سامانه مدیریت نشریات علمی دانشگاه علوم پزشکی مشهد

Ahmad, Irfan, Irfan, Safia, Masroor Ali Beg, Mirza, Kamli, Hosam, Ali, Syed Parveen, Begum, Naseem, Alshahrani, . Mohammad, Rajagopalan, Prasanna. (1400). The SMAC mimetic AT-101 exhibits anti-tumor and anti-metastasis activity in lung adenocarcinoma cells by the IAPs/ caspase-dependent apoptosis and p65-NFƙB cross-talk. , 24(7), 969-977. doi: 10.22038/ijbms.2021.56400.12586
Irfan Ahmad; Safia Irfan; Mirza Masroor Ali Beg; Hosam Kamli; Syed Parveen Ali; Naseem Begum; . Mohammad Y Alshahrani; Prasanna Rajagopalan. "The SMAC mimetic AT-101 exhibits anti-tumor and anti-metastasis activity in lung adenocarcinoma cells by the IAPs/ caspase-dependent apoptosis and p65-NFƙB cross-talk". , 24, 7, 1400, 969-977. doi: 10.22038/ijbms.2021.56400.12586
Ahmad, Irfan, Irfan, Safia, Masroor Ali Beg, Mirza, Kamli, Hosam, Ali, Syed Parveen, Begum, Naseem, Alshahrani, . Mohammad, Rajagopalan, Prasanna. (1400). 'The SMAC mimetic AT-101 exhibits anti-tumor and anti-metastasis activity in lung adenocarcinoma cells by the IAPs/ caspase-dependent apoptosis and p65-NFƙB cross-talk', , 24(7), pp. 969-977. doi: 10.22038/ijbms.2021.56400.12586
Ahmad, Irfan, Irfan, Safia, Masroor Ali Beg, Mirza, Kamli, Hosam, Ali, Syed Parveen, Begum, Naseem, Alshahrani, . Mohammad, Rajagopalan, Prasanna. The SMAC mimetic AT-101 exhibits anti-tumor and anti-metastasis activity in lung adenocarcinoma cells by the IAPs/ caspase-dependent apoptosis and p65-NFƙB cross-talk. , 1400; 24(7): 969-977. doi: 10.22038/ijbms.2021.56400.12586

The SMAC mimetic AT-101 exhibits anti-tumor and anti-metastasis activity in lung adenocarcinoma cells by the IAPs/ caspase-dependent apoptosis and p65-NFƙB cross-talk

Iranian Journal of Basic Medical Sciences
مقاله 14، دوره 24، شماره 7، مهر 2021، صفحه 969-977    اصل مقاله (854.94 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2021.56400.12586
نویسندگان
Irfan Ahmad1؛ Safia Irfan2؛ Mirza Masroor Ali Beg3، 4، 5؛ Hosam Kamli1؛ Syed Parveen Ali6؛ Naseem Begum1؛ . Mohammad Y Alshahrani1؛ Prasanna Rajagopalan* 1، 7
1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
2Department of Physiology, College of Medicine, King Khalid University, Abha, Saudi Arabia
3Department of Biochemistry, Maulana Azad Medical College, New Delhi, India
4Faculty of Medicine, Ala-Too International University, Bishkek, Kyrgyzstan
5Centre for Promotion of Medical Research, Ala-Too International University, Bishkek, Kyrgyzstan
6Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
7Central Research Laboratory, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
چکیده
Objective(s): The Inhibitors of Apoptosis (IAPs) regulate initiator and effector phases of caspase mediated apoptosis. This study evaluates the effects of SMAC mimetic AT-101 in regulation of IAPs/caspases/NFƙB-p65 in an adenocarcinoma cell line.
Materials and Methods: MTT assay was performed in the NCI-H522 cell line. Flow cytometry was used for detecting cell cycle, apoptosis, and NFƙB-p65 regulation.  Effects of AT-101 on IAPs and caspases were determined by quantitative real time-PCR and western blotting. AutoDock-VINA was used for computational analysis.    
Results: AT-101 reduced the cell proliferation of NCI-H522 with a GI50 value of 7 μM. The compound arrested adenocarcinoma cells in the G1 phase of the cell cycle and increased early and late phase apoptosis while decreasing tumor-cell trans-migration. AT-101 treatment to NCI H522 at a concentration of 0.35 μM decreased XIAP, cIAP-1, and cIAP-2 mRNA levels to 4.39±0.66, 1.93±0.26, and 2.20±0.24 folds, respectively. Increased dose of AT-101 at 0.7 μM concentration further decreased XIAP, cIAP-1, and cIAP-2 mRNA levels to 2.44±0.67, 1.46±0.93, and 0.97±0.10 folds, respectively.  Similar effects of a dose-dependent decrease in the protein expressions of XIAP, cIAP-1, and cIAP-2 were observed with AT-101 treatments, while a dose-responsive increase in the mRNA and protein expression levels of caspase 6 and caspase 7 was observed in the NCI-H522 cell line. The compound exhibited binding affinity (-6.1 kcal/mol) and inhibited NFƙB-p65 in these cells.
