Investigation of the effects of Protocatechuic acid on apoptosis, oxidant and antioxidant status in Caco-2 colorectal cancer cells

Year 2024, Volume: 8 Issue: 2, 136 - 141, 30.08.2024

Fatma Yıldız

https://doi.org/10.30565/medalanya.1503397

Abstract

Aim: Protocatechuic acid (PCA) is one of the common phenolic acids found in many foods and plants and it has multiple biological activities. Although PCA has been investigated for its antioxidant, anti-inflammatory, and anticancer effects in various cell lines, its effects on molecules involved in the apoptotic pathway, especially in human colon cancer (Caco-2) cells, have not been fully elucidated. This study aimed to investigate the effects of PCA on possible oxidant, antioxidant, and apoptosis mechanisms in Caco-2 cells, depending on dose and time.

Methods: In the experimental study, 4 groups were created: control (K), PCA (250-500-1000 µM). Total oxidant capacity (TOC), total antioxidant capacity (TAC), Oxidative stress index (OSI), Bax, Bad, Bcl-2, Bcl-xl, and Caspase 9 protein levels were determined by the ELISA method in the cell lysates obtained from the groups.

Results: The results showed that PCA treatment had apoptotic effects on Caco-2 cells at 24 and 48 h. PCA also decreased OSI levels by increasing TAC levels and decreasing TOC levels in a dose-dependent manner.

Conclusion: As a result, it was determined that PCA has an apoptotic effect on the Caco-2 cell line and can be useful in the prevention and/or treatment of colon cancer.

Keywords

Colon cancer, Caco-2, Protocatechuic acid, Apoptosis, Oxidative stress

Protokatekuik asidin Caco-2 kolorektal kanser hücrelerinde apoptoz, oksidan ve antioksidan durum üzerine etkilerinin araştırılması

Abstract

Amaç: Protokatekuik asit (PCA), birçok biyolojik aktiviteye sahip birçok gıda ve bitkide bulunan yaygın fenolik asitlerden biridir. PCA'nın çeşitli hücre hatlarında antiinflamatuvar, antioksidan, antikanser etkileri araştırılmasına rağmen insan kolon kanseri (Caco-2) hücrelerinde özellikle de apoptotik yolaklakta yer alan moleküller üzerindeki etkileri tam olarak aydınlatılamamıştır. Bu çalışmanın amacı PCA'nın Caco-2 hücrelerinde doza ve zamana bağlı olarak olası oksidan, antioksidan ve apoptoz mekanizmaları üzerindeki etkilerini araştırmaktır.

Yöntem: Deneysel çalışmada kontrol (K), PCA (250-500-1000 µM) olmak üzere 4 grup oluşturulmuştur. Gruplardan elde edilen hücre lizatlarında toplam oksidan kapasite (TOC), toplam antioksidan kapasite (TAC), Oksidatif stres indeksi (OSI), Bax, Bad, Bcl-2, Bcl-xl, Kaspaz 9 protein seviyeleri ELISA yöntemiyle belirlenmiştir.

Bulgular: Sonuçlar PCA tedavisinin Caco-2 hücrelerinde 24 ve 48 saatte apoptotik etkilere sahip olduğunu göstermiştir. Ayrıca PCA doza bağlı bir şekilde TAC seviyelerini artırırken TOC seviyelerini azaltarak OSI seviyelerini de azaltmıştır.

Sonuç: Sonuç olarak PCA'nın Caco-2 hücre hattında apoptotik etkiye sahip olduğu ve kolon kanserinin önlenmesinde ve/veya tedavisinde yararlı olabileceği belirlenmiştir.

