Research Article
Karnosol ve karnosik asit küçük hücreli dışı akciğer kanseri tedavisinde umut verici bir antikanser ajanı olabilir
Abstract
Amaç: Bu çalışma, karnosol ve karnosik asidin küçük hücreli dışı akciğer kanseri (KHDAK) hücre dizileri üzerindeki olası antikanser ve apoptotik etkisini in vitro olarak değerlendirmeyi amaçladı.
Gereç ve Yöntem: Çalışmada üç farklı KHDAK hücre hattı (H441, H520 ve H661) kullanılmış olup, tüm hücre hatlarında uygulama (karnosol ve karnosik asit uygulanmış) ve kontrol (uygulama yapılmayan) grupları oluşturulmuştur. IC50 dozları KHDAK hücre hatlarında MTT yöntemiyle belirlendi ve apoptozla ilişkili genlerin (Bax, Bak, kaspaz-3, p53, c-Myc, Bcl-2 ve Bcl-XL) ekspresyon seviyelerindeki değişiklikler gerçek zamanlı polimeraz zincir reaksiyonu (qPCR) ile gösterildi ve apoptoz akış sitometrisi ile doğrulandı. Tedavi grubu ve kontrol grubu sonuçları karşılaştırıldı.
Bulgular: Karnosol ve karnosik asidin IC50 dozları sırasıyla belirlendi; H441 için 60 µM, H661 için 20 µM, H520 için 40 µM, H441 için 20 µM, H661 için 40 µM, H520 için 40 µM. Karnosol uygulaması, çalışılan akciğer kanseri hücre hatlarında Bax, Bak, kaspaz-3 ve p53 ekspresyonunu arttırdı ancak Bcl-XL ekspresyonunu azalttı. Karnosik asit tedavisi apoptotik Bax, Bak, kaspaz-3 ve p53 ekspresyonunu arttırdı ancak antiapoptotik Bcl-2 ve Bcl-XL ekspresyonunu azalttı (p<0.05).
Sonuç: Bu çalışmada karnosol ve karnosik asidin KHDAK hücreleri üzerinde apoptotik etkileri olduğu gösterilmiştir. Bu ajanlar haklarında daha detaylı çalışmalar yapılmasıyla gelecekte KHDAK tedavisinde kullanılabilecek umut verici bir ajanlar olabilecektir.
References
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7-30.
- Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424.
- Ngo SN, Williams DB, Head RJ. Rosemary and cancer prevention: preclinical perspectives. Crit Rev Food Sci Nutr. 2011;51:946-54.
- Moore J, Yousef M, Tsiani E. Anticancer effects of rosemary (Rosmarinus officinalis L.) extract and rosemary extract polyphenols. Nutrients. 2016;8:731.
- 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;65:158-63.
- Johnson JJ. Carnosol: a promising anti-cancer and anti-inflammatory agent. Cancer Lett. 2011;305:1-7.
- Kalantar H, Sadeghi E, Abolnezhadian F, Goudarzi M, Hemmati AA, Basir Z, et al. Carnosol attenuates bleomycin-induced lung damage via suppressing fibrosis, oxidative stress and inflammation in rats. Life Sci. 2021;287:120059.
- Farhadi F, Baradaran Rahimi V, Mohamadi N, Askari VR. Effects of rosmarinic acid, carnosic acid, rosmanol, carnosol, and ursolic acid on the pathogenesis of respiratory diseases. Biofactors. 2023;49:478-501.
- Cattaneo L, Cicconi R, Mignogna G, Giorgi A, Mattei M, Graziani G, et al. Anti-proliferative effect of Rosmarinus officinalis L. extract on human melanoma A375 cells. PLoS One. 2015;10:e0132439.
- Kontogianni VG, Tomic G, Nikolic I, Nerantzaki AA, Sayyad N, Stosic-Grujicic S et al. Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity. Food Chem. 2013;136:120-9.
- Cheung S, Tai J. Anti-proliferative and antioxidant properties of rosemary Rosmarinus officinalis. Oncol Rep. 2007;17:1525-31.
- Xavier CP, Lima CF, Fernandes-Ferreira M, Pereira-Wilson C. Salvia fruticosa, Salvia officinalis, and rosmarinic acid induce apoptosis and inhibit proliferation of human colorectal cell lines: the role in MAPK/ERK pathway. Nutr Cancer. 2009;61:564-71.
