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Amcasertib Increases Apoptosis While Decreasing Invasive and Migrating Abilities in Breast Cancer Stem Cells

Yıl 2024, Cilt: 14 Sayı: 3, 800 - 806, 30.09.2024
https://doi.org/10.33808/clinexphealthsci.1422121

Öz

Objective: A relationship exists between breast cancer stem cells (BCSCs) and the chemo-resistance and recurrence of aggressive breast tumors. Amcasertib is a small chemical compound and multiple kinase inhibitor that inhibits downstream Nanog and other cancer stem signaling pathways in cancer stem cells by targeting several serine-threonine kinases. In this study, we aimed to investigate the cytotoxicity
and anticancer effects of Amcasertib on BCSCs, gaining insight into the targetability of BCSCs.
Method: We used the combined xCELLigence-Real-Time Cell Analyzer (RTCA) equipment to analyze cytotoxicity and cell proliferation. We detected the IC50 dosages of Amcasertib at 24, 48, and 72 hours and examined its effects on apoptosis, cell cycle, invasion, and migration over 48 hours. We used flow cytometry for assays of apoptosis and cell cycle, and the CytoSelect 96-well Cell Migration and Invasion Assay
Kit for evaluating invasion and migration.
Results: Our results showed that Amcasertib has cytotoxic properties, with an IC50 dosage of 1.9 μM at the 48th hour. In addition, Amcasertib significantly induced apoptosis in BCSCs, despite not affecting the cell cycle. Moreover, Amcasertib decreased BCSCs’ invasion and migratory properties, part of epithelial-mesenchymal transition (EMT).
Conclusion: In conclusion, our findings provide crucial information for understanding the potential of Amcasertib in targeting BCSCs. In addition, we suggest that Amcasertib could be a beneficial drug for breast cancer treatment by targeting BCSCs.

Kaynakça

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Yıl 2024, Cilt: 14 Sayı: 3, 800 - 806, 30.09.2024
https://doi.org/10.33808/clinexphealthsci.1422121

