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The cytotoxic and antioxidant effects of sorafenib and osage orange extract combination in A549 cell lines

Year 2024, Volume: 7 Issue: 2, 151 - 156, 31.12.2024
https://doi.org/10.46239/ejbcs.1560686

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. Developing new therapeutic strategies that are effective, safe, and specific for lung cancer cells is a priority in cancer research. This study investigates the cytotoxic and antioxidant effects of a combination of sorafenib and Maclura pomifera extract, known as Osage orange, in A549 human lung cancer cell lines. Sorafenib, a multikinase inhibitor, has shown promising results in the treatment of various types of cancer. However, its therapeutic potential remains limited due to side effects and resistance developed by cancer cells. Natural extracts, especially those obtained from plants such as Osage orange, show significant antioxidant properties and may improve the efficacy and reduce the toxicity of conventional chemotherapy drugs. A549 human lung cancer cell lines were treated with various concentrations of sorafenib, Osage orange extract, and their combination. Cell viability was evaluated by MTT assay, while the levels of total oxidant status (TOS) and total antioxidant status (TAS) were measured. The combination of sorafenib and Osage orange extract demonstrated a significant decrease in cell viability compared to sorafenib treatment alone. In addition, the combination treatment significantly reduced total oxidant levels, indicating increased antioxidant activity. The findings of this study demonstrate that the combination of sorafenib and Osage orange extract exhibits potent cytotoxic and antioxidant effects in A549 human lung cancer cell lines. This combination therapy has the potential to be a more effective and safer alternative in the treatment of lung cancer, but further in vivo studies and clinical trials are required.

