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Evaluation of the Cytotoxic Effect and Possible Mechanisms of Carnosol and Carnosic Acid in Human Endometrioid Ovarian Adenocarcinoma Cell Line MDAH-2774 Cells

Year 2024, Volume: 26 Issue: 3, 322 - 328, 24.12.2024

Abstract

Objective: Ovarian cancer is one of the most lethal forms of gynecological malignancies in women and is often detected at an advanced stage. Cytotoxic treatments have been investigated to sensitize cancer cells. Naturally occurring products are becoming an attractive method for suppressing cancer growth because of their cytotoxic properties. Both carnosol and carnosic acid are diterpenoids with antioxidant, anti- inflammatory, anti-proliferative, and anti-cancer activities. The present study aims to investigate the effects of both carnosol and carnosic acid on the MDAH-2774 cell line.
Material and Methods: Different concentrations and time intervals were used in the present study. We employed MTT to show cell survival in the presence and absence of carnosol and/or carnosic acid. To understand the mechanisms behind the effects of the agents on cell survival, total antioxidant capacity was evaluated.
Results: Our results showed that the agents, alone and more so in combination, successfully reduced the viability of MDAH- 2774 cells. Total antioxidant capacity analysis revealed that the compounds had high antioxidant capacities both when used alone and when combined.
Conclusion: Our study determined the cytotoxic effects of carnosol and carnosic acid, both when used alone and in combination. These effects may be attributed to their antioxidant properties, with the combined form exhibiting a more pronounced impact.

