Casticin: A Promising Candidate to Develop a Stem Cell Targeted Strategy in AML Treatment

Year 2020, Volume: 4 Issue: 3, 297 - 304, 01.09.2020

Tugba Erkmen Belgin Sert Serdar Halil Ates Pembe Keskinoglu Semra Kocturk

https://doi.org/10.30621/jbachs.2020.1226

Abstract

Purpose: Acute myeloid leukemia is the most common form of acute leukemia with genetic and epigenetic heterogeneity. Although current therapeutic agents provide successful remission, 5-year survival rates are still low. Insufficiency of targeting leukemia stem cells is considered as the main obstacle that causes drug resistance and relapse. Phytochemicals remain a promising source for targeted drug research. Studies showed that Casticin has antiproliferative effects on leukemic cells, but its effects on leukemic stem cells are still unclear. In this study, we aimed to investigate the antiproliferative capacity of Casticin on acute myeloid leukemia stem-like KG1a cells and its relatively mature parental KG1 cells in comparison with healthy peripheral blood mononuclear cells PBMC . Method: The antiproliferative effects of Casticin on cells and IC50 values were determined by MTT test. The effects of Casticin on caspase 3/7 activity, apoptosis and necrosis in cells were evaluated by flow cytometry and TUNEL assays. Results: 2 μM Casticin treatment for 24 h was increased apoptotic cell death and caspase 3/7 activation in KG1 27.2%; 17.30%; p

