SavedAdd your journal

Journals / Sağlık Bilimleri Dergisi / 2026 / Cilt: 33 Sayı: 1

ANTIPROLIFERATIVE AND ANTIOXIDANT EFFECTS OF CARNOSIC ACID ON HUMAN LIVER CANCER CELLS

Uğur Nuri Akın(ERCIYES UNIVERSITY)0009-0009-0495-7663
Elçin Bakır(ERCIYES UNIVERSITY)0000-0001-5333-8273
Aysun Ökçesiz Hacıseyitoğlu(ERCIYES UNIVERSITY)0000-0001-9130-2853
Ayşe Eken(Erciyes Üniversitsi)0000-0003-4830-5770
Pages
60–66
Publication Date
2024-04-01
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

The results suggested that carnosic acid alone or in combination with cisplatin might be a promising agent in the treatment of liver cancer.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:The purpose of the study was to investigate the cytotoxic effects of carnosic acid alone and in combination with cisplatin on human liver cancer cells and their capacity to scavenge reactive oxygen species induced in the presence or absence of hydrogen peroxide.Cytotoxic effects of agents on human liver cancer cells for 24 and 48 hours were evaluated by methyl-thiazol tetrazolium-bromide assay.
📊
Key Findings & Data:Mitochondrial membrane potential were detected JC-1 kit.
💡
Conclusion & Impact:The results suggested that carnosic acid alone or in combination with cisplatin might be a promising agent in the treatment of liver cancer.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:Antioksidanlar · karnosik asit · sisplatin

Abstract

The purpose of the study was to investigate the cytotoxic effects of carnosic acid alone and in combination with cisplatin on human liver cancer cells and their capacity to scavenge reactive oxygen species induced in the presence or absence of hydrogen peroxide.Cytotoxic effects of agents on human liver cancer cells for 24 and 48 hours were evaluated by methyl-thiazol tetrazolium-bromide assay. Mitochondrial membrane potential were detected JC-1 kit. The intracellular reactive oxygen species levels were determined using 2’-7’dichlorofluorescin diacetateassay. According to our findings, both carnosic acid alone and in combination with cisplatin showed cytotoxic effects in human liver cancer cells at 24 and 48 hours of exposure. In particular, it was seen that the cell viability significantly decreased in a dose-dependent manner at 48 hours of exposure, and the combined treatment was found to have a more pronounced cytotoxic effect. In addition, all carnosic acid concentrations alone and in combination with cisplatin were identified to significantly reduce mitochondrial membrane potential. We observed that both carnosic acid alone and in combination with cisplatin lowered intracellular reactive oxygen species levels in the presence or absence of hydrogen peroxide. The results suggested that carnosic acid alone or in combination with cisplatin might be a promising agent in the treatment of liver cancer.

Özet

Bu çalışmanın amacı, karnosikasitin tek başına ve sisplatin ile kombinasyonu insan karaciğer kanseri hücreleri üzerinde sitotoksik etkilerini ve bunların hidrojen peroksit varlığında veya yokluğunda indüklenen reaktif oksijen türlerini temizleme kapasitelerini araştırmaktır. Maddelerin insan karaciğer kanser hücreleri üzerindeki 24 ve 48 saatlik sitotoksik etkileri metil-tiyazol tetrazolyum-bromür testi ile değerlendirildi. Mitokondriyal membran potansiyeli JC-1 kiti ile tespit edildi. Hücre içi reaktif oksijen türlerinin düzeyleri 2’-7'diklorofloresin diasetat yöntemi kullanılarak belirlendi. Bulgularımıza göre, 24 ve 48 saatlik maruziyette karnosikasitin hem tek başına hem de sisplatin ile kombinasyonu insan karaciğer kanser hücrelerinde sitotoksik etkiler gösterdi. Özellikle, 48 saatlik maruziyette doza bağlı bir şekilde hücre canlılığını önemli ölçüde azalttığı görüldü ve kombine tedavinin daha belirgin bir sitotoksik etkiye sahip olduğu bulundu. Ayrıca, tüm karnosik asit konsantrasyonlarının tek başına ve sisplatin ile kombinasyonlarının mitokondriyal membran potansiyelini önemli ölçüde azalttığı belirlendi. Hem karnosikasitin tek başına hem de sisplatin ile kombinasyonu hidrojen peroksit varlığında veya yokluğunda hücre içi reaktif oksijen türlerinin düzeylerini düşürdüğünü gözlemledik. Sonuçlar, karnosikasitin tek başına veya sisplatin ile kombinasyon şeklinde karaciğer kanserinin tedavisinde umut verici bir ajan olabileceğini düşündürdü.

