolo, L., Cappello, A. R., Aquaro, S., & Tucci, P. (2023) · Biomedicines · doi:10.3390/biomedicines11072023 · Cited by 25
“Among natural compounds, polyphenols represent a large and diverse group that have shown interesting chemopreventive properties without the serious side effects of cytotoxic agents [13].”
Background
Advances in polyphenol-based carbon dots for biomedical engineering applications
Han, J., Hong, J., Lee, H., Choi, S., Shin, K., Gu, M., & Kim, S. (2023) · European Polymer Journal · doi:10.1016/j.eurpolymj.2023.112354 · Cited by 25
Nanocarrier mediated co-delivery of phytochemicals and chemo-drugs: an emerging strategy to combat lung cancer in a systemic way
Upadhyay, P., Ghosh, A., Sarangthem, V., & Singh, T. D. (2023) · Phytochemistry Reviews · doi:10.1007/s11101-023-09894-9 · Cited by 25
“…such as stilbenoids in synergy with resveratrol known for their anticarcinogenic (Alamolhodaei et al. 2017), antioxidant and anti-aging properties (Hazafa et al. 2020 A lately study investigated the long-term, low-dose curcumin effects in NSCLC cells and found signiﬁcant suppression of both the…”
Rosa × damascena Herrm. essential oil: anti-tyrosinase activity and phytochemical composition
Wu, Q., Fang, W., Liu, H., Liu, Z., & Xu, X. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1451452 · Cited by 24
“Essential oils, as important functional metabolites, are usually valued for their antimicrobial and antioxidant properties, often making them as natural preservatives in cosmetic and medicine industries (Hazafa et al., 2020; Carqueijeiro et al., 2020; Li et al., 2020).”
Background
Celery Root Phenols Content, Antioxidant Capacities and Their Correlations after Osmotic Dehydration in Molasses
Nićetin, M. R., Pezo, L. L., Pergal, M. V., Lončar, B. L., Filipović, V., Knežević, V., Demi̇r, H., Filipović, J., & Manojlović, D. (2022) · Foods · doi:10.3390/foods11131945 · Cited by 24
“Many studies have verified that phenolic compounds are involved in preventing cardiovascular, neurodegenerative, and oncological diseases and also exhibit anti-inflammatory and antimicrobial properties [4,5].”
Background
Decanoic Acid Exerts Its Anti-Tumor Effects via Targeting c-Met Signaling Cascades in Hepatocellular Carcinoma Model
Yang, M. H., Lee, M., Deivasigamani, A., Le, D. D., Mohan, C. D., Hui, K. M., Sethi, G., & Ahn, K. S. (2023) · Cancers · doi:10.3390/cancers15194681 · Cited by 24
Anticancer, and antioxidant activities of royal jelly on HT-29 colon cancer cells and melissopalynological analysis
Ayna, A., Tunç, A., ÖZBOLAT, S., Bengü, A. Ş., Aykutoğlu, G., Canlı, D., Polat, R., Çiftçi, M., & Darendelioğlu, E. (2021) · TURKISH JOURNAL OF BOTANY · doi:10.3906/bot-2109-8 · Cited by 23
“Flavonoids also possess anticancer activities (Liu et al., 2010; Zhang et al., 2018; Hazafa et al., 2019) owing to their high antioxidant capacity along with their capability to affect several Abstract: Royal jelly (RJ) is reflecting the flora around the apiaries as a result of the foraging…”
Naringenin as potent anticancer phytocompound in breast carcinoma: from mechanistic approach to nanoformulations based therapeutics
Elsori, D. H., Pandey, P., Ramniwas, S., Kumar, R., Lakhanpal, S., Rab, S. O., Siddiqui, S., Singh, A. V., Saeed, M., & Khan, F. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1406619 · Cited by 24
Sulforaphene inhibits the progression of osteosarcoma via regulating FSTL1/NF-κB pathway
Zhang, G., Jin, C., Zhu, Y., Fu, F., Wang, G., & Li, S. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118485 · Cited by 22
Cell cycle arrest-mediated cell death by morin in MDA-MB-231 triple-negative breast cancer cells
Maharjan, S., Kwon, Y., Lee, M., Lee, K., & Nam, K. (2021) · Pharmacological Reports · doi:10.1007/s43440-021-00272-w · Cited by 22
Flavonoid 4,4′-dimethoxychalcone suppresses cell proliferation via dehydrogenase inhibition and oxidative stress aggravation
Yang, C., Zhu, S., Chen, Y., Liu, Z., Zhang, W., Zhao, C., Luo, C., & Deng, H. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.09.002 · Cited by 22
Modulation of Inflammation by Plant-Derived Nutraceuticals in Tendinitis
Mueller, A., Brockmueller, A., Kunnumakkara, A. B., & Shakibaei, M. (2022) · Nutrients · doi:10.3390/nu14102030 · Cited by 25
Dietary Polyphenol Intake and Gastric Cancer: A Systematic Review and Meta-Analysis
Fagundes, M. D. A., Silva, A. R. C., Fernandes, G. A., & Curado, M. P. (2022) · Cancers · doi:10.3390/cancers14235878 · Cited by 22
“Within natural compounds, polyphenols (including all classes and subclasses) represent a large diverse group used in the prevention and treatment of cancer [39].”
