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Volume 14, Issue 4 (Jul-Aug 2020)
mljgoums 2020, 14(4): 38-45 |
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khorshid Sofyani E, sharifi R. Synergistic Effect of Docetaxel Combined with Quinacrine on Induction of Apoptosis and Reduction of Cell proliferation in a Lung Cancer Cell Line. mljgoums 2020; 14 (4) :38-45
URL: http://mlj.goums.ac.ir/article-1-1219-en.html
URL: http://mlj.goums.ac.ir/article-1-1219-en.html
1- Department of Biology, Ahar Branch, , e.khorshidi.s@gmail.com
2- Department of Biology, Ahar Branch,
2- Department of Biology, Ahar Branch,
Abstract: (2749 Views)
Background and objectives: Combination chemotherapy with new adjuvants has been introduced as an innovative method of treating various types of cancer. The aim of this study was to investigate potential synergistic effect of quinacrine on the anti-proliferative and anti-apoptotic activity of docetaxel in A549 lung cancer cells.
Methods: Cell viability and apoptosis percentage were evaluated with MTT assay and annexin V staining. To understand the mechanisms through which quinacrine modulates expression of pro-apoptotic and anti-apoptotic genes, expression of Bcl-2, Bcl-xl and Bax genes were investigated using real-time RT-PCR.
Results: The half maximal inhibitory concentration values for docetaxel and quinacrine was 3.16±1.5 nM and 4.4±0.58 μM, respectively. The combination index value of docetaxel and quinacrine was 0.66 against A549 cells, indicating strong synergism. The expression of anti-apoptotic genes Bcl-2 and Bcl-xl reduced significantly, while the expression of the pro-apoptotic gene Bax increased significantly after co-treatment with docetaxel and quinacrine (P<0.05). Treatment of cells with a combination of quinacrine and docetaxel significantly increased the inhibitory effect of docetaxel (reduced proliferation by 50%) and the percentage of apoptotic cells.
Conclusion: Our findings suggest that the combination of quinacrine and docetaxel can be considered as a promising strategy for the treatment of patients with lung cancer.
Methods: Cell viability and apoptosis percentage were evaluated with MTT assay and annexin V staining. To understand the mechanisms through which quinacrine modulates expression of pro-apoptotic and anti-apoptotic genes, expression of Bcl-2, Bcl-xl and Bax genes were investigated using real-time RT-PCR.
Results: The half maximal inhibitory concentration values for docetaxel and quinacrine was 3.16±1.5 nM and 4.4±0.58 μM, respectively. The combination index value of docetaxel and quinacrine was 0.66 against A549 cells, indicating strong synergism. The expression of anti-apoptotic genes Bcl-2 and Bcl-xl reduced significantly, while the expression of the pro-apoptotic gene Bax increased significantly after co-treatment with docetaxel and quinacrine (P<0.05). Treatment of cells with a combination of quinacrine and docetaxel significantly increased the inhibitory effect of docetaxel (reduced proliferation by 50%) and the percentage of apoptotic cells.
Conclusion: Our findings suggest that the combination of quinacrine and docetaxel can be considered as a promising strategy for the treatment of patients with lung cancer.
Research Article: Original Paper |
Subject:
Biochemistry
Received: 2019/05/19 | Accepted: 2019/07/3 | Published: 2020/06/30 | ePublished: 2020/06/30
Received: 2019/05/19 | Accepted: 2019/07/3 | Published: 2020/06/30 | ePublished: 2020/06/30
References
1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015; 136(5): E359-E386. doi: 10.1002/ijc.29210. [DOI:10.1002/ijc.29210] [PubMed] [Google Scholar]
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015; 65(1): 5-29. doi: 10.3322/caac.21254. [DOI:10.3322/caac.21254] [PubMed] [Google Scholar]
3. Silver JK, Baima J. Cancer prehabilitation: an opportunity to decrease treatment-related morbidity, increase cancer treatment options, and improve physical and psychological health outcomes. Am J Phys Med Rehabil. 2013; 92(8): 715-27. doi: 10.1097/PHM.0b013e31829b4afe. [DOI:10.1097/PHM.0b013e31829b4afe] [PubMed] [Google Scholar]