Öz

Kaynakça

  • Wilkinson L, Gathani T. Understanding breast cancer as a global health concern. Br J Radiol. 2022;95(1130):20211033. DOI:10.1259/bjr.20211033.
  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249. DOI:10.3322/caac.21660.
  • Scully OJ, Bay BH, Yip G, Yu Y. Breast cancer metastasis. Cancer Genomics Proteomics. 2012;9(5):311-320.
  • Jin X, Mu P. Targeting Breast Cancer Metastasis. Breast Cancer (Auckl). 2015; 9(Suppl 1): 23-34. DOI:10.4137/BCBCR.S25460.
  • Jara L, Morales S, de Mayo T, Gonzalez-Hormazabal P, Carrasco V, Godoy R. Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations. Biol Res. 2017;50(1):35. DOI:10.1186/s40659-017-0139-2.
  • Amir E, Freedman OC, Seruga B, Evans DG. Assessing women at high risk of breast cancer: A review of risk assessment models. J Natl Cancer Inst. 2010;102(10):680-691. DOI:10.1093/jnci/djq088.
  • Turnbull C, Rahman N. Genetic predisposition to breast cancer: Past, present, and future. Annu Rev Genomics Hum Genet. 2008;9:321-345. DOI:10.1146/annurev.genom.9.081307.164339.
  • Weigelt B, Reis-Filho JS. Histological and molecular types of breast cancer: is there a unifying taxonomy? Nat Rev Clin Oncol. 2009;6(12):718-730. DOI:10.1038/nrclinonc.2009.166.
  • Boyle P. Triple-negative breast cancer: epidemiological considerations and recommendations. Ann Oncol. 2012;23(6S):vi7-12. DOI:10.1093/annonc/mds187.
  • Schnitt SJ. Classification and prognosis of invasive breast cancer: from morphology to molecular taxonomy. Mod Pathol. 2010;23(2S):S60-S64. DOI:10.1038/modpathol.2010.33.
  • Huang T, Song X, Xu D, Tiek D, Goenka A, Wu B, Sastry N, Hu B, Cheng SY. Stem cell programs in cancer initiation, progression, and therapy resistance. Theranostics. 2020;10(19):8721-8743. DOI:10.7150/thno.41648.
  • Yang L, Shi P, Zhao G, Xu J, Peng W, Zhang J, Zhang G, Wang X, Dong Z, Chen F, Cui H. Targeting cancer stem cell pathways for cancer therapy. Signal Transduct Target Ther. 2020;5(1):8. DOI:10.1038/s41392-020-0110-5.
  • Zhong L, Li Y, Xiong L, Wang W, Wu M, Yuan T, Yang W, Tian C, Miao Z, Wang T, Yang S. Small molecules in targeted cancer therapy: Advances, challenges, and future perspectives. Signal Transduct Target Ther. 2021;6(1):201. DOI:10.1038/s41392-021-00572-w.
  • Wu Q, Qian W, Sun X, Jiang S. Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021. J Hematol Oncol. 2022;15(1):143. DOI:10.1186/s13045-022-01362-9.
  • Landeros N, Castillo I, Pérez-Castro R. Preclinical and clinical trials of new treatment strategies targeting cancer stem cells in subtypes of breast cancer. Cells. 2023;12(5):720. DOI:10.3390/cells12050720.
  • Saha T, Lukong KE. Breast cancer stem-like cells in drug resistance: A review of mechanisms and novel therapeutic strategies to overcome drug resistance. Front Oncol. 2022;12:856974. DOI:10.3389/fonc.2022.856974.
  • Vasefifar P, Motafakkerazad R, Maleki LA, Najafi S, Ghrobaninezhad F, Najafzadeh B, Alemohammad H, Amini M, Baghbanzadeh A, Baradaran B. Nanog, as a key cancer stem cell marker in tumor progression. Gene. 2022;827:146448. DOI:10.1016/j.gene.2022.146448.
  • Jeter CR, Yang T, Wang J, Chao HP, Tang DG. Concise Review: NANOG in cancer stem cells and tumor development: an update and outstanding questions. Stem Cells. 2015;33(8):2381-2390. DOI:10.1002/stem.2007.
  • Grubelnik G, Boštjančič E, Pavlič A, Kos M, Zidar N. NANOG expression in human development and cancerogenesis. Exp Biol Med (Maywood). 2020;245(5):456-464. DOI:10.1177/1535370220905560.
  • Sonbol MB, Ahn DH, Bekaii-Saab T. Therapeutic targeting strategies of cancer stem cells in gastrointestinal malignancies. Biomedicines. 2019;7(1):17. DOI:10.3390/biomedicines7010017.
  • Lee RH, Wai KC, Chan JW, Ha PK, Kang H. Approaches to the management of metastatic adenoid cystic carcinoma. Cancers (Basel). 2022;14(22):5698. DOI:10.3390/cancers14225698.