🔖

Cite This Article

Akın, U. N., Bakır, E., Hacıseyitoğlu, A. Ö., Eken, A. (2024). ANTIPROLIFERATIVE AND ANTIOXIDANT EFFECTS OF CARNOSIC ACID ON HUMAN LIVER CANCER CELLS. Sağlık Bilimleri Dergisi, Cilt: 33 Sayı: 1, 60–66. https://doi.org/10.34108/eujhs.1313433

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (35)

  1. Ottoni FM, Gomes ER, Padua RM, Oliveira MC, Silva IT, Alves RJ. Synthesis and cytotoxicity evaluation of glycosidic derivatives of lawsone against breast cancer cell lines. Bioorg Med Chem Lett. 2020; 30(2):126817. doi:10.1016/j.bmcl.2019.126817.
  2. Xiang Q, Ma Y, Dong J, Shen R. Carnosic acid induces apoptosis associated with mitochondrial dysfunction and Akt inactivation in HepG2 cells. Int J Food Sci Nutr. 2015; 66(1):76-84. doi:10.3109/09 637486.2014.953452.
  3. Geng N, Zheng X, Wu M, Yang L, Li X, Chen J. Tannic acid synergistically enhances the anticancer efficacy of cisplatin on liver cancer cells through mitochondria‑mediated apoptosis. Oncol Rep. 2019; 42(5):2108-2116. doi:10.3892/or.2019.728 1.
  4. Zhang X, Li W, Dou X, Nan D, He G. Astaxanthin encapsulated in biodegradable calcium alginate microspheres for the treatment of hepatocellular carcinoma in vitro. Appl Biochem Biotechnol. 2020; 191(2):511-527. doi:10.1007/s12010-019-03174-z.
  5. Liu Y, Whelan RJ, Pattnaik BR, Ludwig K, Subudhi E, Rowland H, et al. Terpenoids from Zingiber officinale (Ginger) induce apoptosis in endometrial cancer cells through the activation of p53. PLoS ONE. 2012;7(12):e53178. doi:10.1371/journal.pone.00 53178.
  6. Lin CY, Chen WJ, Fu RH, Tsai CW. Upregulation of OPA1 by carnosic acid is mediated through induction of IKKγ ubiquitination by parkin and protects against neurotoxicity. Food Chem Toxicol. 2020; 136:110942. doi:10.1016/j.fct.2019.110942.
  7. Liu Y, Zhang Y, Hu M, Li YH, Cao XH. Carnosic acid alleviates brain injury through NF‑κB‑regulated inflammation and caspase‑3‑associated apoptosis in high fat‑induced mouse models. Mol Med Rep. 2019; 20(1):495-504. doi:10.3892/mmr.2019. 10299.
  8. Erkan N, Ayranci G, Ayranci E. Antioxidant activities of rosemary (Rosmarinus officinalis L.) extract, blackseed (Nigella sativa L.) essential oil, carnosic acid, rosmarinic acid and sesamol. Food Chem. 2008; 110(1):76-82. doi:10.1016/j.foodchem. 2008.01.058.
  9. Tsai CW, Lin CY, Lin HH, Chen JH. Carnosic acid, a rosemary phenolic compound, induces apoptosis through reactive oxygen species-mediated p38 activation in human neuroblastoma IMR-32 cells. Neurochem Res. 2011;36(12):2442-2451. doi:10.10 07/s11064-011-0573-4.
  10. Ribeiro-Santos R, Carvalho-Costa D, Cavaleiro C, Costa HS, Albuquerque TG, Castilho MC, et al. A novel insight on an ancient aromatic plant: The rosemary (Rosmarinus officinalis L.). Trends Food Sci Technol. 2015;45(2):355-368. doi:10.1016/j.ti fs.2015.07.015.