4. Schnipper LE, Davidson NE, Wollins DS, Tyne C, Blayney DW, Blum D, et al. American Society of Clinical Oncology statement: a conceptual framework to assess the value of cancer treatment options. J Clin Oncol. 2015; 33(23): 2563-77. doi: 10.1200/JCO.2015.61.6706. [DOI:10.1200/JCO.2015.61.6706] [PubMed] [Google Scholar]
5. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015; 373(17): 1627-39. doi: 10.1056/NEJMoa1507643. [DOI:10.1056/NEJMoa1507643] [PubMed] [Google Scholar]
6. Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010; 11(2): 121-8. doi: 10.1016/S1470-2045(09)70364-X. [DOI:10.1016/S1470-2045(09)70364-X] [PubMed] [Google Scholar]
7. Herbst RS, Khuri FR. Mode of action of docetaxel-a basis for combination with novel anticancer agents. Cancer Treat Rev. 2003; 29(5): 407-15. DOI: 10.1016/s0305-7372(03)00097-5. [DOI:10.1016/S0305-7372(03)00097-5] [PubMed] [Google Scholar]
8. Baker J, Ajani J, Scotté F, Winther D, Martin M, Aapro MS, et al. Docetaxel-related side effects and their management. Eur J Oncol Nurs. 2008; 12(3): 253-68. doi: 10.1016/j.ejon.2008.03.006. [DOI:10.1016/j.ejon.2008.03.006] [PubMed] [Google Scholar]
9. Ogino S, Meyerhardt JA, Cantor M, Brahmandam M, Clark JW, Namgyal C, et al. Molecular alterations in tumors and response to combination chemotherapy with gefitinib for advanced colorectal cancer. Clin Cancer Res. 2005; 11(18): 6650-6. DOI: 10.1158/1078-0432.CCR-05-0738. [DOI:10.1158/1078-0432.CCR-05-0738] [PubMed] [Google Scholar]
10. Dolcet X, Llobet D, Pallares J, Matias-Guiu X. NF-κB in development and progression of human cancer. Virchows Arch. 2005; 446(5): 475-82. [DOI:10.1007/s00428-005-1264-9] [Google Scholar]
11. Bosman MC, Schuringa JJ, Vellenga E. Constitutive NF-κB activation in AML: Causes and treatment strategies. Crit Rev Oncol Hematol. 2016; 98: 35-44. doi: 10.1016/j.critrevonc.2015.10.001. [DOI:10.1016/j.critrevonc.2015.10.001] [PubMed] [Google Scholar]
12. Taniguchi K, Karin M. NF-κB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol. 2018; 18(5): 309-324. doi: 10.1038/nri.2017.142. [DOI:10.1038/nri.2017.142] [PubMed] [Google Scholar]
13. Zhang J, Wang X, Liu H, Li Z, Chen F, Wang H, Zheng Z, Wang J. TNF‐α enhances apoptosis by promoting chop expression in nucleus pulposus cells: role of the MAPK and NF‐κB pathways. J Orthop Res. 2019; 37(3): 697-705. DOI: 10.1002/jor.24204. [DOI:10.1002/jor.24204] [PubMed] [Google Scholar]
14. Zakaria N, Mohd Yusoff N, Zakaria Z, Widera D, Yahaya BH .Inhibition of NF-κB signaling reduces the stemness characteristics of lung cancer stem cells. Front Oncol. 2018; 8: 166. doi: 10.3389/fonc.2018.00166. [DOI:10.3389/fonc.2018.00166] [PubMed] [Google Scholar]
15. Zeng Y, Zhang Y. MEDICINE, Globularifolin exhibits potent anticancer activity on A549 human lung cancer cell line via induction of mitochondrial apoptosis, cell cycle arrest and NF-kappa B inhibition. Int J Clin Exp Med. 2018; 11(3): 1758-1764. [Google Scholar]
16. Kaur H, Guo H, Eberhart Ch, Raabe E. Targeting the lethal pediatric atypical teratoid/rhabdoid tumors with the DNA minor-groove binding agent quinacrine. AACR Annual Meeting. 2018. [DOI:10.1158/1538-7445.AM2018-4849] [Google Scholar]
17. Mohammadian J, Molavi O, Pirouzpanah M, RahimRahimi A, Samadi N. Stattic enhances the anti-proliferative effect of docetaxel via the Bax/Bcl-2/cyclin B axis in human cancer cells. Process Biochem. 2018; 69: 188-196. DOI: 10.1016/j.procbio.2018.03.004. [DOI:10.1016/j.procbio.2018.03.004] [Google Scholar]
18. Elwakeel A, Soudan H, Eldoksh A, Shalaby M, Eldemellawy M, Ghareeb D, et al. Implementation of the Chou-Talalay method for studying the in vitro pharmacodynamic interactions of binary and ternary drug combinations on MDA-MB-231 triple negative breast cancer cells. Synergy. 20198: 100047. [DOI:10.1016/j.synres.2019.100047] [Google Scholar]
19. Foucquier J, Guedj M. Analysis of drug combinations: current methodological landscape. 2015; 3(3): e00149. [DOI:10.1002/prp2.149] [PubMed] [Google Scholar]
