Volume 10, Issue 2 (2019)                   JMBS 2019, 10(2): 193-200 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Asgari F, Mahinpour R, Haghighipour N, Moradi L. Investigation of toxicity effect of 4-MePgC and 4-No2pgC two derivatives dihydropyrano [2,3-g] chromene on the K562 cell line (chronic myeloid leukaemia). JMBS 2019; 10 (2) :193-200
URL: http://biot.modares.ac.ir/article-22-13514-en.html
1- Biotechnology Department, Chemistry Faculty, University of Kashan, Kashan, Iran
2- Biotechnology Department, Chemistry Faculty, University of Kashan, Kashan, Iran, Mahinpour R.: Organic Chemistry Laboratory, Chemistry Faculty, University of Kashan, Qotb-e Ravandi Boulevard, Kashan, Iran. Postal Code: 8731753153 Haghighipour N.: National Cell Bank of Iran, Pasteur Institute of Iran, No. 69, Pasteur Street, Tehran , mahinpur@kashanu.ac.ir
3- National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran
4- Organic Chemistry Department, Chemistry Faculty, University of Kashan, Kashan, Iran
Abstract:   (6520 Views)
Chronic myeloid leukemia (CML) is a malignant blood disease with a particular chromosomal aberration and it is known as a common form of leukemia. Chromene family exhibit strong anti-cancer effects. Therefore, in this study, the effect of two derivatives of dihydro-pyrano [2, 3-g] chromene family is investigated on cell toxicity and apoptosis induction in K562 cancer cells and compared them with Peripheral Blood Mononuclear (PBMC) normal cells. The K562 cell line was cultured in the presence of the mentioned chromene derivatives at a concentration of 40-200µM for 24-72 hours. The effect of these compounds on growth and viability of K562 cell line and PBMC cells were studied via MTT assay and apoptosis induction was investigated by flow cytometry. The results showed that these chromene derivatives inhibit K562 cell line growth. Moreover, increasing the chromene concentration and the time of exposure to it increase the cell toxicity. Among these compounds, 4-No2pgC was known as a compound with high toxicity (IC50=129±2.75) and 4-MePgC recognized as a compound with low toxicity (IC50=214±3.42) after 72 hours exposure to the K562 cell line. Furthermore, the results of flow cytometry demonstrated the effect of apoptosis induction of these compounds on the K562 cell line. According to the obtained results from this research, chromene derivatives can induce apoptosis in the K562 cell line and these compounds have a less toxic effect on normal cells than cancer cells. In conclusion, these derivatives can be considered as a proper candidate for the treatment of leukemia.
Full-Text [PDF 1297 kb]   (1577 Downloads)    
Article Type: Research Paper | Subject: Agricultural Biotechnology
Received: 2017/10/18 | Accepted: 2018/03/6 | Published: 2019/06/20