- Wei FX, Liu JX, Wang L, Li HZ, Luo JB. Expression of bcl-2 and bax genes in the liver cancer cell line HepG2 after apoptosis induced by essential oils from Rosmarinus officinalis. Zhong Yao Cai. 2008;31:877-9.
- Steiner M, Priel I, Giat J, Levy J, Sharoni Y, Danilenko M. Carnosic acid inhibits proliferation and augments differentiation of human leukemic cells induced by 1,25-dihydroxyvitamin D3 and retinoic acid. Nutr Cancer. 2001;41:135-44.
- 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;36:2442-51.
- Vergara D, Simeone P, Bettini S, Tinelli A, Valli L, Storelli C, et al. Antitumor activity of the dietary diterpene carnosol against a panel of human cancer cell lines. Food Funct. 2014;5:1261-9.
- Kar S, Palit S, Ball WB, Das PK. Carnosic acid modulates Akt/IKK/NF-κB signaling by PP2A and induces intrinsic and extrinsic pathway mediated apoptosis in human prostate carcinoma PC-3 cells. Apoptosis. 2012;17:735-47.
- Moran AE, Carothers AM, Weyant MJ, Redston M, Bertagnolli MM. Carnosol inhibits beta-catenin tyrosine phosphorylation and prevents adenoma formation in the C57BL/6J/Min/+ (Min/+) mouse. Cancer Res. 2005;65:1097-104.
- Duran T, Tuncer Z. Investigation of cytotoxic and apoptotic effects of styrax liquidus obtained from Liquidambar orientalis Miller (Hamamelidaceae) on HEp-2 cancer cell with caspase pathway. Eurasian J Med. 2023;55:185-191.
- Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. methods. 2001;25:402-8.
- Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. Ca Cancer J Clin. 2021;71:7-33.
- Hunter AM, LaCasse EC, Korneluk RG. The inhibitors of apoptosis (IAPs) as cancer targets. Apoptosis. 2007;12:1543-68.
- van Engeland M, Nieland LJ, Ramaekers FC, Schutte B, Reutelingsperger CP. Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry. 1998;31:1-9.
- Danilenko M, Wang X, Studzinski GP. Carnosic acid and promotion of monocytic differentiation of HL60-G cells initiated by other agents. J Natl Cancer Inst. 2001;93:1224-33.
- Barni MV, Carlini MJ, Cafferata EG, Puricelli L, Moreno S. Carnosic acid inhibits the proliferation and migration capacity of human colorectal cancer cells. Oncol Rep. 2012;27:1041-8.
- Huang SC, Ho CT, Lin-Shiau SY, Lin JK. Carnosol inhibits the invasion of B16/F10 mouse melanoma cells by suppressing metalloproteinase-9 through down-regulating nuclear factor-kappa B and c-Jun. Biochem Pharmacol. 2005;69:221-32.
- López-Jiménez A, García-Caballero M, Medina MÁ, Quesada AR. Anti-angiogenic properties of carnosol and carnosic acid, two major dietary compounds from rosemary. Eur J Nutr. 2013;52:85-95.
- Park KW, Kundu J, Chae IG, Kim DH, Yu MH, Kundu JK, et al. Carnosol induces apoptosis through generation of ROS and inactivation of STAT3 signaling in human colon cancer HCT116 cells. Int J Oncol. 2014;44:1309-15.
- Jordán MJ, Lax V, Rota MC, Lorán S, Sotomayor JA. Relevance of carnosic acid, carnosol, and rosmarinic acid concentrations in the in vitro antioxidant and antimicrobial activities of Rosmarinus officinalis (L.) methanolic extracts. J Agric Food Chem. 2012;60:9603-8.
- Pérez-Sánchez A, Barrajón-Catalán E, Ruiz-Torres V, Agulló-Chazarra L, Herranz-López M, Valdés A et al. Rosemary (Rosmarinus officinalis) extract causes ROS-induced necrotic cell death and inhibits tumor growth in vivo. Sci Rep. 2019;9:808.
- Jaglanian A, Tsiani E. Rosemary extract inhibits proliferation, survival, Akt, and mTOR signaling in triple-negative breast cancer cells. Int J Mol Sci. 2020;21:810.