  11. Bahri S, Jameleddine S, Shlyonsky V. Relevance of carnosic acid to the treatment of several health disorders: Molecular targets and mechanisms. Biomed Pharmacother. 2016; 84:569-582. doi:10.10 16/j.biopha.2016.09.067.
  12. Zhang X, Chen Y, Cai G, Li X, Wang D. Carnosic acid induces apoptosis of hepatocellular carcinoma cells via ROS-mediated mitochondrial pathway. Chem Biol Interac. 2017; 277:91-100. doi:10.1016/j. cbi.2017.09.005.
  13. de Oliveira MR, da Costa Ferreira G, Peres A, Bosco SMD. Carnosic acid suppresses the H2O2-induced mitochondria-related bioenergetics disturbances and redox impairment in SH-SY5Y cells: Role for Nrf2. Mol Neurobiol. 2018; 55(2):968-979. doi:10.1007/s12035-016-0372-7.
  14. Corveloni AC, Semprebon SC, Baranoski A, Biazi BI, Zanetti TA, Mantovani MS. Carnosic acid exhibits antiproliferative and proapoptotic effects in tumoral NCI-H460 and nontumoral IMR-90 lung cells. J Toxicol Environ Health A. 2020; 83(10):412-421. doi:10.1080/15287394.2020.1767741.
  15. Einbond LS, Wu HA, Kashiwazaki R, He K, Roller M, Su T, et al. Carnosic acid inhibits the growth of ER-negative human breast cancer cells and synergizes with curcumin. Fitoterapia. 2012; 83(7):1160-1168. doi:10.1016/j.fitote.2012.07.006.
  16. Johnson JJ, Syed DN, Heren CR, Suh Y, Adhami VM, Mukhtar H. Carnosol, a dietary diterpene, displays growth inhibitory effects in human prostate cancer PC3 cells leading to G2-phase cell cycle arrest and targets the 5'-AMP-activated protein kinase (AMPK) pathway. Pharm Res. 2008; 25(9):2125-2134. doi:10.1007/s11095-008-9552-0.
  17. El-Huneidi W, Bajbouj K, Muhammad JS, Vinod A, Shafarin J, Khoder G, et al.Carnosic acid induces apoptosis and inhibits Akt/mTOR signaling in human gastric cancer cell lines. Pharmaceuticals. 2021; 14(3):230. doi:10.3390/ph14030230.
  18. Dasari S,Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol. 2014; 740:364-378. doi:10.1016/j.ejphar. 2014.07.025.
  19. Liu W, Wu TC, Hong DM, Hu Y, Fan T, Guo WJ, et al. Carnosic acid enhances the anti-lung cancer effect of cisplatin by inhibiting myeloid-derived suppressor cells. Chin J Nat Med. 2018; 16(12):907-915. doi:10.1016/S1875-5364(18)30132-8.
  20. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1-2):55-63. doi:10.1016/0022-1759(83)90303-4.
  21. Wang H, Joseph JA. Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Rad Biol Med. 1999; 27(5-6):612-616. doi:10.1016/s0891-5849(99)00107-0.
  22. Petiwala SM, Johnson JJ. Diterpenes from rosemary (Rosmarinus officinalis): Defining their potential for anti-cancer activity. Cancer Lett. 2015; 367(2):93-102. doi:10.1016/j.canlet.2015.07.005.
  23. Yesil-Celiktas O, Sevimli C, Bedir E, Vardar-Sukan F. Inhibitory effects of rosemary extracts, carnosic acid and rosmarinic acid on the growth of various human cancer cell lines. Plant Foods Hum Nutr. 2010; 65(2):158-163. doi:10.1007/s11130-010-01 66-4.