  • Jia Z, Zhang Y, Yan A, Wang M, Han Q, Wang K, Wang J, Qiao C, Pan Z, Chen C, Hu D, Ding X. 1,25-dihydroxyvitamin D3 signaling-induced decreases in IRX4 inhibits NANOG-mediated cancer stem-like properties and gefitinib resistance in NSCLC cells. Cell Death Dis. 2020;11(8):670. DOI:10.1038/s41419-020-02908-w.
  • Guler Kara H, Ozates NP, Asik A, Gunduz C. Cancer stemness kinase inhibitor amcasertib: a promising therapeutic agent in ovarian cancer stem and cancer cell models with different genetic profiles. Med Oncol. 2023;40(12):342. DOI:10.1007/s12032-023-02210-7.
  • Data Sheet-Human Breast Cancer Stem Cell Culture (Triple Negative) [Internet]. Accessed [2024 Apr 19]. https://celprogen.com/content/uploads/product/1/15444904062.pdf
  • Ozdemir Kutbay N, Biray Avci C, Sarer Yurekli B, Caliskan Kurt C, Shademan B, Gunduz C, Erdogan M. Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells. J Biochem Mol Toxicol. 2020;34(10):e22547. DOI:10.1002/jbt.22547.
  • Butti R, Gunasekaran VP, Kumar TVS, Banerjee P, Kundu GC. Breast cancer stem cells: Biology and therapeutic implications. Int J Biochem Cell Biol. 2019;107(October 2018):38-52. DOI:10.1016/j.biocel.2018.12.001.
  • Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003;100(7):3983-3988. DOI:10.1073/pnas.0530291100.
  • Palomeras S, Ruiz-Martínez S, Puig T. Targeting breast cancer stem cells to overcome treatment resistance. Molecules. 2018;23(9):2193. DOI:10.3390/molecules23092193.
  • Zheng Q, Zhang M, Zhou F, Zhang L, Meng X. The breast cancer stem cells traits and drug resistance. Front Pharmacol. 2021;11:599965. DOI:10.3389/fphar.2020.599965.
  • Hallett RM, Kondratyev MK, Giacomelli AO, Nixon AML, Girgis-Gabardo A, Ilieva D, Hassell JA. Small molecule antagonists of the Wnt/β-catenin signaling pathway target breast tumor-initiating cells in a Her2/Neu mouse model of breast cancer. PLoS One. 2012;7(3):e33976. DOI:10.1371/journal.pone.0033976.
  • Zheng FM, Long ZJ, Hou ZJ, Luo Y, Xu LZ, Xia JL, Lai XJ, Liu JW, Wang X, Kamran M, Yan M, Shao SJ, Lam EWF, Wang SW, Lu G, Liu Q. A novel small molecule Aurora kinase inhibitor attenuates breast tumor-initiating cells and overcomes drug resistance. Mol Cancer Ther. 2014;13(8):1991-2003. DOI:10.1158/1535-7163.MCT-13-1029.
  • Jang GB, Hong IS, Kim RJ, Lee SY, Park SJ, Lee ES, Park JH, Yun CH, Chung JU, Lee KJ, Lee HY, Nam JS. Wnt/β-catenin small-molecule inhibitor CWP232228 preferentially inhibits the growth of breast cancer stem-like cells. Cancer Res. 2015;75(8):1691-1702. DOI:10.1158/0008-5472.CAN-14-2041.
  • Viswanadhapalli S, Luo Y, Sareddy GR, Santhamma B, Zhou M, Li M, Ma S, Sonavane R, Pratap UP, Altwegg KA, Li X, Chang A, Chavez-Riveros A, Dileep K V., Zhang KYJ, Pan X, Murali R, Bajda M, Raj G V., Brenner AJ, Manthati V, Rao MK, Tekmal RR, Nair HB, Nickisch KJ, Vadlamudi RK. EC359: A first-in-class small-molecule inhibitor for targeting oncogenic LIFR signaling in triple-negative breast cancer. Mol Cancer Ther. 2019;18(8):1341-1354. DOI:10.1158/1535-7163.MCT-18-1258.
  • Liu C, Zhang Y, Gao J, Zhang Q, Sun L, Ma Q, Qiao X, Li X, Liu J, Bu J, Zhang Z, Han L, Zhao D, Yang Y. A highly potent small-molecule antagonist of exportin-1 selectively eliminates CD44+CD24- enriched breast cancer stem-like cells. Drug Resist Updat. 2023;66:100903. DOI:10.1016/j.drup.2022.100903.
  • Sato K, Padgaonkar AA, Baker SJ, Cosenza SC, Rechkoblit O, Subbaiah DRCV, Domingo-Domenech J, Bartkowski A, Port ER, Aggarwal AK, Ramana Reddy M V, Irie HY, Reddy EP. Simultaneous CK2/TNIK/DYRK1 inhibition by 108600 suppresses triple negative breast cancer stem cells and chemotherapy-resistant disease. Nat Commun. 2021;12(1):4671. DOI:10.1038/s41467-021-24878-z.