- Min KJ, Jung KJ, Kwon TK. Carnosic acid induces apoptosis through reactive oxygen species-mediated Endoplasmic Reticulum stress induction in human renal carcinoma caki cells. J Cancer Prev. 2014;19:170-8.
Carnosol and carnosic acid may be a promising anticancer agent in non-small cell lung cancer treatment
Abstract
Purpose: This study aimed to evaluate the possible anticancer and apoptotic effect of carnosol and carnosic acid on non-small cell lung cancer (NSCLC) cell lines in vitro.
Materials and Methods: Three different NSCLC cell lines (H441, H520, and H661) were used in the study and treatment (carnosol and carnosic acid treatment) and control (no treatment) groups were established in all cell lines. The IC50 doses were determined by MTT method on NSCLC cell lines and the changes in expression levels of apoptosis-related genes (Bax, Bak, caspase-3, p53, c-Myc, Bcl-2, and Bcl-XL) were demonstrated by real-time polymerase chain reaction (qPCR), and apoptosis was confirmed by flow cytometry. The treatment group and control group results were compared.
Results: The IC50 doses of carnosol and carnosic acid were determined; 60 µM for the H441, 20 µM for the H661, 40 µM for the H520, 20 µM for the H441, 40 µM for the H661, 40 µM for the H520, respectively. Carnosol treatment increased Bax, Bak, caspase-3, and p53 expression but decreased Bcl-XL expression in studied lung cancer cell lines. Carnosic acid treatment increased apoptotic Bax, Bak, caspase-3, and p53 expression but decreased antiapoptotic Bcl-2 and Bcl-XL expression (p<0.05).
Conclusion: In this study showed that carnosol and carnosic acid have apoptotic effects on NSCLC cells. With more detailed studies on these agents, these come become a promising agent that can be used in NSCLC cancer treatment in the future.
References
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7-30.
- Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424.
- Ngo SN, Williams DB, Head RJ. Rosemary and cancer prevention: preclinical perspectives. Crit Rev Food Sci Nutr. 2011;51:946-54.
- Moore J, Yousef M, Tsiani E. Anticancer effects of rosemary (Rosmarinus officinalis L.) extract and rosemary extract polyphenols. Nutrients. 2016;8:731.
- 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;65:158-63.
- Johnson JJ. Carnosol: a promising anti-cancer and anti-inflammatory agent. Cancer Lett. 2011;305:1-7.
- Kalantar H, Sadeghi E, Abolnezhadian F, Goudarzi M, Hemmati AA, Basir Z, et al. Carnosol attenuates bleomycin-induced lung damage via suppressing fibrosis, oxidative stress and inflammation in rats. Life Sci. 2021;287:120059.
- Farhadi F, Baradaran Rahimi V, Mohamadi N, Askari VR. Effects of rosmarinic acid, carnosic acid, rosmanol, carnosol, and ursolic acid on the pathogenesis of respiratory diseases. Biofactors. 2023;49:478-501.
- Cattaneo L, Cicconi R, Mignogna G, Giorgi A, Mattei M, Graziani G, et al. Anti-proliferative effect of Rosmarinus officinalis L. extract on human melanoma A375 cells. PLoS One. 2015;10:e0132439.
- Kontogianni VG, Tomic G, Nikolic I, Nerantzaki AA, Sayyad N, Stosic-Grujicic S et al. Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity. Food Chem. 2013;136:120-9.
- Cheung S, Tai J. Anti-proliferative and antioxidant properties of rosemary Rosmarinus officinalis. Oncol Rep. 2007;17:1525-31.
- Xavier CP, Lima CF, Fernandes-Ferreira M, Pereira-Wilson C. Salvia fruticosa, Salvia officinalis, and rosmarinic acid induce apoptosis and inhibit proliferation of human colorectal cell lines: the role in MAPK/ERK pathway. Nutr Cancer. 2009;61:564-71.
- Wei FX, Liu JX, Wang L, Li HZ, Luo JB. Expression of bcl-2 and bax genes in the liver cancer cell line HepG2 after apoptosis induced by essential oils from Rosmarinus officinalis. Zhong Yao Cai. 2008;31:877-9.
- Steiner M, Priel I, Giat J, Levy J, Sharoni Y, Danilenko M. Carnosic acid inhibits proliferation and augments differentiation of human leukemic cells induced by 1,25-dihydroxyvitamin D3 and retinoic acid. Nutr Cancer. 2001;41:135-44.
