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Dergiler / European Journal of Biology / 2026 / Volume: 85 Issue: 1

Impacts of Phenolic Compounds Alone and in Combination with Natural Substances or Drugs on Cancer Cells

Burhan Budak(HATAY MUSTAFA KEMAL UNIVERSITY)0000-0002-3715-5861
Sevim Beyza Öztürk Sarıkaya(GUMUSHANE UNIVERSITY)0000-0002-7820-4260
Sayfa
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Yayın Tarihi
2026-02-26
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⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

Consequently, they highlight the therapeutic potential of PCs as complementary agents in cancer treatment strategies.

📌 3 Maddede Bu Makale

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Amaç & Hipotez:Phenolic compounds (PCs) are secondary metabolites found in the root and flower parts of plants that help protect the plant from pathogens.
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Temel Bulgular & Veri:Although many chemotherapeutic drugs are used against cancer, the tendency to use other drugs or other applications has increased because the effectiveness of chemotherapeutic drugs is low and healthy cells are damaged in the process.
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Sonuç & Katkı:Consequently, they highlight the therapeutic potential of PCs as complementary agents in cancer treatment strategies.
🔬Tür:Literatür & Derleme Çalışması
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Phenolic compounds · Cancer · Antioxidant

Abstract

Phenolic compounds (PCs) are secondary metabolites found in the root and flower parts of plants that help protect the plant from pathogens. The amount and content of the plant species and the environment in which they live vary. Because PCs have antioxidant properties, they have a preventive effect against oxidising substances. Therefore, PCs in the human diet contribute to the prevention of cancer, osteoporosis, diabetes, and many other diseases. Cancer is the most dangerous and deadly disease among these diseases today. Although many chemotherapeutic drugs are used against cancer, the tendency to use other drugs or other applications has increased because the effectiveness of chemotherapeutic drugs is low and healthy cells are damaged in the process. PCs boost the effectiveness of chemotherapeutic drugs against cancer cells while, preserving the health of other cells. In this review, and studies conducted in cancer lines, applications of PCs alone, combined applications of PCs with natural substances, and the effects of PCs with drugs were investigated and discussed. In conclusion, gallic acid, ellagic acid, caffeic acid, and ferulic acid are frequently used in cancer treatment. These findings highlight the potential of PCs as versatile adjuvants in cancer treatment, which can increase drug efficacy, protect healthy cells, and minimise toxicity. Consequently, they highlight the therapeutic potential of PCs as complementary agents in cancer treatment strategies.

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Bu Makaleye Atıf Yap

Budak, B., Sarıkaya, S. B. Ö. (2026). Impacts of Phenolic Compounds Alone and in Combination with Natural Substances or Drugs on Cancer Cells. European Journal of Biology, Volume: 85 Issue: 1. https://doi.org/10.26650/EurJBiol.2026.1775308

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Kaynakça (70)