1. Deininger MWN, Goldman JM, Melo JV. The molecular biology of chronic myeloid leukemia. Blood. 2000;96(10):3343-52. [Link]
2. Costa M, Dias TA, Brito A, Proença F. Biological importance of structurally diversified chromenes. Eur J Med Chem. 2016;123:487-507. [Link] [DOI:10.1016/j.ejmech.2016.07.057]
3. Roşca A, Arion C, Coliłă A, Nedelcu L, Scîrneciu C, Andreescu O, et al. Chronic myelogenous leukemia prognosis and evolution. Bull Transilv Univ Braşov. 2009;2(51):97-104. [Link]
4. Pane F, Intrieri M, Quintarelli C, Izzo B, Muccioli GC, Salvatore F. BCR/ABL genes and leukemic phenotype: From molecular mechanisms to clinical correlations. Oncogene. 2002;21(56):8652-67. [Link] [DOI:10.1038/sj.onc.1206094]
5. Kemnitzer W, Drewe J, Jiang S, Zhang H, Zhao J, Crogan-Grundy C, et al. Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 3. structure-activity relationships of fused rings at the 7,8-positions. J Med Chem. 2007;50(12):2858-64. [Link] [DOI:10.1021/jm070216c]
6. Wong S, Mc Laughlin J, Cheng D, Witte ON. Cell context-specific effects of the BCR-ABL oncogene monitored in hematopoietic progenitors. Blood. 2003;101(10):4088-97. [Link] [DOI:10.1182/blood-2002-11-3376]
7. Yu Y, Guo H, Li X. An improved procedure for the three‐component synthesis of benzo[g]chromene derivatives using basic ionic liquid. J Heterocycl Chem. 2011;48(6):1264-8. [Link] [DOI:10.1002/jhet.747]
8. Mahdavi M, Davoodi J, Zali MR, Foroumadi AR. Concomitant activation of caspase-9 and down-regulation of IAP proteins as a mechanism of apoptotic death in HepG2, T47D and HCT-116 cells upon exposure to a derivative from 4-aryl-4H-chromenes family. Biomed Pharmacother. 2011;65(3):175-82. [Link] [DOI:10.1016/j.biopha.2011.03.001]
9. Gourdeau H, Leblond L, Hamelin B, Desputeau C, Dong K, Kianicka I, et al. Antivascular and antitumor evaluation of 2-amino-4-(3-bromo-4,5-dimethoxy-phenyl)-3-cyano-4H-chromenes, a novel series of anticancer agents. Mol Cancer Ther. 2004;3(11):1375-84. [Link]
10. Moradi L, Aghamohammad Sadegh M. Sodium saccharin as an effective catalyst for rapid one-pot pseudo-five component synthesis of dihydropyra-no[[2,3-g]]chromenes under microwave irradiation. Acta Chimica Slovenica. 2017;64:506-12. [Link] [DOI:10.17344/acsi.2017.3417]
11. Galluzzi L, Morselli E, Kepp O, Vitale I, Rigoni A, Vacchelli E, et al. Mitochondrial gateways to cancer. Mol Aspects Med. 2010;31(1):1-20. [Link] [DOI:10.1016/j.mam.2009.08.002]
12. Lu MC, Yang SH, Hwang SL, Lu YJ, Lin YH, Wang SR, et al. Induction of G2/M phase arrest by squamocin in chronic myeloid leukemia (K562) cells. Life Sci. 2006;78(20):2378-83. [Link] [DOI:10.1016/j.lfs.2005.09.048]
13. Kasibhatla S, Gourdeau H, Meerovitch K, Drewe J, Reddy S, Qiu L, et al. Discovery and mechanism of action of a novel series of apoptosis inducers with potential vascular targeting activity. Mol Cancer Ther. 2004;3(11):1365-74. [Link]
14. Aryapour H, Riazi GH, Ahmadian Sh, Foroumadi AR, Mahdavi M, Emami S. Induction of apoptosis through tubulin inhibition in human cancer cells by new chromene-based chalcones. Pharm Biol. 2012;50(12):1551-60. [Link] [DOI:10.3109/13880209.2012.695799]
15. Rahimi R, Mahdavi M, Pejman S, Zare P, Balalaei S. Inhibition of cell proliferation and induction of apoptosis in K562 human leukemia cells by the derivative (3-NpC) from dihydro-pyranochromenes family. Acta Biochimica Polonica. 2015;62(1):83-8. [Link] [DOI:10.18388/abp.2014_825]
16. Keerthy HK, Garg M, Mohan CD, Madan V, Kanojia D, Shobith R, et al. Synthesis and Characterization of Novel 2-Amino-Chromene-Nitriles that Target Bcl-2 in Acute Myeloid Leukemia Cell Lines. PLoS One. 2014;9(9):e107118. [Link] [DOI:10.1371/journal.pone.0107118]
17. Dosik GM, Barlogie B, Johnston D, Mellard D, Freireich EJ. Dose-dependent suppression of DNA synthesis in vitro as a predictor of clinical response in adult acute myeloblastic leukemia. Eur J Cancer. 1981;17(5):549-55. [Link] [DOI:10.1016/0014-2964(81)90057-8]
18. Van Haaften RI, Evelo CT, Haenen GR, Bast A. No reduction of alpha-tocopherol quinone by glutathione in rat liver microsomes. Biochem Pharmacol. 2001;61(6):715-9. [Link] [DOI:10.1016/S0006-2952(01)00545-7]

Add your comments about this article : Your username or Email:

Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.