- 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;36:2442-51.
- Vergara D, Simeone P, Bettini S, Tinelli A, Valli L, Storelli C, et al. Antitumor activity of the dietary diterpene carnosol against a panel of human cancer cell lines. Food Funct. 2014;5:1261-9.
- Kar S, Palit S, Ball WB, Das PK. Carnosic acid modulates Akt/IKK/NF-κB signaling by PP2A and induces intrinsic and extrinsic pathway mediated apoptosis in human prostate carcinoma PC-3 cells. Apoptosis. 2012;17:735-47.
- Moran AE, Carothers AM, Weyant MJ, Redston M, Bertagnolli MM. Carnosol inhibits beta-catenin tyrosine phosphorylation and prevents adenoma formation in the C57BL/6J/Min/+ (Min/+) mouse. Cancer Res. 2005;65:1097-104.
- Duran T, Tuncer Z. Investigation of cytotoxic and apoptotic effects of styrax liquidus obtained from Liquidambar orientalis Miller (Hamamelidaceae) on HEp-2 cancer cell with caspase pathway. Eurasian J Med. 2023;55:185-191.
- Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. methods. 2001;25:402-8.
- Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. Ca Cancer J Clin. 2021;71:7-33.
- Hunter AM, LaCasse EC, Korneluk RG. The inhibitors of apoptosis (IAPs) as cancer targets. Apoptosis. 2007;12:1543-68.
- van Engeland M, Nieland LJ, Ramaekers FC, Schutte B, Reutelingsperger CP. Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry. 1998;31:1-9.
- Danilenko M, Wang X, Studzinski GP. Carnosic acid and promotion of monocytic differentiation of HL60-G cells initiated by other agents. J Natl Cancer Inst. 2001;93:1224-33.
- Barni MV, Carlini MJ, Cafferata EG, Puricelli L, Moreno S. Carnosic acid inhibits the proliferation and migration capacity of human colorectal cancer cells. Oncol Rep. 2012;27:1041-8.
- Huang SC, Ho CT, Lin-Shiau SY, Lin JK. Carnosol inhibits the invasion of B16/F10 mouse melanoma cells by suppressing metalloproteinase-9 through down-regulating nuclear factor-kappa B and c-Jun. Biochem Pharmacol. 2005;69:221-32.
- López-Jiménez A, García-Caballero M, Medina MÁ, Quesada AR. Anti-angiogenic properties of carnosol and carnosic acid, two major dietary compounds from rosemary. Eur J Nutr. 2013;52:85-95.
- Park KW, Kundu J, Chae IG, Kim DH, Yu MH, Kundu JK, et al. Carnosol induces apoptosis through generation of ROS and inactivation of STAT3 signaling in human colon cancer HCT116 cells. Int J Oncol. 2014;44:1309-15.
- Jordán MJ, Lax V, Rota MC, Lorán S, Sotomayor JA. Relevance of carnosic acid, carnosol, and rosmarinic acid concentrations in the in vitro antioxidant and antimicrobial activities of Rosmarinus officinalis (L.) methanolic extracts. J Agric Food Chem. 2012;60:9603-8.
- Pérez-Sánchez A, Barrajón-Catalán E, Ruiz-Torres V, Agulló-Chazarra L, Herranz-López M, Valdés A et al. Rosemary (Rosmarinus officinalis) extract causes ROS-induced necrotic cell death and inhibits tumor growth in vivo. Sci Rep. 2019;9:808.
- Jaglanian A, Tsiani E. Rosemary extract inhibits proliferation, survival, Akt, and mTOR signaling in triple-negative breast cancer cells. Int J Mol Sci. 2020;21:810.
- Min KJ, Jung KJ, Kwon TK. Carnosic acid induces apoptosis through reactive oxygen species-mediated Endoplasmic Reticulum stress induction in human renal carcinoma caki cells. J Cancer Prev. 2014;19:170-8.
There are 32 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Cancer Genetics, Cancer Cell Biology, Molecular Targets |
| Journal Section | Research |
| Authors | |
| Publication Date | March 29, 2024 |
| Submission Date | December 2, 2023 |
| Acceptance Date | February 5, 2024 |
| Published in Issue | Year 2024 Volume: 49 Issue: 1 |
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