  1. Alara OR, Abdurahman NH, Ukaegbu CI. Extraction of phenolic compounds: A review. Curr Res Food Sci. 2021;4:200-214. doi:10.1016/j.crfs.2021.03.011 google scholar
  2. Heleno SA, Martins A, Queiroz MJRP, Ferreira ICFR. Bioactivity of phenolic acids: Metabolites versus parent compounds: A review. Food Chem. 2015;173:501-513. doi:10.1016/j.foodchem.2014.10.0 google scholar
  3. Albuquerque BR, Heleno SA, Oliveira MBPP, Barros L, Ferreira ICFR. Phenolic compounds: Current industrial applications, limitations and future challenges. Food Funct. 2021;12(1):14-29. doi:10.1039/D0FO0232 google scholar
  4. Cianciosi D, Forbes-Hernández TY, Afrin S, et al. Phenolic compounds in honey and their associated health benefits: A review. Molecules. 2018;23(9):2322. doi:10.3390/molecules230923 google scholar
  5. Nićiforović N, Abramovič H. Sinapic acid and its derivatives: Natural sources and bioactivity. Compr Rev Food Sci Food Saf. 2014;13(1):34-51. doi:10.1111/1541-4337.120 google scholar
  6. Alfei S, Marengo B, Zuccari G. Oxidative Stress, antioxidant capabilities, and bioavailability: Ellagic acid or urolithins? Antioxidants. 2020;9(8):707. doi:10.3390/antiox90807 google scholar
  7. Alam W, Khan H, Shah MA, Cauli O, Saso L. Kaempferol as a dietary anti- inflammatory agent: Current therapeutic standing. Molecules. 2020;25(18):4073. doi:10.3390/molecules251840 google scholar
  8. Rauf A, Imran M, Khan IA, et al. Anticancer potential of quercetin: A comprehensive review. Phyther Res. 2018;32(11):2109-2130. doi:10.1002/ptr.61 google scholar
  9. Gao Y, Snyder SA, Smith JN, Chen YC. Anticancer properties of baicalein: A review. Med Chem Res. 2016;25(8):1515-1523. doi:10.1007/s00044-016-1607 google scholar
  10. Hung WL, Chang WS, Lu WC, et al. Pharmacokinetics, bioavailability, tissue distribution and excretion of tangeretin in rat. J Food Drug Anal. 2018;26(2):849-857. doi:10.1016/j.jfda.2017.08.0 google scholar
  11. Imran M, Rauf A, Abu-Izneid T, et al. Luteolin, a flavonoid, as an anticancer agent: A review. Biomed Pharmacother. 2019;112:108612. doi:10.1016/j.biopha.2019.1086 google scholar
  12. Salehi B, Venditti A, Sharifi-Rad M, et al. The therapeutic potential of apigenin. Int J Mol Sci. 2019;20(6):1305. doi:10.3390/ijms200613 google scholar
  13. Isemura M. Catechin in human health and disease. Molecules. 2019;24(3):528. doi:10.3390/molecules240305 google scholar
  14. Ahmed S, Khan H, Aschner M, Hasan MM, Hassan STS. Therapeutic potential of naringin in neurological disorders. Food Chem Toxicol. 2019;132:110646. doi:10.1016/j.fct.2019.1106 google scholar
  15. Chen HJ, Chung YL, Li CY, et al. Taxifolin resensitizes multidrug resistance cancer cells via uncompetitive ınhibition of p-glycoprotein function. Molecules. 2018;23(12):3055. doi:10.3390/molecules231230 google scholar
  16. Xiong H, Wang J, Ran Q, et al. Hesperidin: A therapeutic agent for obesity. Drug Des Devel Ther. 2019;13:3855-3866. doi:10.2147/DDDT.S2274 google scholar
  17. Durazzo A, Lucarini M, Souto EB, et al. Polyphenols: A concise overview on the chemistry, occurrence, and human health. Phyther Res. 2019;33(9):2221-2243. doi:10.1002/ptr.64 google scholar
  18. Farha AK, Yang QQ, Kim G, et al. Tannins as an alternative to antibiotics. Food Biosci. 2020;38:100751. doi:10.1016/j.fbio.2020.1007 google scholar
  19. Kopustinskiene DM, Jakstas V, Savickas A, Bernatoniene J. Flavonoids as anticancer agents. Nutrients. 2020;12(2):457. doi:10.3390/nu120204 google scholar
  20. Costea T, Vlad OC, Miclea LC, Ganea C, Szöllősi J, Mocanu MM. Alleviation of multidrug resistance by flavonoid and non-flavonoid compounds in breast, lung, colorectal and prostate cancer. Int J Mol Sci. 2020;21(2):401. doi:10.3390/ijms210204 google scholar
  21. Soleymani S, Habtemariam S, Rahimi R, Nabavi SM. The what and who of dietary lignans in human health: Special focus on prooxidant and antioxidant effects. Trends Food Sci Technol. 2020;106:382-390. doi:10.1016/j.tifs.2020.10.0 google scholar
