Öz
This study aimed to investigate the impact of hellebrin on human lung cancer cell (H1299) and breast cancer cell (MCF-7) lines over time. The viability of various concentrations of hellebrin (100 nM-400 nM) on two cancer cell lines was measured using the MTT method. The cellular proliferation over time was examined using xCELLigence real-time cell analysis (RTCA). The results showed a significant decrease in cell viability with increasing concentrations of hellebrin in both cancer cell lines compared to the control group (p˂0.0001). While the viability of both cancer cells decreased after a certain period of hellebrin application, the viability of the control groups increased over time. These findings indicate that hellebrin has high antiproliferative and cytotoxic effects on breast and lung cancer cells. Consequently, this study suggests that hellebrin may have potential as a treatment for other cancers, especially lung cancer, and further in vitro and in vivo experiments are needed to investigate this possibility.
Anahtar Kelimeler
Breast cancer cell Cytotoxicity Hellebrin Lung cancer cell xCELLigence system
Kaynakça
- 1. Torre LA, Siegel RL, Ward EM, Jemal A. Global Cancer Incidence and Mortality Rates and Trends--An Update. Cancer Epidemiol Biomarkers Prev 2016;25(1):16-27.
- 2. Baskar R, Itahana K. Radiation therapy and cancer control in developing countries: Can we save more lives?. Int J Med Sci 2017;14(1):13-17.
- 3. Lortet-Tieulent J, Georges D, Bray F, Vaccarella S. Profiling global cancer incidence and mortality by socioeconomic development. Int J Cancer 2020;147(11):3029-3036.
- 4. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics [published correction appears in CA Cancer J Clin. 2011 Mar-Apr;61(2):134]. CA Cancer J Clin 2011;61(2):69-90.
- 5. Li XX, Wang DQ, Sui CG, Meng FD, Sun SL, Zheng J, et al. Oleandrin induces apoptosis via activating endoplasmic reticulum stress in breast cancer cells. Biomed Pharmacother 2020;124:109852.
- 6. Houghton PJ, Kurmasheva RT. Challenges and Opportunities for Childhood Cancer Drug Development. Pharmacol Rev 2019;71(4):671-697.
- 7. Maior MC, Dobrotă C. Natural compounds with important medical potential found in Helleborus sp. Cent Eur J Biol 2013;8(3):272-285.
- 8. Banuls LMY, Katz A, Miklos W, Cimmino A, Tal DM, Ainbinder E, et al. Hellebrin and its aglycone form hellebrigenin display similar in vitro growth inhibitory effects in cancer cells and binding profiles to the alpha subunits of the Na+/K+-ATPase. Mol Cancer 2013;12:33.
- 9. Gao H, Popescu R, Kopp B, Wang Z. Bufadienolides and their antitumor activity. Nat Prod Rep 2011;28(5):953-969.
- 10. Deng LJ, Li Y, Qi M, Liu JS, Wang S, Hu LJ, et al. Molecular mechanisms of bufadienolides and their novel strategies for cancer treatment. Eur J Pharmacol 2020;887:173379.
- 11. Zhong Y, Zhao C, Wu WY, Fan TY, Li NG, Chen M, et al. Total synthesis, chemical modification and structure-activity relationship of bufadienolides. Eur J Med Chem 2020;189:112038.
- 12. Zhang DM, Liu JS, Deng LJ, Chen MF, Yiu A, Cao HH, et al. Arenobufagin, a natural bufadienolide from toad venom, induces apoptosis and autophagy in human hepatocellular carcinoma cells through inhibition of PI3K/Akt/mTOR pathway. Carcinogenesis 2013;34(6):1331-1342.
- 13. Li H, Cao X, Chen X, Yi X, Xia J, Chen J, et al. Bufadienolides induce apoptosis and autophagy by inhibiting the AKT signaling pathway in melanoma A 375 cells. Mol Med Rep 2019;20(3):2347-2354.
- 14. Chen L, Mai W, Chen M, Hu J, Zhuo Z, Lei X, et al. Arenobufagin inhibits prostate cancer epithelial-mesenchymal transition and metastasis by down-regulating β-catenin. Pharmacol Res 2017;123:130-142.
- 15. Zhao J, Zhang Q, Zou G, Gao G, Yue Q. Arenobufagin, isolated from toad venom, inhibited epithelial-to-mesenchymal transition and suppressed migration and invasion of lung cancer cells via targeting IKKβ/NFκB signal cascade [published correction appears in J Ethnopharmacol 2021 Jan 30;265:113313]. J Ethnopharmacol 2020;250:112492.