References

  • Ayla Ş, Bilir A, Ertürkoğlu Ş et al. Effects of different drug treatments on the proliferation of human ovarian carcinoma cell line MDAH-2774. Turkish J Med Sci. 2018;48(2):441–448.
  • Smolle E, Taucher V, Pichler M et al. Targeting signaling pathways in epithelial ovarian cancer. Int J Mol Sci. 2013;14(5):9536–9555.
  • Zalewski M, Kulbacka J, Saczko J et al. Valspodar-modulated chemotherapy in human ovarian cancer cells SK-OV-3 and MDAH-2774. Bosn J Basic Med Sci. 2019;19(3):234–241.
  • Gilloteaux J, Lau HL, Gourari I et al. Apatone® induces endometrioid ovarian carcinoma (MDAH 2774) cells to undergo karyolysis and cell death by autoschizis: A potent and safe anticancer treatment. Transl Res Anat. 2015;1(2015):25–39.
  • Choi SM, Kim DH, Chun KS, Choi JS. Carnosol induces apoptotic cell death through ROS-dependent inactivation of STAT3 in human melanoma G361 cells. Appl Biol Chem. 2019;62:1-11.
  • Dai L, Li C, Shedden KA et al. Comparative Proteomic Study of Two Closely Related Ovarian Endometrioid Adenocarcinoma Cell Lines Using cIEF Fractionation and Pathway Analysis. Electrophoresis. 2009;30(7):1119-1131.
  • Corveloni AC, Semprebon SC, Baranoski A et al. 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.
  • Vergara D, Simeone P, Bettini Set al. Antitumor activity of the dietary diterpene carnosol against a panel of human cancer cell lines. Food Funct. 2014;5(6):1261–1269.
  • Chun K-S, Kundu J, Chae IG et al. Carnosol: A Phenolic Diterpene With Cancer Chemopreventive Potential. J Cancer Prev. 2014;19(2):103–110.
  • Mahdavi R, Faramarzi E, Seyedrezazadeh E et al. Evaluation of oxidative stress, antioxidant status and serum vitamin C levels in cancer patients. Biol Trace Elem Res. 2009;130(1):1–6.
  • Erten Şener D, Gönenç A, Akıncı M et al. Lipid peroxidation and total antioxidant status in patients with breast cancer. Cell Biochem Funct. 2007;25(4):377–382.
  • Kocot J, Kiełczykowska M, Da̧browski W et al. Total antioxidant status value and superoxide dismutase activity in human colorectal cancer tissue depending on the stage of the disease: A pilot study. Adv Clin Exp Med. 2013;22(3):431–437.
  • Abbasalizad Farhangi M, Vajdi M. Dietary Total Antioxidant Capacity (TAC) Significantly Reduces the Risk of Site-Specific Cancers: An Updated Systematic Review and Meta-Analysis. Nutr Cancer. 2021;73(5):721–739.
  • Shao N, Mao J, Xue L et al. Carnosic acid potentiates the anticancer effect of temozolomide by inducing apoptosis and autophagy in glioma. J Neurooncol. 2019;141(2):277–288.
  • Lin KI, Lin CC, Kuo SM et al. Carnosic acid impedes cell growth and enhances anticancer effects of carmustine and lomustine in melanoma. Biosci Rep. 2018;38(4):1–11.
  • Ossikbayeva S, Khanin M, Sharoni Y et al. Curcumin and carnosic acid cooperate to inhibit proliferation and alter mitochondrial function of metastatic prostate cancer cells. Antioxidants. 2021;10(10):1591.
  • O’neill EJ, Den Hartogh DJ, Azizi K et al. Anticancer properties of carnosol: A summary of in vitro and in vivo evidence. Antioxidants. 2020;9(10):1–22.
  • Duran T, Koçak N, Karaselek M. Carnosol and carnosic acid may be a promising anticancer agent in non-small cell lung cancer treatment. Cukurova Med J. 2024;49(1):81–88.
  • Petiwala SM, Johnson JJ. Diterpenes from rosemary (Rosmarinus officinalis): Defining their potential for anti-cancer activity. Cancer Lett. 2015;367(2):93–102.
  • Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem. 2004;37(4):277–285.
  • Zunino SJ, Storms DH. Carnosol delays chemotherapy-induced DNA fragmentation and morphological changes associated with apoptosis in leukemic cells. Nutr Cancer. 2009;61(1):94–102.
  • Johnson JJ. Carnosol: A promising anti-cancer and anti-inflammatory agent. Cancer Lett. 2011;4(164):1–7.
  • Giacomelli C, Daniele S, Natali L et al. Carnosol controls the human glioblastoma stemness features through the epithelial-mesenchymal transition modulation and the induction of cancer stem cell apoptosis. Sci Rep. 2017;7(1):1–17.
  • Li A, Cao W. Downregulation of SODD mediates carnosol-induced reduction in cell proliferation in esophageal adenocarcinoma cells. Sci Rep. 2023;13(1):1–7.
  • Feng JF, Lu L, Zeng P et al. Serum total oxidant/antioxidant status and trace element levels in breast cancer patients. Int J Clin Oncol. 2012;17(6):575–583.
  • Du XF, Zhang LL, Zhang DZ et al. Clinical significance of serum total oxidant/antioxidant status in patients with operable and advanced gastric cancer. Onco Targets Ther. 2018;11:6767–6775.
  • Ching S, Ingram D, Hahnel R et al. Serum levels of micronutrients, antioxidants and total antioxidant status predict risk of breast cancer in a case control study. J Nutr. 2002;132(2):303–306.
  • Zahra KF, Lefter R, Ali A et al. The Involvement of the Oxidative Stress Status in Cancer Pathology: A Double View on the Role of the Antioxidants. Oxid Med Cell Longev. 2021;2021:9965916
  • Pawlowska E, Szczepanska J, Blasiak J. Pro- And antioxidant effects of Vitamin C in cancer in correspondence to its dietary and pharmacological concentrations. Oxid Med Cell Longev. 2019;2019:7286737.
  • Yun J, Mullarky E, Lu C, et al. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science. 2015;350(6266):1391-1396.
  • Kelkel M, Jacob C, Dicato M et al. Potential of the dietary antioxidants resveratrol and curcumin in prevention and treatment of hematologic malignancies. Molecules. 2010;15(10):7035-7074.
  • Kong Y, Ma W, Liu X et al. Cytotoxic activity of curcumin towards CCRF-CEM leukemia cells and its effect on DNA damage. Molecules. 2009;14(12):5328–5338.

İNSAN ENDOMETRİOİD OVER ADENOKARSİNOM HÜCRE HATTI MDAH-2774 HÜCRELERİNDE KARNOSOL VE KARNOSİK ASİTİN SİTOTOKSİK ETKİSİNİN VE OLASI MEKANİZMALARININ DEĞERLENDİRİLMESİ