Keywords

Kolon kanseri, Caco-2, Protokatekuik asit, Apoptoz, Oksidatif stres

References

• 1. Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019;16(12):713-32. doi:10.1038/s41575-019-0189-8.
• 2. Esmeeta A, Adhikary S, Dharshnaa V, Swarnamughi P, Maqsummiya ZU, Banerjee A et al. Plant-derived bioactive compounds in colon cancer treatment: An updated review. Biomed Pharmacother. 2022;153,113384. doi: 10.1016/j.biopha.2022.113384.
• 3. Bayram D. Investigation of Appoptotic Effect of Silibinin on CCL-228-SW 480 Column Cancer Cell Line: An In Vitro Study. Süleyman Demirel University Journal of Health Sciences, 2017;8(2):1-7. doi: 10.22312/sdusbed.287465.
• 4. Secme M, Mutlu D, Elmas L, Arslan S. Assessing effects of caffeic acid on cytotoxicity, apoptosis, invasion, GST enzyme activity, oxidant, antioxidant status and micro-RNA expressions in HCT116 colorectal cancer cells. S Afr J Bot. 2023;157:19-26. doi: 10.1016/j.sajb.2023.03.046.
• 5. Kasprzak-Drozd K, Oniszczuk T, Stasiak M, Oniszczuk A. Beneficial effects of phenolic compounds on gut microbiota and metabolic syndrome. Int J Mol Sci. 2021;22(7):3715. doi: 10.3390/ijms22073715.
• 6. Li F, Qasim S, Li D, Dou QP. Updated review on green tea polyphenol epigallocatechin-3-gallate as a cancer epigenetic regulator. Semin Cancer Biol. 2022;83;335-52. doi: 10.1016/j.semcancer.2020.11.018.
• 7. Gupta, J, Ahuja A, Gupta R. Green approaches for cancers management: An effective tool for health care. AntiCancer Agents Med Chem. 2022;22(1):101-14. doi: 10.2174/1871520621666210119091826.
• 8. Kakkar S, Bais SA. Review on Protocatechuic Acid and Its Pharmacological Potential. ISRN Pharmacol. 2014;2014:952943. doi: 10.1155/2014/952943
• 9. Cadena-Iñiguez J, Santiago-Osorio E, Sánchez-Flores N, Salazar-Aguilar S, Soto-Hernández RM, Riviello-Flores MDLL et al. The Cancer-Protective Potential of Protocatechuic Acid: A Narrative Review. Molecules. 2024;29(7):1439. doi: 10.3390/molecules29071439.
• 10. Yang X, Sun X, Zhou F, Xiao S, Zhong L, Hu S et al. Protocatechuic acid alleviates dextran-sulfate-sodium-induced ulcerative colitis in mice via the regulation of intestinal flora and ferroptosis. Molecules 2023;28(9):3775. doi: 10.3390/molecules28093775.
• 11. Ya F, Li K, Chen H, Tian Z, Fan D, Shi Y et al. Protocatechuic Acid Protects Platelets from Apoptosis via Inhibiting Oxidative Stress-Mediated PI3K/Akt/GSK3β Signaling. Thromb Haemost. 2021; 121: 931–43. doi: 10.1055/s-0040-1722621.
• 12. AbouAitah K, Piotrowska U, Wojnarowicz J, Swiderska-Sroda A, El-Desoky AHH, Lojkowski W. Enhanced Activity and Sustained Release of Protocatechuic Acid, a Natural Antibacterial Agent, from Hybrid Nanoformulations with Zinc Oxide Nanoparticles. Int J Mol Sci. 2021;22(10):5287. doi: 10.3390/ijms22105287.
• 13. Okuyan D. Apoptosis. Selçuk University Faculty of Science Journal of Science, 2023;49(1):1-10. doi: 10.35238/sufefd.1210651.
• 14. Samsunlu ET, Lenger ÖF. Apoptotic Effects of Phytochemicals on Cancer Cells. Osmaniye Korkut Ata University Journal of The Institute of Science and Technology. 2023;6(2):1662-74.
• 15. Navazani P, Vaseghi S, Hashemi M, Shafaati MR, Nasehi M. Effects of Treadmill Exercise on the Expression Level of BAX, BAD, BCL-2, BCL-XL, TFAM, and PGC-1α in the Hippocampus of Thimerosal-Treated Rats. Neurotox Res. 2021;39(4):1274-84. doi: 10.1007/s12640-021-00370-w.
• 16. Yıldız F, Eciroglu H, Övey İS, Avnioğlu S. Effect of combination treatment of protocatechuic acid with 5-fluorouracil and oxaliplatin on colon cancer Caco-2 cell line. IJEB. 2023;61 (3):151-8. doi: 10.56042/ijeb.v61i03.65610.
• 17. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38(12):1103-11. doi: 10.1016/j.clinbiochem.2005.08.008.
• 18. Deska M, Romuk E, Segiet OA, Bula G, Truchanowski W, Stolecka D et al. Oxidative stress and angiogenesis in primary hyperparathyroidism. Eur Surg. 2017;49(3):118-26. doi: 10.1007/s10353-016-0457-6.
• 19. Acquaviva R, Tomasello B, Di Giacomo C, Santangelo R, La Mantia A, Naletova I et al. Protocatechuic Acid, a Simple Plant Secondary Metabolite, Induced Apoptosis by Promoting Oxidative Stress through HO-1 Downregulation and P21 Upregulation in Colon Cancer Cells. Biomolecules. 2021;11(10):1485. doi: 10.3390/biom11101485.
• 20. Xiao K, Zhou M, Lv Q, He P, Qin X, Wang D et al. Protocatechuic Acid and Quercetin Attenuate ETEC-Caused IPEC-1 Cell Inflammation and Injury Associated with Inhibition of Necroptosis and Pyroptosis Signaling Pathways. J Anim Sci Biotechnol. 2023;14(1):5. doi: 10.1186/s40104-022-00816-x.
• 21. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35(4):495-516. doi:10.1080/01926230701320337.
• 22. Huang J, Zhu X, Wang H, Han S, Liu L, Xie Y et al. Role of gambogic acid and NaI (131) in A549/DDP cells. Oncol Lett. 2017;13(1):37–44. doi: 10.3892/ol.2016.5435
• 23. Lee WJ, Lee SH. Protocatechuic Acid Protects Hepatocytes against Hydrogen Peroxide-Induced Oxidative Stress. Curr Res Food Sci. 2022;5:222–27. doi: 10.1016/j.crfs.2022.01.006.
• 24. Jaganathan SK, Mandal M. Honey constituents and its apoptotic effect in colon cancer cells. JAAS. 2009;1(2):29-36. doi: 10.3896/IBRA.4.01.2.02.
• 25. Farombi EO, Adedara IA, Awoyemi OV, Njoku CR, Micah GO, Esogwa CU et al. Dietary Protocatechuic Acid Ameliorates Dextran Sulphate Sodium-Induced Ulcerative Colitis and Hepatotoxicity in Rats. Food Funct. 2016; 7: 913–21. doi: 10.1039/C5FO01228G.