- 16. Li W, Pei S, Zhang X, et al. Cinobufotalin inhibits the epithelial-mesenchymal transition of hepatocellular carcinoma cells through down-regulate β-catenin in vitro and in vivo. Eur J Pharmacol 2022;922:174886.
- 17. Banuls LMY, Urban E, Gelbcke M, François D, Kopp B, Kiss R, et al. Structure-activity relationship analysis of bufadienolide-induced in vitro growth inhibitory effects on mouse and human cancer cells. J Nat Prod 2013;76(6):1078-1084.
- 18. CEN-European Committee for Standardization. Biological evaluation of medical devices - Part 5: Tests for Cytotoxicity: In Vitro Methods. 2009c: Standart No. EN ISO 10993-5.
- 19. Şahin Y, Yıldırım E, Yurdakök-Dikmen B, Türk M. The apoptotic and proliferative effects of tulathromycin and gamithromycin on bovine tracheal epithelial cell culture. Turk J Vet Anim Sci 2022;46(1):139-146.
- 20. Florent R, Poulain L, N'Diaye M. Drug Repositioning of the α1-Adrenergic Receptor Antagonist Naftopidil: A Potential New Anti-Cancer Drug?. Int J Mol Sci 2020;21(15):5339.
- 21. Moniri RM, Young A, Reinheimer K, Rayat J, Dai LJ, Warnock GL. Dynamic assessment of cell viability, proliferation and migration using real time cell analyzer system (RTCA). Cytotechnology 2015;67(2):379-386.
- 22. Zhang L, Ye Y, Dhar R, Deng J, Tang H. Estimating Dynamic Cellular Morphological Properties via the Combination of the RTCA System and a Hough-Transform-Based Algorithm. Cells 2019;8(10):1287.
- 23. Peng L, Wang B, Ren P. Reduction of MTT by flavonoids in the absence of cells. Colloids Surf B Biointerfaces 2005;45(2):108-111.
- 24. Lü L, Zhang L, Wai MS, Yew DT, Xu J. Exocytosis of MTT formazan could exacerbate cell injury. Toxicol In Vitro 2012;26(4):636-644.
- 25. Stockert JC, Blázquez-Castro A, Cañete M, Horobin RW, Villanueva A. MTT assay for cell viability: Intracellular localization of the formazan product is in lipid droplets. Acta Histochem 2012;114(8):785-796.
- 26. Stockert JC, Horobin RW, Colombo LL, Blázquez-Castro A. Tetrazolium salts and formazan products in Cell Biology: Viability assessment, fluorescence imaging, and labeling perspectives. Acta Histochem 2018;120(3):159-167.
- 27. Grela E, Kozłowska J, Grabowiecka A. Current methodology of MTT assay in bacteria - A review. Acta Histochem 2018;120(4):303-311.
- 28. Liu Y, Peterson DA, Kimura H, Schubert D. Mechanism of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. J Neurochem 1997;69(2):581-593.
- 29. Yan G, Du Q, Wei X, Miozzi J, Kang C, Wang J, et al. Application of Real-Time Cell Electronic Analysis System in Modern Pharmaceutical Evaluation and Analysis. Molecules 2018;23(12):3280.
- 30. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007;35(4):495-516.
- 31. Han Q, Zhang C, Zhang Y, Li Y, Wu L, Sun X. Bufarenogin induces intrinsic apoptosis via Bax and ANT cooperation. Pharmacol Res Perspect 2021;9(1):e00694.
- 32. Daniel D, Süsal C, Kopp B, Opelz G, Terness P. Apoptosis-mediated selective killing of malignant cells by cardiac steroids: maintenance of cytotoxicity and loss of cardiac activity of chemically modified derivatives. Int Immunopharmacol 2003;3(13-14):1791-1801.
Öz
Bu çalışmada, hellebrinin insan akciğer kanseri hücresi (H1299) ve meme kanseri hücresi (MCF-7) hatları üzerindeki etkisinin zaman içinde araştırılması amaçlanmıştır. Hellebrin'in (100 nM-400 nM) çeşitli konsantrasyonlarının iki kanser hücre hattı üzerindeki canlılığı, MTT yöntemi kullanılarak ölçüldü. Zaman bağlı hücresel çoğalma, xCELLigence gerçek zamanlı hücre analizi (RTCA) kullanılarak incelenmiştir. Sonuçlar, kontrol grubuna kıyasla her iki kanser hücre hattında artan hellebrin konsantrasyonları ile hücre canlılığında önemli bir düşüş gösterdi (p˂0.0001). Belli bir süre hellebrin uygulamasından sonra her iki kanser hücresinin canlılığı azalırken, kontrol gruplarının canlılığı zamanla arttı. Bu bulgular, hellebrin'in meme ve akciğer kanseri hücreleri üzerinde yüksek antiproliferatif ve sitotoksik etkilere sahip olduğunu göstermektedir. Sonuç olarak, bu çalışma hellebrin'in diğer kanserler, özellikle akciğer kanseri için bir tedavi potansiyeline sahip olabileceğini ve bu olasılığı araştırmak için daha fazla in vitro ve in vivo deneylere ihtiyaç olduğunu düşünülmektedir.