Year 2024, Volume: 26 Issue: 3, 322 - 328, 24.12.2024

Abstract

Amaç: Over kanseri, kadınlarda en yüksek ölüm oranına sahip olan ve genellikle ileri evrede teşhis edilebilen bir jinekolojik kanser türüdür. Kanser hücrelerini duyarlı hale getirmek için sitotoksik tedaviler araştırılmaktadır. Sitotoksik etkileri olduğu bilinen bitki kaynaklı ürünlerin kullanımı, kanser büyümesini baskılamada ilgi çekici bir yöntem haline gelmiştir. Hem karnosol hem de karnosik asit, antioksidan, anti-inflamatuvar, anti-proliferatif ve antikanser aktivitelere sahip olan bitkisel diterpenoidlerdir. Yaptığımız bu çalışmanın amacı hem karnosol hem de karnosik asidin MDAH-2774 over endometrioid kanseri hücre hattı üzerindeki etkilerini araştırmaktır.
Gereç ve Yöntemler: Çalışmamızda farklı konsantrasyonlar ve zaman aralıkları kullanılmıştır. Karnosol ve/veya karnosik asidin varlığında ve yokluğunda hücre canlılığı üzerine olan etkiler, MTT analizi ile saptanmıştır. Ajanların hücre canlılığı üzerindeki etkilerinin ardındaki mekanizmayı anlamak için hücrelerin toplam antioksidan durumu değerlendirilmiştir.
Bulgular: Sonuçlarımız, ajanların tek başlarına ve daha çok da kombine halde MDAH-2774 hücre canlılığını başarıyla azalttığını göstermiştir. Toplam antioksidan durum analizi bileşiklerin ayrı ayrı ve kombine halde antioksidan kapasitelerinin yüksekliğini göstermiştir.
Sonuç: Çalışmamız, karnosol ve karnosik asidin tek başına ve kombine halde gösterdikleri sitotoksik etkinin onların antioksidan etkileriyle ilişkili olabileceğini ve bu etkinin kombine halde daha güçlü olduğunu saptamıştır.