References

  • Abd-Elbaset M, Mansour AM, Ahmed OM, Abo-Youssef AM. 2020. The potential chemotherapeutic effect of β-ionone and/ or sorafenib against hepatocellular carcinoma via its antioxidant effect, PPAR-γ, FOXO-1, Ki-67, Bax, and Bcl-2 signaling pathways. Naunyn Schmiedebergs Arch. 393:1611-1624
  • Barnes RA, Gerber NN. 1955. The Antifungal Agent from Osage Orange Wood. J Am Chem.Soc. 77(12):3259-3262
  • Cabral LKD, Tiribelli C, Sukowati CHC. 2020. Sorafenib resistance in hepatocellular carcinoma: The relevance of genetic heterogeneity. Cancers (Basel). 12(6):1576
  • Chan YT, Wu J, Lu Y, Li Q, Feng Z, Xu L, Yuan H, Xing T, Zhang C, Tan HY, Feng Y, Wang N. 2024. Loss of lncRNA LINC01056 leads to sorafenib resistance in HCC. Mol Cancer. 23:74
  • Dal Lago L, D’Hondt V, Awada A. 2008. Selected combination therapy with sorafenib: A review of clinical data and perspectives in advanced solid tumors. Oncologist. 13(8):845-858
  • El-Hamawi O, Eldin ZE, Abdel-Moneim A, Zanaty MI, El-Shahawy AA. 2023. A nanoformula comprising three entities in one design: Synthetic Sorafenib-loaded poly(lactic-co-glycolic acid) conjugated with natural curcumin induces a distinct intrinsic apoptosis pathway versus non-small cell lung cancer A549 cell lines. https://www.researchsquare.com/article/rs-2824510/v1. Accessed 21 Sept 2024.
  • Filip S, Djarmati Z, Lisichkov K, Csanadi J, Jankov RM. 2015. Isolation and characterization of Maclura (Maclura pomifera) extracts obtained by supercritical fluid extraction. Industrial Crops and Products. 76:995-1000
  • Filip S, Đurović S, Blagojević S, Tomić A, Ranitović A, Gašić U, Zeković Z. 2021. Chemical composition and antimicrobial activity of Osage orange (Maclura pomifera) leaf extracts. Arch Pharm. 354(2):2000195
  • Hu B, Sun D, Sun C, Sun Y, Sun H, Zhu Q, Yang X, Gao Y, Tang W, Fan J, Maitra A, Anders R, Xu Y. 2015. A polymeric nanoparticle formulation of curcumin in combination with sorafenib synergistically inhibits tumor growth and metastasis in an orthotopic model of human hepatocellular carcinoma. Biochem Biophys Res Commun. 468(4): 525-532
  • Huang KY, Wang TH, Chen CC, Leu YL, Li HJ, Jhong CL, Chen CY. 2021. Growth suppression in lung cancer cells harboring EGFR-C797S mutation by quercetin. Biomolecules. 11(9):1271
  • Hussain Y, Singh J, Meena A, Sinha RA, Luqman S. 2023. Escin enhanced the efficacy of sorafenib by autophagy-mediated apoptosis in lung cancer cells. Phytother Res. 37(10):4819-4837
  • Jane EP, Premkumar DR, Pollack IF. 2006. Coadministration of sorafenib with rottlerin potently inhibits cell proliferation and migration in human malignant glioma cells. J Pharmacol Exp Ther. 319(3):1070-1080
  • Jiang S, Wang Q, Feng M, Li J, Guan Z, An D, Dong M, Peng Y, Kuerban K, Ye L. 2017. C2-ceramide enhances sorafenib-induced caspase-dependent apoptosis via PI3K/AKT/mTOR and Erk signaling pathways in HCC cells. Appl Microbiol Biotechnol. 101(4):1535-1546
  • Kuo JY, Liao CL, Ma YS, Kuo CL, Chen JC, Huang YP, Chung JG. 2022. Combination treatment of sorafenib and bufalin induces apoptosis in NCI-H292 human lung cancer cells in vitro. In Vivo. 36(2):582-595
  • Kupeli E, Orhan I, Toker G, Yesilada E. 2006. Anti-inflammatory and antinociceptive potential of Maclura pomifera (Rafin.) Schneider fruit extracts and its major isoflavonoids, scandenone and auriculasin. J Ethnopharmacol. 107(2):169-174
  • Lakornwong W, Kanokmedhakul K, Masranoi J, Tontapha S, Yahuafai J, Laphookhieo S, Kanokmedhakul S. 2022. Cytotoxic and antibacterial xanthones from the roots of Maclura cochinchinensis. Nat Prod Res. 36(23): 6021-6030
  • Li J, Pan YY, Zhang Y. 2013. Synergistic interaction between sorafenib and gemcitabine in EGFR-TKI-sensitive and EGFR-TKI-resistant human lung cancer cell lines. Oncol Lett. 5(2):440-446
  • Li Y, Yan H, Xu X, Liu H, Wu C, Zhao L. 2020. Erastin/sorafenib induces cisplatin resistant non-small cell lung cancer cell ferroptosis through inhibition of the Nrf2/xCT pathway. Oncol Lett. 19(1):323-333
  • Mukherjee AK, Basu S, Sarkar N, Ghosh AC. 2001. Advances in cancer therapy with plant-based natural products. Curr Med Chem. 8(12):1467-1486
  • Singh, AK, Hennon M, Ma SJ, Demmy TL, Picone A, Dexter EU, Nwogu C, Attwood K, Tan W, Hermann GM, Fung-Kee-Fung S, Malhotra HK, Yendamuri S, Gomez-Suescun, JA. 2018. A pilot study of stereotactic body radiation therapy (SBRT) after surgery for stage III non-small cell lung cancer. BMC Cancer. 18:1183
  • Singh D, Khan MA, Akhtar K, Arjmand F, Siddique HR. 2022. Apigenin alleviates cancer drug sorafenib-induced multiple toxic effects in Swiss albino mice via anti-oxidative stress. Toxicol Appl Pharmacol. 447:116072
  • Smith JL, Perino JV. 1981. Osage orange (Maclura pomifera): History and economic uses. Econ Bot. 35(1):24-41
  • Smit EF, Dingemans AMC, Thunnissen FB, Hochstenbach MM, van Suylen RJ, Postmus PE. 2010. Sorafenib in patients with advanced non-small cell lung cancer that harbor K-ras mutations: a brief report. J Thorac Oncol. 5(5): 719-720
  • Solowey E, Lichtenstein M, Sallon S, Paavilainen H, Solowey E, Lorberboum-Galski H. 2014. Evaluating medicinal plants for anticancer activity. Sci World J. 2014(1): 721402.
  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. 2021. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71(3):209-249
  • Tang W, Chen Z, Zhang W, Cheng Y, Zhang B, Wu F, Wang Q, Wang S, Rong D, Reiter FP, De Toni EN, Wang X. 2020. The mechanisms of sorafenib resistance in hepatocellular carcinoma: theoretical basis and therapeutic aspects. Signal Transduct Target Ther. 5(1):87
  • Thandra KC, Barsouk A, Saginala K, Aluru JS, Barsouk A. 2021. Epidemiology of lung cancer. Contemp Oncol/ Współcz Onkol. 25(1):45-52
  • Zhang Y, Zhang B, Zhang A, Zhao Y, Zhao J, Liu J, Rao Z. 2012. Synergistic growth inhibition by sorafenib and vitamin K2 in human hepatocellular carcinoma cells. Clin. 67:1093-1099
  • Zhang J, Chen YL, Ji G, Fang W, Gao Z, Liu Y, Gao F. 2013. Sorafenib inhibits epithelial-mesenchymal transition through an epigenetic-based mechanism in human lung epithelial cells. PLoS One. 8(5):e64954.
  • Zhao J, Lin E, Bai Z, Jia Y, Wang B, Dai Y, ZhuoW, Zeng G, Liu X, Cai C, Li P, Zou B Li J. (2023). Cancer-associated fibroblasts induce sorafenib resistance of hepatocellular carcinoma cells through CXCL12/FOLR1. BMC Cancer. 23(1): 1198.
  • Zheng M. 2016. Classification and pathology of lung cancer. Surg Oncol Clin. 25(3):447-468.