Background
Metabolic profiling and cytotoxic activities of ethanol extract of Dypsis leptocheilos aerial parts and its green synthesized silver nanoparticles supported by network pharmacology analysis
Mohammed, M. H. H., Hamed, A. N. E.-S., Elhabal, S. F., Mokhtar, F. A., Abdelmohsen, U. R., Fouad, M. A., & Kamel, M. S. (2023) · South African Journal of Botany · doi:10.1016/j.sajb.2023.08.026 · Cited by 22
Evaluation of the Antioxidant and Anticancer Activities of Hydroalcoholic Extracts of Thymus daenensis Čelak and Stachys pilifera Benth
Barmoudeh, Z., Ardakani, M. T., Doustimotlagh, A. H., & Bardania, H. (2022) · Journal of Toxicology · doi:10.1155/2022/1924265 · Cited by 21
“,ey can effect on different stages of the onset and growth of cancerous cells [10].”
Background
RETRACTED: Evaluation of the hepatoprotective activity of hydroalcoholic extract of Alhagi camelorum against valproic acid-induced hepatotoxicity in rats
Iqbal, M. O., Manzoor, M., Mumtaz, A., Riaz, R., Arshad, S., Khan, I. A., Javaid, U., Manzoor, Z., Munawar, S. H., Andleeb, S., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112953 · Cited by 21
Retracted
The new exploration of pure total flavonoids extracted from Citrus maxima (Burm.) Merr. as a new therapeutic agent to bring health benefits for people
Ding, S., Wang, P., Pang, X., Zhang, L., Qian, L., Jia, X., Chen, W., Ruan, S., & Sun, L. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.958329 · Cited by 21
Review of dietary patterns and gastric cancer risk: epidemiology and biological evidence
Pu, K., Yang, F., Tang, Q., Yang, G., & Xu, C. S. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1333623 · Cited by 24
ARTIFICIAL INTELLIGENCE, PROBLEMS AND PROSPECTS
Ahmadova, J. M. A. A. A., & Ibrahimov, S. I. S. (2024) · PIRETC-Proceeding of The International Research Education & Training Centre · doi:10.36962/piretc30012024-152 · Cited by 20
Flavonoids and Flavonoid-Based Nanopharmaceuticals as Promising Therapeutic Strategies for Colorectal Cancer—An Updated Literature Review
Smeu, A., Marcovici, I., Dehelean, C. A., Dumitrel, Ș.-I., Borza, C., & Lighezan, R. (2025) · Pharmaceuticals · doi:10.3390/ph18020231 · Cited by 25
“The effects in the oncological area are currently being studied extensively because flavonoids have proven their efficacy against several types of cancers, including colorectal, breast, lung, skin, prostate and bladder cancers [49].”
Flavonoid-Based Combination Therapies and Nano-Formulations: An Emerging Frontier in Breast Cancer Treatment
Uniyal, P., Akhtar, A., & Rawat, R. (2025) · Pharmaceuticals · doi:10.3390/ph18101486 · Cited by 20
“Notably, flavonoids impact cell proliferation via a wide variety of processes, and some of them could interact with numerous cellular components such as intracellular proteins, growth regulators, metal enzymes, transcription genes, and genetic material [7,8].”