  22. El Khawand T, Courtois A, Valls J, Richard T, Krisa S. A review of dietary stilbenes: Sources and bioavailability. Phytochem Rev. 2018;17(5):1007-1029. doi:10.1007/s11101-018-9578 google scholar
  23. Dai J, Mumper RJ. Plant phenolics: Extraction, analysis and their antioxidant and anticancer properties. Molecules. 2010;15(10):7313-7352. doi:10.3390/molecules151073 google scholar
  24. Mutha RE, Tatiya AU, Surana SJ. Flavonoids as natural phenolic compounds and their role in therapeutics: An overview. Futur J Pharm Sci. 2021;7(1):25. doi:10.1186/s43094-020-00161 google scholar
  25. García-Lafuente A, Guillamón E, Villares A, Rostagno MA, Martínez JA. Flavonoids as anti-inflammatory agents: Implications in cancer and cardiovascular disease. Inflamm Res. 2009;58(9):537-552. doi:10.1007/s00011-009-0037 google scholar
  26. Ko EB, Jang YG, Kim CW, Go RE, Lee HK, Choi KC. Gallic acid hindered lung cancer progression by ınducing cell cycle arrest and apoptosis in A549 lung cancer cells via PI3K/Akt pathway. Biomol Ther (Seoul). 2022;30(2):151-161. doi:10.4062/biomolther.2021.0 google scholar
  27. Fu YK, Wang BJ, Tseng JC, et al. Combination treatment of docetaxel with caffeic acid phenethyl ester suppresses the survival and the proliferation of docetaxel-resistant prostate cancer cells via induction of apoptosis and metabolism interference. J Biomed Sci. 2022;29(1):16. doi:10.1186/s12929-022-00797 google scholar
  28. Hong R, Lim SC, Lee TB, Han SI. Anticancer Effect of gallic acid on acidity- induced invasion of MCF7 breast cancer cells. Nutrients. 2023;15(16):3596. doi:10.3390/nu151635 google scholar
  29. Tan Z, Li X, Chen X, et al. Ellagic acid inhibits tumor growth and potentiates the therapeutic efficacy of sorafenib in hepatocellular carcinoma. Heliyon. 2024;10(1):e23931. doi:10.1016/j.heliyon.2023.e239 google scholar
  30. He H, Li B, Rankin GO, Rojanasakul Y, Chen YC. Selecting bioactive phenolic compounds as potential agents to inhibit proliferation and VEGF expression in human ovarian cancer cells. Oncol Lett. 2015;9(3):1444-1450. doi:10.3892/ol.2014.28 google scholar
  31. Su P, Veeraraghavan VP, Krishna Mohan S, Lu W. A ginger derivative, zingerone—a phenolic compound—induces ROS‐mediated apoptosis in colon cancer cells (HCT‐116). J Biochem Mol Toxicol. 2019;33(12):e22403. doi:10.1002/jbt.224 google scholar
  32. Mohammed Saleem Y, Selim M. MDM2 as a target for ellagic acid‑mediated suppression of prostate cancer cells in vitro. Oncol Rep. 2020;44(3):1255-1265. doi:10.3892/or.2020.76
  33. Jang YG, Ko EB, Choi KC. Gallic acid, a phenolic acid, hinders the progression of prostate cancer by inhibition of histone deacetylase 1 and 2 expression. J Nutr Biochem. 2020;84:108444. doi:10.1016/j.jnutbio.2020.1084
  34. Panneerselvam C, Alalawy AI, Albalawi K, et al. Anticancer activity of bioactive compound chavicol as potential toxic against human lung cancer A549 cells. J Drug Deliv Sci Technol. 2022;73:103442. doi:10.1016/j.jddst.2022.1034
  35. Assumpção JHM, Takeda AAS, Sforcin JM, Rainho CA. Effects of propolis and phenolic acids on triple-negative breast cancer cell lines: Potential involvement of epigenetic mechanisms. Molecules. 2020;25(6):1289. doi:10.3390/molecules250612
  36. Wang N, Wang ZY, Mo SL, et al. Ellagic acid, a phenolic compound, exerts antiangiogenesis effects via VEGFR-2 signaling pathway in breast cancer. Breast Cancer Res Treat. 2012;134(3):943-955. doi:10.1007/s10549-012-1977
  37. Bai X, Lai T, Zhou T, Li Y, Li X, Zhang H. In vitro antioxidant activities of phenols and oleanolic acid from mango peel and their cytotoxic effect on A549 cell line. Molecules. 2018;23(6):1395. doi:10.3390/molecules230613