Sorafenib ve Yalancı portakal ekstresi kombinasyonunun A549 hücre hatları üzerindeki in vitro sitotoksik ve antioksidan aktivitesi

Year 2024, Volume: 7 Issue: 2, 151 - 156, 31.12.2024
https://doi.org/10.46239/ejbcs.1560686

Abstract

Akciğer kanseri, dünya genelinde kansere bağlı ölümlerin önde gelen nedenidir. Özellikle akciğer kanseri hücrelerine özgü, etkili ve güvenli yeni terapötik stratejilerin geliştirilmesi kanser araştırmalarında bir önceliktir. Bu çalışma, A549 insan akciğer kanseri hücre hatlarında sorafenib ve Yalancı portakal olarak bilinen Maclura pomifera ekstresi kombinasyonunun sitotoksik ve antioksidan etkilerini araştırmaktadır. Bir multikinaz inhibitörü olan sorafenib, çeşitli kanser türlerinin tedavisinde umut verici sonuçlar göstermiştir. Ancak, kanser hücreleri tarafından geliştirilen direnç ve yan etkiler nedeniyle terapötik potansiyeli sınırlı kalmaktadır. Özellikle Yalancı portakal gibi bitkilerden elde edilen doğal özler, önemli antioksidan özellik gösterir ve geleneksel kemoterapi ilaçlarının etkinliğini artırıp toksisitesini azaltabilir. A549 insan akciğer kanseri hücre hatları sorafenib, Yalancı portakal ekstresi ve bunların kombinasyonunun çeşitli konsantrasyonları ile muamele edilmiştir. Hücre canlılığı MTT testi ile değerlendirilirken, toplam oksidan durumu (TOS) ve toplam antioksidan durumu (TAS) seviyeleri ölçülmüştür. Sorafenib ve Yalancı portakal ekstresi kombinasyonu, tek başına sorafenib tedavisine kıyasla hücre canlılığında önemli bir azalma göstermiştir. Ayrıca, kombinasyon tedavisi toplam oksidan seviyelerinde önemli bir düşüşe yol açarak antioksidan aktivitenin arttığını göstermiştir. Bu çalışmanın bulguları, sorafenib ve Yalancı portakal ekstresi kombinasyonunun A549 insan akciğer kanseri hücre hatlarında güçlü sitotoksik ve antioksidan etkiler sergilediğini göstermektedir. Bu kombinasyon tedavisi, akciğer kanseri tedavisinde daha etkili ve daha güvenli bir alternatif olma potansiyeline sahiptir ve daha ileri in vivo çalışmalar ve klinik denemeler gerektirmektedir.