  • Seo J, Park M, Ko D, Kim S, Park JM, Park S, Nam KD, Farrand L, Yang J, Seok C, Jung E, Kim YJ, Kim JY, Seo JH. Ebastine impairs metastatic spread in triple-negative breast cancer by targeting focal adhesion kinase. Cell Mol Life Sci. 2023;80(5):132. DOI:10.1007/s00018-023-04760-5.
  • Wang Y, Lv Z, Chen F, Wang X, Gou S. Conjugates derived from lapatinib derivatives with cancer cell stemness inhibitors effectively reversed drug resistance in triple-negative breast cancer. J Med Chem. 2021;64(17):12877-12892. DOI:10.1021/acs.jmedchem.1c01013.
  • Bethesda (MD):National Library of Medicine; 2000 Feb 29-. Identifier NCT02432326.A study of BBI608 and BBI503 administered in combination to adult patients with advanced solid tumors; 2015 May 4. Accessed [2023 Feb 9]. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02432326?term=NCT02432326&draw=2&rank=1
  • Bethesda (MD):National Library of Medicine; 2000 Feb 29-. Identifier NCT02354898.A study of BBI503 in advanced solid tumors, or BBI503/ Sorafenib in advanced hepatocellular carcinoma; 2015 Feb 3. Accessed [2023 Feb 9]. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02354898?term=NCT02354898&draw=2&rank=1
  • Bethesda (MD):National Library of Medicine; 2000 Feb 29-. Identifier NCT02279719. A study of BBI608 in combination with sorafenib, or BBI503 in combination with sorafenib in adult patients with hepatocellular carcinoma; 2021 Sep 9. Accessed [2023 Feb 9]. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02279719?cond=NCT02279719&draw=2&rank=1
  • Bethesda (MD):National Library of Medicine; 2000 Feb 29-. Identifier NCT02483247.A study of BBI503 in combination with selected anti-cancer therapeutics in adult patients with advanced cancer; 2015 Jun 26. Accessed [2023 Feb 9]. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02483247?term=NCT02483247&draw=2&rank=1
  • Bethesda (MD):National Library of Medicine; 2000 Feb 29-. Identifier NCT02232633. A study of BBI503 in adult patients with advanced hepatobiliary Cancer; 2014 Sep 5. Accessed [2023 Feb 9]. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02232633?cond=NCT02232633&draw=2&rank=1
  • Bethesda (MD):National Library of Medicine; 2000 Feb 29-. Identifier NCT01781455. A study of BBI503 in adult patients with advanced solid tumors; 2013 Feb 1. Accessed [2023 Feb 9]. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01781455?term=NCT01781455&draw=2&rank=1
  • Yu RMC, Selvarajah GT, Tan GC, Cheah YK. In vitro growth inhibition, caspase-dependent apoptosis, and S and G2/M phase arrest in breast cancer cells induced by fluorine-incorporated gold I compound, Ph3PAu[SC(OMe)=NC6H4F-3]. Int J Breast Cancer. 2022;2022(1):7168210. DOI:10.1155/2022/7168210.
  • Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. Journal of Clinical Investigation. 2009;119(6):1420–8. DOI:10.1172/JCI39104.
  • Chang JC. Cancer stem cells: Role in tumor growth, recurrence, metastasis, and treatment resistance. Medicine. 2016;95(1S):S20-S25. DOI:10.1097/MD.0000000000004766.
  • Wang D, Lu P, Zhang H, Luo M, Zhang X, Wei X, Gao J, Zhao Z, Liu C. Correction: Oct-4 and Nanog promote the epithelial-mesenchymal transition of breast cancer stem cells and are associated with poor prognosis in breast cancer patients. Oncotarget. 2021;12(10):1024-1025. DOI:10.18632/oncotarget.27791.
  • Li J, Gao R, Zhang J. USP22 contributes to chemoresistance, stemness, and EMT phenotype of triple-negative breast cancer cells by egulating the warburg effect via c-Myc deubiquitination. Clin Breast Cancer. 2023;23(2):162-175. DOI:10.1016/j.clbc.2022.11.006.
  • Organization WH. WHO Drug Information 2015, vol. 29, 2 [full issue]. WHO Drug Information. 2015;29(2):125-194.
Toplam 49 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Kanser Hücre Biyolojisi, Moleküler Hedefler
Bölüm Articles
Yazarlar