20. Sabzichi M, Ramezani M, Mohammadian J, Ghorbani M, Mardomi A, Najafipour F, et al. The synergistic impact of quinacrine on cell cycle and anti-invasiveness behaviors of doxorubicin in MDA-MB-231 breast cancer cells. Process Biochemistry. 2019; 81: 175-181. [DOI:10.1016/j.procbio.2019.03.007] [Google Scholar]
21. Sabzichi M, Mohammadian J, Mohammadi M, Jahanfar F, Movassagh Pour AA, Hamishehkar H, et al. Vitamin D-Loaded Nanostructured Lipid Carrier (NLC): A New Strategy for Enhancing Efficacy of Doxorubicin in Breast Cancer Treatment. Nutr Cancer. 2017; 69(6): 840-848. doi: 10.1080/01635581.2017.1339820. [DOI:10.1080/01635581.2017.1339820] [PubMed] [Google Scholar]
22. Kawaguchi T, Ando M, Asami K, Okano Y, Fukuda M, Nakagawa H, et al. Randomized phase III trial of erlotinib versus docetaxel as second-or third-line therapy in patients with advanced non-small-cell lung cancer: Docetaxel and Erlotinib Lung Cancer Trial (DELTA). J Clin Oncol. 2014; 32(18): 1902-8. doi: 10.1200/JCO.2013.52.4694. [DOI:10.1200/JCO.2013.52.4694] [PubMed] [Google Scholar]
23. Xu X, Ho W, Zhang X, Bertrand N, Farokhzad O. Cancer nanomedicine: from targeted delivery to combination therapy. Trends Mol Med. 2015; 21(4): 223-232. [DOI:10.1016/j.molmed.2015.01.001] [PubMed] [Google Scholar]
24. Papademetrio DL, Lompardía SL, Simunovich T, Costantino S Mihalez CY, Cavaliere V, et al. Inhibition of survival pathways MAPK and NF-κB triggers apoptosis in pancreatic ductal adenocarcinoma cells via suppression of autophagy. Target Oncol. 2016; 11(2): 183-195. [DOI:10.1007/s11523-015-0388-3] [PubMed] [Google Scholar]
25. Seubwai W, Vaeteewoottacharn K, Kraiklang R, Umezawa K, Okada S, Wongkham S. Inhibition of NF-κB activity enhances sensitivity to anticancer drugs in cholangiocarcinoma cells. Oncol Res. 2016; 23(1-2): 21-8. doi: 10.3727/096504015X14424348426071. [DOI:10.3727/096504015X14424348426071] [PubMed] [Google Scholar]
26. Serasanambati M, Chilakapati sh. Chilakapati, Function of nuclear factor kappa B (NF-κB) in human diseases-a review.biology. 2016; 2(4): 368-387. [DOI:10.22205/sijbs/2016/v2/i4/103443] [Google Scholar]
27. Wei C, Li L, Gupta S. NF-κB-mediated miR-30b regulation in cardiomyocytes cell death by targeting Bcl-2. Mol Cell Biochem. 2014; 387(1-2): 135-141. [DOI:10.1007/s11010-013-1878-1] [PubMed] [Google Scholar]
28. Yuan Z, Jiang H, Zhu X, Liu X, Li J. Ginsenoside Rg3 promotes cytotoxicity of Paclitaxel through inhibiting NF-κB signaling and regulating Bax/Bcl-2 expression on triple-negative breast cancer. Biomed Pharmacother. 2017; 89: 227-232. doi: 10.1016/j.biopha.2017.02.038. [DOI:10.1016/j.biopha.2017.02.038] [PubMed] [Google Scholar]
29. Zhu, S , W. El-Rifai. A combination of suberoylanilide hydroxamic acid and quinacrine is an effective therapeutic approach in preclinical settings of upper gastrointestinal cancers. Cancer Research. 2017; 77(13 Supplement):1095-1095. [DOI:10.1158/1538-7445.AM2017-1095] [Google Scholar]
30. Khurana A, Roy D, Kalogera E, Mondal S, Wen X, He X, Dowdy S, et al. Quinacrine promotes autophagic cell death and chemosensitivity in ovarian cancer and attenuates tumor growth. Oncotarget. 2015; 6(34): 36354. [DOI:10.18632/oncotarget.5632] [PubMed] [Google Scholar]
31. Wang W, Gallant JN, Katz SI, Dolloff NG, Smith CD, Abdulghani J, et al. Quinacrine sensitizes hepatocellular carcinoma cells to TRAIL and chemotherapeutic agents. Cancer Biol Ther. 2011; 12(3): 229-238. [DOI:10.4161/cbt.12.3.17033] [PubMed] [Google Scholar]
32. Ahmad SF, Ansari MA, Zoheir KM, Bakheet SA, Korashy HM, Nadeem A, et al. Regulation of TNF-α and NF-κB activation through the JAK/STAT signaling pathway downstream of histamine 4 receptor in a rat model of LPS-induced joint inflammation. Immunobiology. 2015; 220(7): 889-98. doi: 10.1016/j.imbio.2015.01.008. [DOI:10.1016/j.imbio.2015.01.008] [PubMed] [Google Scholar]
33. Chen GG, Lee JF, Wang SH, Chan UP, Ip PC, Lau WY. Apoptosis induced by activation of peroxisome-proliferator activated receptor-gamma is associated with Bcl-2 and NF-κB in human colon cancer. Life Sci. 2002; 70(22): 2631-2646. [DOI:10.1016/S0024-3205(02)01510-2] [PubMed] [Google Scholar]
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