  24. Awad MG, Ali RA, Abd El-Monem DD, El-Magd MA. Graviola leaves extract enhances the anticancer effect of cisplatin on various cancer cell lines. Mol Cell Toxicol. 2020; 16:385-399. doi:10.1007/s132 73-020-00092-8.
  25. Kaplan AK, Maras H, Kolsan M, Sitar M, Aktaş RG. Morphological and biochemical effects of carnosic acid on human hepatocellular carcinoma HepG2 cells. Int J Med Surg Sci. 2021; 8(2):1355. doi:10.32 457/ijmss.v8i2.1355.
  26. Su K, Wang CF, Zhang Y, Cai YJ, Zhang YY, Zhao Q. The inhibitory effects of carnosic acid on cervical cancer cells growth by promoting apoptosis via ROS-regulated signaling pathway. Biomed Pharmacother. 2016; 82:180-91. doi:10.1016/j.biopha. 2016.04.056.
  27. Bai N, He K, Roller M, Lai CS, Shao X, Pan MH, et al. Flavonoids and phenolic compounds from Rosmarinus officinalis. J Agric Food Chem. 2010; 58(9):5363-5367. doi:10.1021/jf100332w.
  28. Ossikbayeva S, Khanin M, Sharoni Y, Trachtenberg A, Tuleukhanov S, Sensenig R, et al. Curcumin and carnosic acid cooperate to inhibit proliferation and alter mitochondrial function of metastatic prostate cancer cells. Antioxidants (Basel). 2021; 10(10):1591. doi:10.3390/antiox10101591.
  29. Zhang BB, Wang DG, Guo FF, Xuan C. Mitochondrial membrane potential and reactive oxygen species in cancer stem cells. Fam Cancer. 2015; 14(1):19-23. doi:10.1007/s10689-014-9757-9.
  30. Yang Y, Karakhanova S, Hartwig W, D'Haese JG, Philippov PP, Werner J, et al. Mitochondria and mitochondrial ROS in cancer: Novel targets for anticancer therapy. J Cell Physiol. 2016; 231(12):2570-2581. doi:10.1002/jcp.25349.
  31. Karaca B, Bakır E, Yerer MB, Cumaoglu A, Hamurcu Z, Eken A. Doxazosin and erlotinib have anticancer effects in the endometrial cancer cell and important roles in ERα and Wnt/β-catenin signaling pathways. J Biochem Mol Toxicol. 2021; 35(11):e22905. doi:10.1002/jbt.22905.
  32. Abbasi A, Pakravan N, Hassan ZM. Hyaluronic acid optimises therapeutic effects of hydrogen peroxide-induced oxidative stress on breast cancer. J Cell Physiol. 2021; 236(2):1494-1514. doi:10.1002/jcp. 29957.
  33. Kim S, Kim M, Kang MC, Lee HHL, Cho CH, Choi I, et al. Antioxidant effects of turmeric leaf extract against hydrogen peroxide-induced oxidative stress in vitro in Vero Cells and in vivo in Zebrafish. Antioxidants (Basel). 2021; 10(1):112. doi:10.33 90/antiox10010112.
  34. Wang J,Yi J. Cancer cell killing via ROS: to increase or decrease that is the question. Cancer Biol Ther. 2008; 7(12):1875-1884. doi:10.4161/cbt.7.12.70 67.
  35. Hu Y, Zhang N, Fan Q, Lin M, Zhang C, Fan G, et al. Protective efficacy of carnosic acid against hydrogen peroxide induced oxidative injury in HepG2 cells through the SIRT1 pathway. Can J Physiol Pharmacol. 2015; 93(8):625-631. doi:10.1139/cjpp-2014-0513.