Anahtar Kelimeler
Akciğer kanseri hücresi Hellebrin Meme kanseri hücresi Sitotoksisite xCELLigence sistemi
Kaynakça
- 1. Torre LA, Siegel RL, Ward EM, Jemal A. Global Cancer Incidence and Mortality Rates and Trends--An Update. Cancer Epidemiol Biomarkers Prev 2016;25(1):16-27.
- 2. Baskar R, Itahana K. Radiation therapy and cancer control in developing countries: Can we save more lives?. Int J Med Sci 2017;14(1):13-17.
- 3. Lortet-Tieulent J, Georges D, Bray F, Vaccarella S. Profiling global cancer incidence and mortality by socioeconomic development. Int J Cancer 2020;147(11):3029-3036.
- 4. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics [published correction appears in CA Cancer J Clin. 2011 Mar-Apr;61(2):134]. CA Cancer J Clin 2011;61(2):69-90.
- 5. Li XX, Wang DQ, Sui CG, Meng FD, Sun SL, Zheng J, et al. Oleandrin induces apoptosis via activating endoplasmic reticulum stress in breast cancer cells. Biomed Pharmacother 2020;124:109852.
- 6. Houghton PJ, Kurmasheva RT. Challenges and Opportunities for Childhood Cancer Drug Development. Pharmacol Rev 2019;71(4):671-697.
- 7. Maior MC, Dobrotă C. Natural compounds with important medical potential found in Helleborus sp. Cent Eur J Biol 2013;8(3):272-285.
- 8. Banuls LMY, Katz A, Miklos W, Cimmino A, Tal DM, Ainbinder E, et al. Hellebrin and its aglycone form hellebrigenin display similar in vitro growth inhibitory effects in cancer cells and binding profiles to the alpha subunits of the Na+/K+-ATPase. Mol Cancer 2013;12:33.
- 9. Gao H, Popescu R, Kopp B, Wang Z. Bufadienolides and their antitumor activity. Nat Prod Rep 2011;28(5):953-969.
- 10. Deng LJ, Li Y, Qi M, Liu JS, Wang S, Hu LJ, et al. Molecular mechanisms of bufadienolides and their novel strategies for cancer treatment. Eur J Pharmacol 2020;887:173379.
- 11. Zhong Y, Zhao C, Wu WY, Fan TY, Li NG, Chen M, et al. Total synthesis, chemical modification and structure-activity relationship of bufadienolides. Eur J Med Chem 2020;189:112038.
- 12. Zhang DM, Liu JS, Deng LJ, Chen MF, Yiu A, Cao HH, et al. Arenobufagin, a natural bufadienolide from toad venom, induces apoptosis and autophagy in human hepatocellular carcinoma cells through inhibition of PI3K/Akt/mTOR pathway. Carcinogenesis 2013;34(6):1331-1342.
- 13. Li H, Cao X, Chen X, Yi X, Xia J, Chen J, et al. Bufadienolides induce apoptosis and autophagy by inhibiting the AKT signaling pathway in melanoma A 375 cells. Mol Med Rep 2019;20(3):2347-2354.
- 14. Chen L, Mai W, Chen M, Hu J, Zhuo Z, Lei X, et al. Arenobufagin inhibits prostate cancer epithelial-mesenchymal transition and metastasis by down-regulating β-catenin. Pharmacol Res 2017;123:130-142.
- 15. Zhao J, Zhang Q, Zou G, Gao G, Yue Q. Arenobufagin, isolated from toad venom, inhibited epithelial-to-mesenchymal transition and suppressed migration and invasion of lung cancer cells via targeting IKKβ/NFκB signal cascade [published correction appears in J Ethnopharmacol 2021 Jan 30;265:113313]. J Ethnopharmacol 2020;250:112492.
- 16. Li W, Pei S, Zhang X, et al. Cinobufotalin inhibits the epithelial-mesenchymal transition of hepatocellular carcinoma cells through down-regulate β-catenin in vitro and in vivo. Eur J Pharmacol 2022;922:174886.