References

  • Ayla Ş, Bilir A, Ertürkoğlu Ş et al. Effects of different drug treatments on the proliferation of human ovarian carcinoma cell line MDAH-2774. Turkish J Med Sci. 2018;48(2):441–448.
  • Smolle E, Taucher V, Pichler M et al. Targeting signaling pathways in epithelial ovarian cancer. Int J Mol Sci. 2013;14(5):9536–9555.
  • Zalewski M, Kulbacka J, Saczko J et al. Valspodar-modulated chemotherapy in human ovarian cancer cells SK-OV-3 and MDAH-2774. Bosn J Basic Med Sci. 2019;19(3):234–241.
  • Gilloteaux J, Lau HL, Gourari I et al. Apatone® induces endometrioid ovarian carcinoma (MDAH 2774) cells to undergo karyolysis and cell death by autoschizis: A potent and safe anticancer treatment. Transl Res Anat. 2015;1(2015):25–39.
  • Choi SM, Kim DH, Chun KS, Choi JS. Carnosol induces apoptotic cell death through ROS-dependent inactivation of STAT3 in human melanoma G361 cells. Appl Biol Chem. 2019;62:1-11.
  • Dai L, Li C, Shedden KA et al. Comparative Proteomic Study of Two Closely Related Ovarian Endometrioid Adenocarcinoma Cell Lines Using cIEF Fractionation and Pathway Analysis. Electrophoresis. 2009;30(7):1119-1131.
  • Corveloni AC, Semprebon SC, Baranoski A et al. 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.
  • Vergara D, Simeone P, Bettini Set al. Antitumor activity of the dietary diterpene carnosol against a panel of human cancer cell lines. Food Funct. 2014;5(6):1261–1269.
  • Chun K-S, Kundu J, Chae IG et al. Carnosol: A Phenolic Diterpene With Cancer Chemopreventive Potential. J Cancer Prev. 2014;19(2):103–110.
  • Mahdavi R, Faramarzi E, Seyedrezazadeh E et al. Evaluation of oxidative stress, antioxidant status and serum vitamin C levels in cancer patients. Biol Trace Elem Res. 2009;130(1):1–6.
  • Erten Şener D, Gönenç A, Akıncı M et al. Lipid peroxidation and total antioxidant status in patients with breast cancer. Cell Biochem Funct. 2007;25(4):377–382.
  • Kocot J, Kiełczykowska M, Da̧browski W et al. Total antioxidant status value and superoxide dismutase activity in human colorectal cancer tissue depending on the stage of the disease: A pilot study. Adv Clin Exp Med. 2013;22(3):431–437.
  • Abbasalizad Farhangi M, Vajdi M. Dietary Total Antioxidant Capacity (TAC) Significantly Reduces the Risk of Site-Specific Cancers: An Updated Systematic Review and Meta-Analysis. Nutr Cancer. 2021;73(5):721–739.
  • Shao N, Mao J, Xue L et al. Carnosic acid potentiates the anticancer effect of temozolomide by inducing apoptosis and autophagy in glioma. J Neurooncol. 2019;141(2):277–288.
  • Lin KI, Lin CC, Kuo SM et al. Carnosic acid impedes cell growth and enhances anticancer effects of carmustine and lomustine in melanoma. Biosci Rep. 2018;38(4):1–11.
  • Ossikbayeva S, Khanin M, Sharoni Y et al. Curcumin and carnosic acid cooperate to inhibit proliferation and alter mitochondrial function of metastatic prostate cancer cells. Antioxidants. 2021;10(10):1591.
  • O’neill EJ, Den Hartogh DJ, Azizi K et al. Anticancer properties of carnosol: A summary of in vitro and in vivo evidence. Antioxidants. 2020;9(10):1–22.
  • Duran T, Koçak N, Karaselek M. Carnosol and carnosic acid may be a promising anticancer agent in non-small cell lung cancer treatment. Cukurova Med J. 2024;49(1):81–88.
  • Petiwala SM, Johnson JJ. Diterpenes from rosemary (Rosmarinus officinalis): Defining their potential for anti-cancer activity. Cancer Lett. 2015;367(2):93–102.
  • Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem. 2004;37(4):277–285.
  • Zunino SJ, Storms DH. Carnosol delays chemotherapy-induced DNA fragmentation and morphological changes associated with apoptosis in leukemic cells. Nutr Cancer. 2009;61(1):94–102.
  • Johnson JJ. Carnosol: A promising anti-cancer and anti-inflammatory agent. Cancer Lett. 2011;4(164):1–7.
  • Giacomelli C, Daniele S, Natali L et al. Carnosol controls the human glioblastoma stemness features through the epithelial-mesenchymal transition modulation and the induction of cancer stem cell apoptosis. Sci Rep. 2017;7(1):1–17.
  • Li A, Cao W. Downregulation of SODD mediates carnosol-induced reduction in cell proliferation in esophageal adenocarcinoma cells. Sci Rep. 2023;13(1):1–7.
  • Feng JF, Lu L, Zeng P et al. Serum total oxidant/antioxidant status and trace element levels in breast cancer patients. Int J Clin Oncol. 2012;17(6):575–583.
  • Du XF, Zhang LL, Zhang DZ et al. Clinical significance of serum total oxidant/antioxidant status in patients with operable and advanced gastric cancer. Onco Targets Ther. 2018;11:6767–6775.
  • Ching S, Ingram D, Hahnel R et al. Serum levels of micronutrients, antioxidants and total antioxidant status predict risk of breast cancer in a case control study. J Nutr. 2002;132(2):303–306.
  • Zahra KF, Lefter R, Ali A et al. The Involvement of the Oxidative Stress Status in Cancer Pathology: A Double View on the Role of the Antioxidants. Oxid Med Cell Longev. 2021;2021:9965916
  • Pawlowska E, Szczepanska J, Blasiak J. Pro- And antioxidant effects of Vitamin C in cancer in correspondence to its dietary and pharmacological concentrations. Oxid Med Cell Longev. 2019;2019:7286737.
  • Yun J, Mullarky E, Lu C, et al. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science. 2015;350(6266):1391-1396.
  • Kelkel M, Jacob C, Dicato M et al. Potential of the dietary antioxidants resveratrol and curcumin in prevention and treatment of hematologic malignancies. Molecules. 2010;15(10):7035-7074.
  • Kong Y, Ma W, Liu X et al. Cytotoxic activity of curcumin towards CCRF-CEM leukemia cells and its effect on DNA damage. Molecules. 2009;14(12):5328–5338.
There are 32 citations in total.