Aycan Aşık 0000-0002-4123-4175

Hale Guler Kara 0000-0002-4304-3727

Neslihan Pınar Özateş 0000-0001-6856-4644

Cumhur Gündüz 0000-0002-6593-3237

Erken Görünüm Tarihi 27 Eylül 2024
Yayımlanma Tarihi 30 Eylül 2024
Gönderilme Tarihi 22 Ocak 2024
Kabul Tarihi 4 Temmuz 2024
Yayımlandığı Sayı Yıl 2024 Cilt: 14 Sayı: 3

Kaynak Göster

APA Aşık, A., Guler Kara, H., Özateş, N. P., Gündüz, C. (2024). Amcasertib Increases Apoptosis While Decreasing Invasive and Migrating Abilities in Breast Cancer Stem Cells. Clinical and Experimental Health Sciences, 14(3), 800-806. https://doi.org/10.33808/clinexphealthsci.1422121
AMA Aşık A, Guler Kara H, Özateş NP, Gündüz C. Amcasertib Increases Apoptosis While Decreasing Invasive and Migrating Abilities in Breast Cancer Stem Cells. Clinical and Experimental Health Sciences. Eylül 2024;14(3):800-806. doi:10.33808/clinexphealthsci.1422121
Chicago Aşık, Aycan, Hale Guler Kara, Neslihan Pınar Özateş, ve Cumhur Gündüz. “Amcasertib Increases Apoptosis While Decreasing Invasive and Migrating Abilities in Breast Cancer Stem Cells”. Clinical and Experimental Health Sciences 14, sy. 3 (Eylül 2024): 800-806. https://doi.org/10.33808/clinexphealthsci.1422121.
EndNote Aşık A, Guler Kara H, Özateş NP, Gündüz C (01 Eylül 2024) Amcasertib Increases Apoptosis While Decreasing Invasive and Migrating Abilities in Breast Cancer Stem Cells. Clinical and Experimental Health Sciences 14 3 800–806.
IEEE A. Aşık, H. Guler Kara, N. P. Özateş, ve C. Gündüz, “Amcasertib Increases Apoptosis While Decreasing Invasive and Migrating Abilities in Breast Cancer Stem Cells”, Clinical and Experimental Health Sciences, c. 14, sy. 3, ss. 800–806, 2024, doi: 10.33808/clinexphealthsci.1422121.
ISNAD Aşık, Aycan vd. “Amcasertib Increases Apoptosis While Decreasing Invasive and Migrating Abilities in Breast Cancer Stem Cells”. Clinical and Experimental Health Sciences 14/3 (Eylül 2024), 800-806. https://doi.org/10.33808/clinexphealthsci.1422121.
JAMA Aşık A, Guler Kara H, Özateş NP, Gündüz C. Amcasertib Increases Apoptosis While Decreasing Invasive and Migrating Abilities in Breast Cancer Stem Cells. Clinical and Experimental Health Sciences. 2024;14:800–806.
MLA Aşık, Aycan vd. “Amcasertib Increases Apoptosis While Decreasing Invasive and Migrating Abilities in Breast Cancer Stem Cells”. Clinical and Experimental Health Sciences, c. 14, sy. 3, 2024, ss. 800-6, doi:10.33808/clinexphealthsci.1422121.
Vancouver Aşık A, Guler Kara H, Özateş NP, Gündüz C. Amcasertib Increases Apoptosis While Decreasing Invasive and Migrating Abilities in Breast Cancer Stem Cells. Clinical and Experimental Health Sciences. 2024;14(3):800-6.

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