- 17. Banuls LMY, Urban E, Gelbcke M, François D, Kopp B, Kiss R, et al. Structure-activity relationship analysis of bufadienolide-induced in vitro growth inhibitory effects on mouse and human cancer cells. J Nat Prod 2013;76(6):1078-1084.
- 18. CEN-European Committee for Standardization. Biological evaluation of medical devices - Part 5: Tests for Cytotoxicity: In Vitro Methods. 2009c: Standart No. EN ISO 10993-5.
- 19. Şahin Y, Yıldırım E, Yurdakök-Dikmen B, Türk M. The apoptotic and proliferative effects of tulathromycin and gamithromycin on bovine tracheal epithelial cell culture. Turk J Vet Anim Sci 2022;46(1):139-146.
- 20. Florent R, Poulain L, N'Diaye M. Drug Repositioning of the α1-Adrenergic Receptor Antagonist Naftopidil: A Potential New Anti-Cancer Drug?. Int J Mol Sci 2020;21(15):5339.
- 21. Moniri RM, Young A, Reinheimer K, Rayat J, Dai LJ, Warnock GL. Dynamic assessment of cell viability, proliferation and migration using real time cell analyzer system (RTCA). Cytotechnology 2015;67(2):379-386.
- 22. Zhang L, Ye Y, Dhar R, Deng J, Tang H. Estimating Dynamic Cellular Morphological Properties via the Combination of the RTCA System and a Hough-Transform-Based Algorithm. Cells 2019;8(10):1287.
- 23. Peng L, Wang B, Ren P. Reduction of MTT by flavonoids in the absence of cells. Colloids Surf B Biointerfaces 2005;45(2):108-111.
- 24. Lü L, Zhang L, Wai MS, Yew DT, Xu J. Exocytosis of MTT formazan could exacerbate cell injury. Toxicol In Vitro 2012;26(4):636-644.
- 25. Stockert JC, Blázquez-Castro A, Cañete M, Horobin RW, Villanueva A. MTT assay for cell viability: Intracellular localization of the formazan product is in lipid droplets. Acta Histochem 2012;114(8):785-796.
- 26. Stockert JC, Horobin RW, Colombo LL, Blázquez-Castro A. Tetrazolium salts and formazan products in Cell Biology: Viability assessment, fluorescence imaging, and labeling perspectives. Acta Histochem 2018;120(3):159-167.
- 27. Grela E, Kozłowska J, Grabowiecka A. Current methodology of MTT assay in bacteria - A review. Acta Histochem 2018;120(4):303-311.
- 28. Liu Y, Peterson DA, Kimura H, Schubert D. Mechanism of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. J Neurochem 1997;69(2):581-593.
- 29. Yan G, Du Q, Wei X, Miozzi J, Kang C, Wang J, et al. Application of Real-Time Cell Electronic Analysis System in Modern Pharmaceutical Evaluation and Analysis. Molecules 2018;23(12):3280.
- 30. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007;35(4):495-516.
- 31. Han Q, Zhang C, Zhang Y, Li Y, Wu L, Sun X. Bufarenogin induces intrinsic apoptosis via Bax and ANT cooperation. Pharmacol Res Perspect 2021;9(1):e00694.
- 32. Daniel D, Süsal C, Kopp B, Opelz G, Terness P. Apoptosis-mediated selective killing of malignant cells by cardiac steroids: maintenance of cytotoxicity and loss of cardiac activity of chemically modified derivatives. Int Immunopharmacol 2003;3(13-14):1791-1801.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Veteriner Cerrahi |
| Bölüm | ARAŞTIRMA MAKALESİ |
| Yazarlar | |
| Erken Görünüm Tarihi | 14 Haziran 2023 |
| Yayımlanma Tarihi | 15 Haziran 2023 |
| Gönderilme Tarihi | 21 Şubat 2023 |
| Kabul Tarihi | 22 Mayıs 2023 |
| Yayımlandığı Sayı | Yıl 2023 Cilt: 94 Sayı: 2 |
Veteriner Hekimler Derneği Dergisi açık erişimli bir dergi olup, derginin yayın modeli Budapeşte Erişim Girişimi (BOAI) bildirisine dayanmaktadır. Yayınlanan tüm içerik, çevrimiçi ve ücretsiz olarak sunulan Creative Commons CC BY-NC 4.0 lisansı altında lisanslanmıştır. Yazarlar, Veteriner Hekimler Derneği Dergisi'nde yayınlanan eserlerinin telif haklarını saklı tutarlar.
Veteriner Hekimler Derneği / Turkish Veterinary Medical Society