References

  • Abd-Elbaset M, Mansour AM, Ahmed OM, Abo-Youssef AM. 2020. The potential chemotherapeutic effect of β-ionone and/ or sorafenib against hepatocellular carcinoma via its antioxidant effect, PPAR-γ, FOXO-1, Ki-67, Bax, and Bcl-2 signaling pathways. Naunyn Schmiedebergs Arch. 393:1611-1624
  • Barnes RA, Gerber NN. 1955. The Antifungal Agent from Osage Orange Wood. J Am Chem.Soc. 77(12):3259-3262
  • Cabral LKD, Tiribelli C, Sukowati CHC. 2020. Sorafenib resistance in hepatocellular carcinoma: The relevance of genetic heterogeneity. Cancers (Basel). 12(6):1576
  • Chan YT, Wu J, Lu Y, Li Q, Feng Z, Xu L, Yuan H, Xing T, Zhang C, Tan HY, Feng Y, Wang N. 2024. Loss of lncRNA LINC01056 leads to sorafenib resistance in HCC. Mol Cancer. 23:74
  • Dal Lago L, D’Hondt V, Awada A. 2008. Selected combination therapy with sorafenib: A review of clinical data and perspectives in advanced solid tumors. Oncologist. 13(8):845-858
  • El-Hamawi O, Eldin ZE, Abdel-Moneim A, Zanaty MI, El-Shahawy AA. 2023. A nanoformula comprising three entities in one design: Synthetic Sorafenib-loaded poly(lactic-co-glycolic acid) conjugated with natural curcumin induces a distinct intrinsic apoptosis pathway versus non-small cell lung cancer A549 cell lines. https://www.researchsquare.com/article/rs-2824510/v1. Accessed 21 Sept 2024.
  • Filip S, Djarmati Z, Lisichkov K, Csanadi J, Jankov RM. 2015. Isolation and characterization of Maclura (Maclura pomifera) extracts obtained by supercritical fluid extraction. Industrial Crops and Products. 76:995-1000
  • Filip S, Đurović S, Blagojević S, Tomić A, Ranitović A, Gašić U, Zeković Z. 2021. Chemical composition and antimicrobial activity of Osage orange (Maclura pomifera) leaf extracts. Arch Pharm. 354(2):2000195
  • Hu B, Sun D, Sun C, Sun Y, Sun H, Zhu Q, Yang X, Gao Y, Tang W, Fan J, Maitra A, Anders R, Xu Y. 2015. A polymeric nanoparticle formulation of curcumin in combination with sorafenib synergistically inhibits tumor growth and metastasis in an orthotopic model of human hepatocellular carcinoma. Biochem Biophys Res Commun. 468(4): 525-532
  • Huang KY, Wang TH, Chen CC, Leu YL, Li HJ, Jhong CL, Chen CY. 2021. Growth suppression in lung cancer cells harboring EGFR-C797S mutation by quercetin. Biomolecules. 11(9):1271
  • Hussain Y, Singh J, Meena A, Sinha RA, Luqman S. 2023. Escin enhanced the efficacy of sorafenib by autophagy-mediated apoptosis in lung cancer cells. Phytother Res. 37(10):4819-4837
  • Jane EP, Premkumar DR, Pollack IF. 2006. Coadministration of sorafenib with rottlerin potently inhibits cell proliferation and migration in human malignant glioma cells. J Pharmacol Exp Ther. 319(3):1070-1080
  • Jiang S, Wang Q, Feng M, Li J, Guan Z, An D, Dong M, Peng Y, Kuerban K, Ye L. 2017. C2-ceramide enhances sorafenib-induced caspase-dependent apoptosis via PI3K/AKT/mTOR and Erk signaling pathways in HCC cells. Appl Microbiol Biotechnol. 101(4):1535-1546
  • Kuo JY, Liao CL, Ma YS, Kuo CL, Chen JC, Huang YP, Chung JG. 2022. Combination treatment of sorafenib and bufalin induces apoptosis in NCI-H292 human lung cancer cells in vitro. In Vivo. 36(2):582-595