  38. Chen W, Shen X, Ma L, et al. Phenolic compounds from Polygonum chinense induce growth ınhibition and apoptosis of cervical cancer SiHa cells. Biomed Res Int. 2020;2020(1).:8868508. doi:10.1155/2020/88685
  39. Saenglee S, Jogloy S, Patanothai A, Leid M, Senawong T. Cytotoxic effects of peanut phenolics possessing histone deacetylase inhibitory activity in breast and cervical cancer cell lines. Pharmacol Rep. 2016;68(6):1102-1110. doi:10.1016/ j.pharep.2016.06.0
  40. Khorsandi K, Chamani E, Hosseinzadeh G, Hosseinzadeh R. Comparative study of photodynamic activity of methylene blue in the presence of salicylic acid and curcumin phenolic compounds on human breast cancer. Lasers Med Sci. 2019;34(2):239-246. doi:10.1007/s10103-018-2571
  41. Bedolla N, Wu H, Liı L, Liu X, Ren Y. Gallic acid suppresses esophageal squamous cell carcinoma progression and enhances cisplatin chemosensitivity through IL-6/STAT3/Notch pathway. Oncol Res. 2025;33(6):1473-1484. doi:10.32604/ or.2025.0601
  42. Villota H, Moreno-Ceballos M, Santa-González GA, et al. Biological impact of phenolic compounds from coffee on colorectal cancer. Pharmaceuticals. 2021;14(8):761. doi:10.3390/ph140807
  43. Dodurga Y, Vural H, Kurar E, Eroglu C, Avci E, Secme M. The combination effect of ferulic acid and gemcitabine on expression of genes related apoptosis and metastasis in PC-3 prostate cancer cells. Eur J Biol. 2019;77(1):32-37. doi:10.26650/ EuroJBiol.2018.00
  44. Dian C, Qian Z, Ran M, Yan X, Dian L. Co-delivery of docetaxel and curcumin functionalized mixed micelles for the treatment of drug-resistant breast cancer by oral administration. Int J Nanomed. 2024;19:8603-8620. doi:10.2147/IJN.S4724
  45. Zhu X, Yu Z, Feng L, et al. Chitosan-based nanoparticle co-delivery of docetaxel and curcumin ameliorates anti-tumor chemoimmunotherapy in lung cancer. Carbohydr Polym. 2021;268:118237. doi:10.1016/j.carbpol.2021.1182
  46. Tolba MF, Esmat A, Al‐Abd AM, et al. Caffeic acid phenethyl ester synergistically enhances docetaxel and paclitaxel cytotoxicity in prostate cancer cells. IUBMB Life. 2013;65(8):716-729. doi:10.1002/iub.11
  47. Suberu JO, Romero‐Canelón I, Sullivan N, Lapkin AA, Barker GC. Comparative cytotoxicity of artemisinin and cisplatin and their ınteractions with chlorogenic acids in MCF7 breast cancer cells. ChemMedChem. 2014;9(12):2791-2797. doi:10.1002/cmdc.2014022
  48. Liao X, Gao Y, Sun L, et al. Rosmarinic acid reverses non‐small cell lung cancer cisplatin resistance by activating the MAPK signaling pathway. Phyther Res. 2020;34(5):1142-1153. doi:10.1002/ptr.65
  49. Park WH, Kim SH. MAPK inhibitors augment gallic acid-induced A549 lung cancer cell death through the enhancement of glutathione depletion. Oncol Rep. 2013;30(1):513-519. doi:10.3892/or.2013.24
  50. Huang WC. Abstract 2001: Caffeic acid phenethyl ester inhibits growth of human lung adenocarcinoma cells with an epidermal growth factor receptor T790M mutation susceptible property. Cancer Res. 2012;72(8_Supplement):2001-2001. doi:10.1158/1538-7445.AM2012-20
  51. Murtaza G, Sajjad A, Mehmood Z, Shah SH, Siddiqi AR. Possible molecular targets for therapeutic applications of caffeic acid phenethyl ester in inflammation and cancer. J Food Drug Anal. 2015;23(1):11-18. doi:10.1016/ j.jfda.2014.06.0
  52. Yousuf M, Shamsi A, Khan P, et al. Ellagic acid controls cell proliferation and induces apoptosis in breast cancer cells via inhibition of cyclin-dependent kinase 6. Int J Mol Sci. 2020;21(10):3526. doi:10.3390/ijms211035
  53. Kabała-Dzik A, Rzepecka-Stojko A, Kubina R, et al. Comparison of two components of propolis: Caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) induce apoptosis and cell cycle arrest of breast cancer cells MDAMB-231. Molecules. 2017;22(9):1554. doi:10.3390/molecules220915
  54. Sales MS, Roy A, Antony L, Banu SK, Jeyaraman S, Manikkam R. Octyl gallate and gallic acid isolated from Terminalia bellarica regulates normal cell cycle in human breast cancer cell lines. Biomed Pharmacother. 2018;103:1577-1584. doi:10.1016/j.biopha.2018.04.1