Preventive effect of pomegranate juice against chemically induced bladder cancer: An experimental study
Mortada, W. I., Awadalla, A., Khater, S. M., Barakat, N. M., Husseiny, S. M., & Shokeir, A. A. (2020) · Heliyon · doi:10.1016/j.heliyon.2020.e05192 · Cited by 20
“Most of these ingredients, particularly polyphenols and flavonoids, possess anti-cancer properties by cell cycle arrest, inhibition of cellular proliferation and activation of apoptosis (Hazafa et al., 2019).”
Background
Nephroprotective Effects of Alhagi camelorum against Cisplatin-Induced Nephrotoxicity in Albino Wistar Rats
Iqbal, M. O., Ahmed, M. M., Arshad, S., Javaid, U., Khan, I. A., Manzoor, M., Andleeb, S., Riaz, R., Munawar, S. H., Manzoor, Z., et al. (2022) · Molecules · doi:10.3390/molecules27030941 · Cited by 20
Diet and gastric cancer risk: an umbrella review of systematic reviews and meta-analyses of prospective cohort studies
Liu, S., Huang, P.-D., Xu, J., Li, Q., Xie, J., Wu, W.-Z., Wang, C., & Yang, X.-B. (2022) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-022-04005-1 · Cited by 20
“Flavonoids are secondary metabolites of plants, widely found in vegetables, fruits, pasture, and medicinal plants, with antioxidant, antiinflammatory, free radical scavenging, immunomodulatory functions, and also promote the absorption of vitamin C (Hazafa et al. 2020), thus reducing the occurrence of GC.”
Background
Identification of allosteric inhibitor against AKT1 through structure-based virtual screening
Karunakaran, K., & Muniyan, R. (2022) · Molecular Diversity · doi:10.1007/s11030-022-10582-7 · Cited by 21
“Adhesiveness and invasiveness of cancer cells are also reduced thereby diminishing their metastasis [54] Silydianin, abyssinoflavanone VII, 8-C-p-hydroxybenzyldiosmetin, 8-C-p-hydroxyben-zylapigenin, durmillone, dehydodeguelin, lanneaflavonol and 3-prenylbiochanin had better binding affinity and…”
Background
Transcription and Metabolism Pathways of Anthocyanin in Purple Shamrock (Oxalis triangularis A.St.-Hil.)
Luo, B., Chen, L., Chen, G., Wang, Y., Xie, Q., Chen, X., & Hu, Z. (2022) · Metabolites · doi:10.3390/metabo12121290 · Cited by 20
“Furthermore, more and more evidence show that intaking foods rich in anthocyanins can effectively reduce the risk of suffering from obesity [4], cancers [5,6], and cardiovascular disease [7,8].”
Background

Authors: Hazafa, A., Rehman, K.-U., Jahan, N., & Jabeen, Z.
Affiliations: University of Agriculture Faisalabad (PK)
Corresponding author: Hazafa, Abu
ORCID: Hazafa, Abu
Jahan, Nazish
Venue: Nutrition and Cancer
Publisher: Informa UK Limited
Published: 2019-07-09
Volume: 72
Issue: 3
Pages: 386-397
ISSN: 0163-5581 (ISSN-L)
1532-7914
DOI: 10.1080/01635581.2019.1637006
OpenAlex: W2961940793
Cited by: 388
References: 113
Citations by year: 2026: 42 · 2025: 61 · 2024: 99 · 2023: 66 · 2022: 76 · 2021: 29 · 2020: 15
FWCI: 2.89
Type: journal article
Language: en
Open access: closed
Locations: Nutrition and Cancer (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
Health Sciences › Medicine › Pharmacology (medical) › Flavonoids in Medical Research
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Bioactive natural compounds
Keywords: polyphenols, flavonoids, anticancer activity, natural compounds, apoptosis, NF-κB signaling, cell cycle arrest, DNA damage, antioxidant activity, anti-inflammatory activity, quercetin, catechins, ellagic acid, medicinal plants, cancer prevention
MeSH terms: Anthocyanins, Antineoplastic Agents, Antioxidants, Flavonoids, Humans, Neoplasms, Plants, Edible, Plants, Medicinal, Quercetin, Tea, Anticarcinogenic Agents, Apoptosis, Cell Line, Tumor, Cell Proliferation, Polyphenols

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The Role of Polyphenol (Flavonoids) Compounds in the Treatment of Cancer Cells

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