  • Kupeli E, Orhan I, Toker G, Yesilada E. 2006. Anti-inflammatory and antinociceptive potential of Maclura pomifera (Rafin.) Schneider fruit extracts and its major isoflavonoids, scandenone and auriculasin. J Ethnopharmacol. 107(2):169-174
  • Lakornwong W, Kanokmedhakul K, Masranoi J, Tontapha S, Yahuafai J, Laphookhieo S, Kanokmedhakul S. 2022. Cytotoxic and antibacterial xanthones from the roots of Maclura cochinchinensis. Nat Prod Res. 36(23): 6021-6030
  • Li J, Pan YY, Zhang Y. 2013. Synergistic interaction between sorafenib and gemcitabine in EGFR-TKI-sensitive and EGFR-TKI-resistant human lung cancer cell lines. Oncol Lett. 5(2):440-446
  • Li Y, Yan H, Xu X, Liu H, Wu C, Zhao L. 2020. Erastin/sorafenib induces cisplatin resistant non-small cell lung cancer cell ferroptosis through inhibition of the Nrf2/xCT pathway. Oncol Lett. 19(1):323-333
  • Mukherjee AK, Basu S, Sarkar N, Ghosh AC. 2001. Advances in cancer therapy with plant-based natural products. Curr Med Chem. 8(12):1467-1486
  • Singh, AK, Hennon M, Ma SJ, Demmy TL, Picone A, Dexter EU, Nwogu C, Attwood K, Tan W, Hermann GM, Fung-Kee-Fung S, Malhotra HK, Yendamuri S, Gomez-Suescun, JA. 2018. A pilot study of stereotactic body radiation therapy (SBRT) after surgery for stage III non-small cell lung cancer. BMC Cancer. 18:1183
  • Singh D, Khan MA, Akhtar K, Arjmand F, Siddique HR. 2022. Apigenin alleviates cancer drug sorafenib-induced multiple toxic effects in Swiss albino mice via anti-oxidative stress. Toxicol Appl Pharmacol. 447:116072
  • Smith JL, Perino JV. 1981. Osage orange (Maclura pomifera): History and economic uses. Econ Bot. 35(1):24-41
  • Smit EF, Dingemans AMC, Thunnissen FB, Hochstenbach MM, van Suylen RJ, Postmus PE. 2010. Sorafenib in patients with advanced non-small cell lung cancer that harbor K-ras mutations: a brief report. J Thorac Oncol. 5(5): 719-720
  • Solowey E, Lichtenstein M, Sallon S, Paavilainen H, Solowey E, Lorberboum-Galski H. 2014. Evaluating medicinal plants for anticancer activity. Sci World J. 2014(1): 721402.
  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. 2021. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71(3):209-249
  • Tang W, Chen Z, Zhang W, Cheng Y, Zhang B, Wu F, Wang Q, Wang S, Rong D, Reiter FP, De Toni EN, Wang X. 2020. The mechanisms of sorafenib resistance in hepatocellular carcinoma: theoretical basis and therapeutic aspects. Signal Transduct Target Ther. 5(1):87
  • Thandra KC, Barsouk A, Saginala K, Aluru JS, Barsouk A. 2021. Epidemiology of lung cancer. Contemp Oncol/ Współcz Onkol. 25(1):45-52
  • Zhang Y, Zhang B, Zhang A, Zhao Y, Zhao J, Liu J, Rao Z. 2012. Synergistic growth inhibition by sorafenib and vitamin K2 in human hepatocellular carcinoma cells. Clin. 67:1093-1099
  • Zhang J, Chen YL, Ji G, Fang W, Gao Z, Liu Y, Gao F. 2013. Sorafenib inhibits epithelial-mesenchymal transition through an epigenetic-based mechanism in human lung epithelial cells. PLoS One. 8(5):e64954.
  • Zhao J, Lin E, Bai Z, Jia Y, Wang B, Dai Y, ZhuoW, Zeng G, Liu X, Cai C, Li P, Zou B Li J. (2023). Cancer-associated fibroblasts induce sorafenib resistance of hepatocellular carcinoma cells through CXCL12/FOLR1. BMC Cancer. 23(1): 1198.
  • Zheng M. 2016. Classification and pathology of lung cancer. Surg Oncol Clin. 25(3):447-468.
There are 31 citations in total.