  55. Hanieh H, Ibrahim HIM, Mohammed M, Alwassil OI, Abukhalil MH, Farhan M. Activation of aryl hydrocarbon receptor signaling by gallic acid suppresses progression of human breast cancer in vitro and in vivo. Phytomedicine. 2022;96:153817. doi:10.1016/j.phymed.2021.1538
  56. Chen H, Guan Y, Baek SJ, Zhong Q. Caffeic Acid phenethyl ester loaded in microemulsions: Enhanced in vitro activity against colon and breast cancer cells and possible cellular mechanisms. Food Biophys. 2019;14(1):80-89. doi:10.1007/s11483-018-9559
  57. Wang K, Zhu X, Zhang K, Zhu L, Zhou F. Investigation of gallic acid induced anticancer effect in human breast carcinoma MCF‐7 cells. J Biochem Mol Toxicol. 2014;28(9):387-393. doi:10.1002/jbt.215
  58. Kaur H, Ghosh S, Kumar P, Basu B, Nagpal K. Ellagic acid-loaded, tween 80coated, chitosan nanoparticles as a promising therapeutic approach against breast cancer: In vitro and in vivo study. Life Sci. 2021;284:119927. doi:10.1016/ j.lfs.2021.1199
  59. Ali OM, Bekhit AA, Khattab SN, et al. Synthesis of lactoferrin mesoporous silica nanoparticles for pemetrexed/ellagic acid synergistic breast cancer therapy. Colloids Surfaces B Biointerfaces. 2020;188:110824. doi:10.1016/ j.colsurfb.2020.1108
  60. Karthikeyan S, Kanimozhi G, Prasad NR, Mahalakshmi R. Radiosensitizing effect of ferulic acid on human cervical carcinoma cells in vitro. Toxicol in Vitr. 2011;25(7):1366-1375. doi:10.1016/j.tiv.2011.05.0
  61. You BR, Moon HJ, Han YH, Park WH. Gallic acid inhibits the growth of HeLa cervical cancer cells via apoptosis and/or necrosis. Food Chem Toxicol. 2010;48(5):1334-1340. doi:10.1016/J.FCT.2010.02.0
  62. Zhou Y, Xu M, Liu Y, et al. Green synthesis of Se/Ru alloy nanoparticles using gallic acid and evaluation of theiranti-invasive effects in HeLa cells. Colloids Surfaces B Biointerfaces. 2016;144:118-124. doi:10.1016/j.colsurfb.2016.04.0
  63. Anjaly K, Tiku AB. Caffeic acid phenethyl ester induces radiosensitization via inhibition of DNA damage repair in androgen‐independent prostate cancer cells. Environ Toxicol. 2022;37(5):995-1006. doi:10.1002/tox.234
  64. Manjinder Kaur, Rajesh Agarwal CA. Gallic acid, a major active constituent of grape seed extract, induces apoptotic death via the activation of p38 MAPK pathway in human prostate carcinoma DU145 cells. Cancer Res. 2007;67(9):496
  65. Chen HM, Wu YC, Chia YC, et al. Gallic acid, a major component of Toona sinensis leaf extracts, contains a ROS-mediated anti-cancer activity in human prostate cancer cells. Cancer Lett. 2009;286(2):161-171. doi:10.1016/j.canlet.2009.05.0
  66. Poudel A, Vadhanam M V, Burlison J. Abstract 4108: Efficacy of ellagic acid and its major urolithin metabolites in inhibiting growth of prostate cancer cells. Cancer Res. 2014;74(19_Supplement):4108-4108. doi:10.1158/1538-7445.AM2014-41
  67. Heidarian E, Keloushadi M, Ghatreh-Samani K, Valipour P. The reduction of IL-6 gene expression, pAKT, pERK1/2, pSTAT3 signaling pathways and invasion activity by gallic acid in prostate cancer PC3 cells. Biomed Pharmacother. 2016;84:264-269. doi:10.1016/j.biopha.2016.09.0
  68. Fahmy UA. Augmentation of fluvastatin cytotoxicity against prostate carcinoma PC3 cell line utilizing alpha lipoic–ellagic acid nanostructured lipid carrier formula. AAPS PharmSciTech. 2018;19(8):3454-3461. doi:10.1208/s12249-018-1199
  69. Malik A, Afaq S, Shahid M, Akhtar K, Assiri A. Influence of ellagic acid on prostate cancer cell proliferation: A caspase–dependent pathway. Asian Pac J Trop Med. 2011;4(7):550-555. doi:10.1016/S1995-7645(11)60144
  70. Riahi-Chebbi I, Souid S, Othman H, et al. The phenolic compound kaempferol overcomes 5-fluorouracil resistance in human resistant LS174 colon cancer cells. Sci Rep. 2019;9(1):195. doi:10.1038/s41598-018-36808-z