Keywords

apoptosis, acute myeloid leukemia, Casticin, cancer stem cells

References

• 1. Löwenberg B, Rowe JM. Introduction to the review series on advances in acute myeloid leukemia (AML). Blood 2016;127:1. [CrossRef]
• 2. Carraway HE. Improving overall survival in older adults with acute myeloid leukemia: subpopulations matter. Am Soc Clin Oncol 2018;36:3186–3188. [CrossRef]
• 3. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997;3:730–737. [CrossRef]
• 4. Darwish NHE, Mousa SA. Intrinsic targeting strategies against acute myeloid leukemic stem cells. Integr Cancer Sci Therap 2015. [CrossRef]
• 5. Thomas D, Majeti R. Biology and relevance of human acute myeloid leukemia stem cells. Blood 2017;129:1577–1585. [CrossRef]
• 6. Hu L, Cao D, Li Y, He Y, Guo K. Resveratrol sensitized leukemia stem cell-like KG-1a cells to cytokine-induced killer cells-mediated cytolysis through NKG2D ligands and TRAIL receptors. Cancer Biol Ther 2012;13:516–526. [CrossRef]
• 7. Mahbub AA, Le Maitre CL, Haywood-Small SL, McDougall GJ, Cross NA, Jordan-Mahy N. Differential effects of polyphenols on proliferation and apoptosis in human myeloid and lymphoid leukemia cell lines. Anti-cancer Agents Med Chem 2013;13:1601– 1613. [CrossRef]
• 8. Zeng Y, Weng G, Fan J, et al. Curcumin reduces the expression of survivin, leading to enhancement of arsenic trioxide-induced apoptosis in myelodysplastic syndrome and leukemia stem-like cells. Oncology Rep 2016;36:1233–1242. [CrossRef]
• 9. Degterev A, Boyce M, Yuan J. A decade of caspases. Oncogene 2003;22:8543–8567. [CrossRef]
• 10. Radogna F, Dicato M, Diederich M. Cancer-type-specific crosstalk between autophagy, necroptosis and apoptosis as a pharmacological target. Biochem Pharmacol 2015;94:1–11. [CrossRef]
• 11. Hanahan D. Rethinking the war on cancer. Lancet 2014;383:558–563. [CrossRef]
• 12. Testa U, Riccioni R. Deregulation of apoptosis in acute myeloid leukemia. Haematologica 2007;92:81–94. [CrossRef]
• 13. Su Z, Yang Z, Xie L, DeWitt JP, Chen Y. Cancer therapy in the necroptosis era. Cell Death Differ 2016;23:748–756. [CrossRef]
• 14. Seifert L, Werba G, Tiwari S, et al. The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression. Nature 2016;532:245–249. [CrossRef]
• 15. Jin J, Shen J-K, Du H-p, Yang M, Wang Y-G. Apoptosis Was Induced by Casticin in Acute Myelocytic Leukemia Cells. Blood 2008;112:3991. [CrossRef]
• 16. Shen J-K, Du H-P, Yang M, Wang Y-G, Jin J. Casticin induces leukemic cell death through apoptosis and mitotic catastrophe. Ann Hematol 2009;88:743–752. [CrossRef]
• 17. Kikuchi H, Yuan B, Yuhara E, Takagi N, Toyoda H. Involvement of histone H3 phosphorylation through p38 MAPK pathway activation in casticin-induced cytocidal effects against the human promyelocytic cell line HL-60. Int J Oncol 2013;43:2046–2056. [CrossRef]
• 18. Righeschi C, Eichhorn T, Karioti A, Bilia AR, Efferth T. Microarraybased mRNA expression profiling of leukemia cells treated with the flavonoid, casticin. Cancer Genomics Proteomics 2012;9:143–151. http://cgp.iiarjournals.org/content/9/3/143.long
• 19. Dragu DL, Necula LG, Bleotu C, Diaconu CC, Chivu-Economescu M. Therapies targeting cancer stem cells: Current trends and future challenges. World J Stem Cells 2015;7:1185–1201. [CrossRef]
• 20. Siveen KS, Uddin S, Mohammad RM. Targeting acute myeloid leukemia stem cell signaling by natural products. Mol Cancer 2017;16:13. [CrossRef]
• 21. Lee G-Y, Jeong S-Y, Lee H-R, Oh I-H. Age-related differences in the bone marrow stem cell niche generate specialized microenvironments for the distinct regulation of normal hematopoietic and leukemia stem cells. Sci Rep 2019;9:1007. [CrossRef]
• 22. Fox JL, MacFarlane M. Targeting cell death signalling in cancer: minimising ‘Collateral damage’. Br J Cancer 2016;115:5–11. [CrossRef]
• 23. Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994;367:645–648. [CrossRef]
• 24. Jordan CT, Guzman ML, Noble M. Cancer stem cells. N Engl J Med 2006;355:1253–1261. [CrossRef]
• 25. Otsuka T, Ogo T, Eto T, Asano Y, Suganuma M, Niho Y. Growth inhibition of leukemic cells by (-)-epigallocatechin gallate, the main constituent of green tea. Life Sci 1998;63:1397–1403. [CrossRef]
• 26. Li YJ, Xu HJ. Relationship between apoptotic effect of Resveratrol on KG-1 cells and expression of bcl-2/bax. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2008;16:1026–1029. https://europepmc.org/article/ med/18928588
• 27. Dhanasekaran S, Biswal BK, Sumantran VN, Verma RS. Augmented sensitivity to methotrexate by curcumin induced overexpression of folate receptor in KG-1 cells. Biochimie 2013;95:1567–1573. [CrossRef]
• 28. Naimi A, Entezari A, Hagh MF, Hassanzadeh A, Saraei R, Solali S. Quercetin sensitizes human myeloid leukemia KG-1 cells against TRAIL-induced apoptosis. J Cell Physiol 2019;234:13233–13241. [CrossRef]
• 29. Samudio I, Konopleva M, Carter B, Andreeff M. Apoptosis in leukemias: regulation and therapeutic targeting. In: Nagarajan L, editor. Acute Myelogenous Leukemia. Cancer Treatment and Research, vol. 145. New York, NY: Springer; 2009. [CrossRef]
• 30. Brentnall M, Rodriguez-Menocal L, De Guevara RL, Cepero E, Boise LH. Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis. BMC Cell Biol 2013;14:32. [CrossRef]