Details

Primary Language Turkish
Subjects Cell Development, Proliferation and Death
Journal Section Research Articles
Authors

Deniz Altun Çolak 0000-0002-3576-0355

Heval Kaya

Tuğba Atıcı 0000-0002-4798-935X

Early Pub Date December 27, 2024
Publication Date December 31, 2024
Submission Date October 3, 2024
Acceptance Date November 28, 2024
Published in Issue Year 2024 Volume: 7 Issue: 2

Cite

APA Altun Çolak, D., Kaya, H., & Atıcı, T. (2024). Sorafenib ve Yalancı portakal ekstresi kombinasyonunun A549 hücre hatları üzerindeki in vitro sitotoksik ve antioksidan aktivitesi. Eurasian Journal of Biological and Chemical Sciences, 7(2), 151-156. https://doi.org/10.46239/ejbcs.1560686
AMA Altun Çolak D, Kaya H, Atıcı T. Sorafenib ve Yalancı portakal ekstresi kombinasyonunun A549 hücre hatları üzerindeki in vitro sitotoksik ve antioksidan aktivitesi. Eurasian J. Bio. Chem. Sci. December 2024;7(2):151-156. doi:10.46239/ejbcs.1560686
Chicago Altun Çolak, Deniz, Heval Kaya, and Tuğba Atıcı. “Sorafenib Ve Yalancı Portakal Ekstresi Kombinasyonunun A549 hücre Hatları üzerindeki in Vitro Sitotoksik Ve Antioksidan Aktivitesi”. Eurasian Journal of Biological and Chemical Sciences 7, no. 2 (December 2024): 151-56. https://doi.org/10.46239/ejbcs.1560686.
EndNote Altun Çolak D, Kaya H, Atıcı T (December 1, 2024) Sorafenib ve Yalancı portakal ekstresi kombinasyonunun A549 hücre hatları üzerindeki in vitro sitotoksik ve antioksidan aktivitesi. Eurasian Journal of Biological and Chemical Sciences 7 2 151–156.
IEEE D. Altun Çolak, H. Kaya, and T. Atıcı, “Sorafenib ve Yalancı portakal ekstresi kombinasyonunun A549 hücre hatları üzerindeki in vitro sitotoksik ve antioksidan aktivitesi”, Eurasian J. Bio. Chem. Sci., vol. 7, no. 2, pp. 151–156, 2024, doi: 10.46239/ejbcs.1560686.
ISNAD Altun Çolak, Deniz et al. “Sorafenib Ve Yalancı Portakal Ekstresi Kombinasyonunun A549 hücre Hatları üzerindeki in Vitro Sitotoksik Ve Antioksidan Aktivitesi”. Eurasian Journal of Biological and Chemical Sciences 7/2 (December 2024), 151-156. https://doi.org/10.46239/ejbcs.1560686.
JAMA Altun Çolak D, Kaya H, Atıcı T. Sorafenib ve Yalancı portakal ekstresi kombinasyonunun A549 hücre hatları üzerindeki in vitro sitotoksik ve antioksidan aktivitesi. Eurasian J. Bio. Chem. Sci. 2024;7:151–156.
MLA Altun Çolak, Deniz et al. “Sorafenib Ve Yalancı Portakal Ekstresi Kombinasyonunun A549 hücre Hatları üzerindeki in Vitro Sitotoksik Ve Antioksidan Aktivitesi”. Eurasian Journal of Biological and Chemical Sciences, vol. 7, no. 2, 2024, pp. 151-6, doi:10.46239/ejbcs.1560686.
Vancouver Altun Çolak D, Kaya H, Atıcı T. Sorafenib ve Yalancı portakal ekstresi kombinasyonunun A549 hücre hatları üzerindeki in vitro sitotoksik ve antioksidan aktivitesi. Eurasian J. Bio. Chem. Sci. 2024;7(2):151-6.