Details

Primary Language Turkish
Subjects Health Services and Systems (Other)
Journal Section Özgün Araştırma
Authors

Hazal Demir 0000-0002-2278-2651

Hatice Örs 0009-0002-2490-2095

Ebru Alimoğulları 0000-0002-9557-3631

Aslı Ceylan 0000-0001-6681-606X

Publication Date December 24, 2024
Submission Date July 30, 2024
Acceptance Date August 20, 2024
Published in Issue Year 2024 Volume: 26 Issue: 3

Cite

APA Demir, H., Örs, H., Alimoğulları, E., Ceylan, A. (2024). İNSAN ENDOMETRİOİD OVER ADENOKARSİNOM HÜCRE HATTI MDAH-2774 HÜCRELERİNDE KARNOSOL VE KARNOSİK ASİTİN SİTOTOKSİK ETKİSİNİN VE OLASI MEKANİZMALARININ DEĞERLENDİRİLMESİ. The Journal of Kırıkkale University Faculty of Medicine, 26(3), 322-328.
AMA Demir H, Örs H, Alimoğulları E, Ceylan A. İNSAN ENDOMETRİOİD OVER ADENOKARSİNOM HÜCRE HATTI MDAH-2774 HÜCRELERİNDE KARNOSOL VE KARNOSİK ASİTİN SİTOTOKSİK ETKİSİNİN VE OLASI MEKANİZMALARININ DEĞERLENDİRİLMESİ. Kırıkkale Uni Med J. December 2024;26(3):322-328.
Chicago Demir, Hazal, Hatice Örs, Ebru Alimoğulları, and Aslı Ceylan. “İNSAN ENDOMETRİOİD OVER ADENOKARSİNOM HÜCRE HATTI MDAH-2774 HÜCRELERİNDE KARNOSOL VE KARNOSİK ASİTİN SİTOTOKSİK ETKİSİNİN VE OLASI MEKANİZMALARININ DEĞERLENDİRİLMESİ”. The Journal of Kırıkkale University Faculty of Medicine 26, no. 3 (December 2024): 322-28.
EndNote Demir H, Örs H, Alimoğulları E, Ceylan A (December 1, 2024) İNSAN ENDOMETRİOİD OVER ADENOKARSİNOM HÜCRE HATTI MDAH-2774 HÜCRELERİNDE KARNOSOL VE KARNOSİK ASİTİN SİTOTOKSİK ETKİSİNİN VE OLASI MEKANİZMALARININ DEĞERLENDİRİLMESİ. The Journal of Kırıkkale University Faculty of Medicine 26 3 322–328.
IEEE H. Demir, H. Örs, E. Alimoğulları, and A. Ceylan, “İNSAN ENDOMETRİOİD OVER ADENOKARSİNOM HÜCRE HATTI MDAH-2774 HÜCRELERİNDE KARNOSOL VE KARNOSİK ASİTİN SİTOTOKSİK ETKİSİNİN VE OLASI MEKANİZMALARININ DEĞERLENDİRİLMESİ”, Kırıkkale Uni Med J, vol. 26, no. 3, pp. 322–328, 2024.
ISNAD Demir, Hazal et al. “İNSAN ENDOMETRİOİD OVER ADENOKARSİNOM HÜCRE HATTI MDAH-2774 HÜCRELERİNDE KARNOSOL VE KARNOSİK ASİTİN SİTOTOKSİK ETKİSİNİN VE OLASI MEKANİZMALARININ DEĞERLENDİRİLMESİ”. The Journal of Kırıkkale University Faculty of Medicine 26/3 (December 2024), 322-328.
JAMA Demir H, Örs H, Alimoğulları E, Ceylan A. İNSAN ENDOMETRİOİD OVER ADENOKARSİNOM HÜCRE HATTI MDAH-2774 HÜCRELERİNDE KARNOSOL VE KARNOSİK ASİTİN SİTOTOKSİK ETKİSİNİN VE OLASI MEKANİZMALARININ DEĞERLENDİRİLMESİ. Kırıkkale Uni Med J. 2024;26:322–328.
MLA Demir, Hazal et al. “İNSAN ENDOMETRİOİD OVER ADENOKARSİNOM HÜCRE HATTI MDAH-2774 HÜCRELERİNDE KARNOSOL VE KARNOSİK ASİTİN SİTOTOKSİK ETKİSİNİN VE OLASI MEKANİZMALARININ DEĞERLENDİRİLMESİ”. The Journal of Kırıkkale University Faculty of Medicine, vol. 26, no. 3, 2024, pp. 322-8.
Vancouver Demir H, Örs H, Alimoğulları E, Ceylan A. İNSAN ENDOMETRİOİD OVER ADENOKARSİNOM HÜCRE HATTI MDAH-2774 HÜCRELERİNDE KARNOSOL VE KARNOSİK ASİTİN SİTOTOKSİK ETKİSİNİN VE OLASI MEKANİZMALARININ DEĞERLENDİRİLMESİ. Kırıkkale Uni Med J. 2024;26(3):322-8.

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