Conclusion: AT-101 had anti-tumor efficacy against lung adenocarcinoma cells which could be mediated through IAPs/caspase-dependent apoptosis and NFƙB-p65 cross talk. Results from this study suggests a signal cross talk between IAPs and NFkB and open new channels for further investigations in therapeutic intervention against lung cancer management.
کلیدواژه‌ها
AT-101؛ Caspases؛ IAPs؛ NCI-H522؛ NFƙB؛ SMAC mimetic
مراجع
1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013; 63:11-30.
2. Chen PL, Zhao T, Feng R, Chai J, Tong GX, Wang DB. Patterns and trends with cancer incidence and mortality rates reported by the China National Cancer Registry. Asian Pac J Cancer Prev 2014; 15:6327-6332.
3. Kroemer G, Levine B. Autophagic cell death: the story of a misnomer. Nat Rev Mol Cell Biol 2008; 9:1004-1010.
4. Tsujimoto Y, Shimizu S. Another way to die: autophagic programmed cell death. Cell Death Differ 2005; 12 Suppl 2:1528-1534.
5. Eckelman BP, Salvesen GS, Scott FL. Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family. EMBO Rep 2006; 7:988-994.
6. Scott FL, Denault JB, Riedl SJ, Shin H, Renatus M, Salvesen GS. XIAP inhibits caspase-3 and -7 using two binding sites: evolutionarily conserved mechanism of IAPs. Embo J 2005; 24:645-655.
7. Obexer P, Ausserlechner MJ. X-Linked inhibitor of apoptosis protein – a critical death resistance regulator and therapeutic target for personalized cancer therapy.  Front Oncol 2014; 4:197-205.
8. Kim JY, Morgan M, Kim DG, Lee JY, Bai L, Lin Y, et al. TNFα induced noncanonical NF-κB activation is attenuated by RIP1 through stabilization of TRAF2. J Cell Sci 2011; 124:647-656.
9. Vince JE, Pantaki D, Feltham R, Mace PD, Cordier SM, Schmukle AC, et al. TRAF2 must bind to cellular inhibitors of apoptosis for tumor necrosis factor (tnf) to efficiently activate nf-{kappa}b and to prevent tnf-induced apoptosis. J Biol Chem 2009; 284:35906-35915.
10. Mansouri A, Zhang Q, Ridgway LD, Tian L, Claret FX. Cisplatin resistance in an ovarian carcinoma is associated with a defect in programmed cell death control through XIAP regulation. Oncol Res 2003; 13:399-404.
11. Tamm I, Kornblau SM, Segall H, Krajewski S, Welsh K, Kitada S, et al. Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res 2000; 6:1796-1803.
12. Akyurek N, Ren Y, Rassidakis GZ, Schlette EJ, Medeiros LJ. Expression of inhibitor of apoptosis proteins in B-cell non-Hodgkin and Hodgkin lymphomas. Cancer 2006; 107:1844-1851.
13. Bilim V, Yuuki K, Itoi T, Muto A, Kato T, Nagaoka A, et al. Double inhibition of XIAP and Bcl-2 axis is beneficial for retrieving sensitivity of renal cell cancer to apoptosis. Br J Cancer 2008; 98:941-949.
14. Dizdar L, Jünemann LM, Werner TA, Verde PE, Baldus SE, Stoecklein NH, et al. Clinicopathological and functional implications of the inhibitor of apoptosis proteins survivin and XIAP in esophageal cancer. Oncol Lett 2018; 15:3779-3789.
15. Yan Y, Mahotka C, Heikaus S, Shibata T, Wethkamp N, Liebmann J, et al. Disturbed balance of expression between XIAP and Smac/DIABLO during tumour progression in renal cell carcinomas. Br J Cancer 2004; 91:1349-1357.
16. Yan Y, Mahotka C, Heikaus S, Shibata T, Wethkamp N, Liebmann J, et al. Disturbed balance of expression between XIAP and Smac/DIABLO during tumour progression in renal cell carcinomas. Br J Cancer 2004; 91:1349-1357.
17. Obexer P, Ausserlechner MJ. X-linked inhibitor of apoptosis protein - a critical death resistance regulator and therapeutic target for personalized cancer therapy. Front Oncol 2014; 4:197.
18. Abbas R, Larisch S. Targeting XIAP for promoting cancer cell death—the story of ARTS and SMAC.  2020; 9:663-667.
19. Shi Y. A structural view of mitochondria-mediated apoptosis. Nat Struct Biol 2001; 8:394-401.
20. Fulda S, Vucic D. Targeting IAP proteins for therapeutic intervention in cancer. Nat Rev Drug Discov 2012; 11:109-124.
21. Meng Y, Tang W, Dai Y, Wu X, Liu M, Ji Q, et al. Natural BH3 mimetic (-)-gossypol chemosensitizes human prostate cancer via Bcl-xL inhibition accompanied by increase of Puma and Noxa. Mol Cancer Ther 2008; 7:2192-2202.
22. Prasanna R, Harish CC. Anticancer effect of a novel 2-arylidene-4,7-dimethyl indan-1-one against human breast adenocarcinoma cell line by G2/M cell cycle arrest. Oncol Res 2010; 18:461-468.
23. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25:402-408.
24. Mukund V, Behera SK, Alam A, Nagaraju GP. Molecular docking analysis of nuclear factor-κB and genistein interaction in the context of breast cancer. Bioinformation 2019; 15:11-17.
25. Suhail M PA, Husain A, Rehan M. Exploring inhibitory mechanisms of green tea catechins as inhibitors of a cancer therapeutic target, nuclear factor-κB (NF-κB). Biosci Biotech Res Asia 2019; 14.
26. Mastrangelo E, Cossu F, Milani M, Sorrentino G, Lecis D, Delia D, et al. Targeting the X-linked inhibitor of apoptosis protein through 4-substituted azabicyclo[5.3.0]alkane smac mimetics. Structure, activity, and recognition principles. J Mol Biol 2008; 384:673-689.
27. Nejabat M, Soltani F, Alibolandi M, Nejabat M, Abnous K, Hadizadeh F, et al. Smac peptide and doxorubicin-encapsulated nanoparticles: design, preparation, computational molecular approach and in vitro studies on cancer cells. J Biomol Struct Dyn 2020;1-13.
28. Giridharan S, Srinivasan M. Mechanisms of NF-κB p65 and strategies for therapeutic manipulation. J Inflamm Res 2018; 11:407-419.
29. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ 2018; 25:486-541.
30. Salvesen GS, Duckett CS. IAP proteins: blocking the road to death’s door. Nat Rev Mol Cell Biol 2002; 3:401-410.
31. Silke J, Hawkins CJ, Ekert PG, Chew J, Day CL, Pakusch M, et al. The anti-apoptotic activity of XIAP is retained upon mutation of both the caspase-3 and caspase-9 interacting sites. J Cell Biol 2002; 157:115-124.
32. Flygare JA, Beresini M, Budha N, Chan H, Chan IT, Cheeti S, et al. Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical candidate for the treatment of cancer (GDC-0152). J Med Chem 2012; 55:4101-4113.
33. Pucci B, Kasten M, Giordano A. Cell cycle and apoptosis. Neoplasia 2000; 2:291-299.
34. Shekhar TM, Burvenich IJG, Harris MA, Rigopoulos A, Zanker D, Spurling A, et al. Smac mimetics LCL161 and GDC-0152 inhibit osteosarcoma growth and metastasis in mice. BMC Cancer 2019; 19:924-952.
35. Martinez-Ruiz G, Maldonado V, Ceballos-Cancino G, Grajeda JP, Melendez-Zajgla J. Role of Smac/DIABLO in cancer progression. J Exp Clin Cancer Res 2008; 27:48-54.
36. Notarbartolo M, Cervello M, Poma P, Dusonchet L, Meli M, D’Alessandro N. Expression of the IAPs in multidrug resistant tumor cells. Oncol Rep 2004; 11:133-136.
37. Fong WG, Liston P, Rajcan-Separovic E, St. Jean M, Craig C, Korneluk RG. Expression and genetic analysis of XIAP-associated factor 1 (XAF1) in cancer cell lines. Genomics 2000; 70:113-122.
38. Tong QS, Zheng LD, Wang L, Zeng FQ, Chen FM, Dong JH, et al. Downregulation of XIAP expression induces apoptosis and enhances chemotherapeutic sensitivity in human gastric cancer cells. Cancer Gene Ther 2005; 12:509-514.
39. Hu W, Wang F, Tang J, Liu X, Yuan Z, Nie C, et al. Proapoptotic protein Smac mediates apoptosis in cisplatin-resistant ovarian cancer cells when treated with the anti-tumor agent AT101. J Biol Chem 2012; 287:68-80.
40. Berezovskaya O, Schimmer AD, Glinskii AB, Pinilla C, Hoffman RM, Reed JC, et al. Increased expression of apoptosis inhibitor protein XIAP contributes to anoikis resistance of circulating human prostate cancer metastasis precursor cells. Cancer Res 2005; 65:2378-2386.
41. Lu H, Wang J, Wang Y, Qiao L, Zhou Y. Embelin and its role in chronic diseases. Adv Exp Med Biol 2016; 928:397-418.
42. Fulda S. Promises and challenges of smac mimetics as cancer therapeutics. clin cancer res 2015; 21:5030-5036.
43. Prabhu KS, Achkar IW, Kuttikrishnan S, Akhtar S, Khan AQ, Siveen KS, et al. Embelin: A benzoquinone possesses therapeutic potential for the treatment of human cancer. Future Med Chem 2018; 10:961-976.
44. LaCasse EC, Mahoney DJ, Cheung HH, Plenchette S, Baird S, Korneluk RG. IAP-targeted therapies for cancer. Oncogene 2008; 27:6252-6275.
45. Mehrotra S, Languino LR, Raskett CM, Mercurio AM, Dohi T, Altieri DC. IAP regulation of metastasis. Cancer Cell 2010; 17:53-64.
46. Srinivasula SM, Ashwell JD. IAPs: what’s in a name? Mol Cell 2008; 30:123-135.

آمار
تعداد مشاهده مقاله: 1,075
تعداد دریافت فایل اصل مقاله: 477