Document Type : Research articles
Authors
- Parisa Heydari 1
- Mojgan Noroozi-Karimabad Noroozi-Karimabad 2
- Zahra Sheikh rezaee 1
- Ali Darekordi 3
- Maryam Fekri Soofi Aadi 1
- Ahmad Fatemi 1
- Gholamhossein Hasanshahi 4
1 Department of Hematology, Kerman University of Medical Science, Kerman, Iran
2 Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
3 Department of Chemistry, Faculty of Science, Vali-e-Asr University of Rafsanjan, Rafsanjan, Iran
4 Department of Hematology, Kerman University of Medical Science, Kerman, Iran Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
Abstract
Background: Heterocyclic compounds are generally introduced as important valuable sources of pharmacologically active compounds. Amongst these compounds, the indole is largely distributed within the bioactive molecules, containing antitumor agents. Due to their unique physiochemical and biological properties, indole and its derivatives have been used as privileged scaffolds for designing antitumor agents.
Objectives: The current experimental study aimed to evaluate the anti-cancer effects of a novel compound with indole-core-base on acute myeloid leukemia (AML) cells.
Methods: Following being cultured, AML cells that had been multiplicities were treated by the demonstrated concentration of novel indole compounds (at doses of 100-300µg/mL) for 24 h. The percentage of living and dead cells was subsequently determined by trypan bluedye (MERK, Germany). The survival rate of treated cells was also examined by MTT assay. The calculated fold changes of the studied genes expression against ?-actin were determined by the real-time polymerase chain reaction (PCR) technique. The collected data were statistically analyzed by student t-test and repeated measure test.
Results: Results showed that the intended novel indole-core-based derivative (C18H10N2F6O) followed both dose-dependent cytotoxic and anti-proliferative patterns on the AML cell line. The compound was able to induce apoptosis in 50% of the cells at the dose of 250µg/mL. Real-time PCR analysis indicated that in compound-treated cells the gene expression level of Bcl-2 has been downregulated, while Bax was upregulated, compared to untreated control cells.
Conclusion: Despite the lack of knowledge in this regard, in this study, results of this leading mechanism(s) that may run by the compound indicated that indole3carbaldehyde derivative has cytotoxic effects on AML cells in a dose-dependent fashion.
Keywords
- Montagna D, Maccario R, Montini E, Tonelli R, Lisini D, Pagani S, et al. Generation and ex vivo expansion of cytotoxic T lymphocytes directed toward different types of leukemia or myelodysplastic cells using both HLA-matched and partially matched donors. Exp Hematol. 2003;31(11):1031-8. doi: 10.1016/s0301-472x(03)00230-3. [PubMed: 14585366].
- Soodeh N, Fatemeh N, Ahmad K, Hossein D, Hossein R, Shahrbanoo R, et al. Effect of HESA-A on acute promyelocytic cell line (NB4). Payavard Salamat. 2012;6(3):67-76.
- Longo DL, Fauci AS, Kasper D, Hauser S, Jameson J, Loscalzo J. Harrison’s principles of internal medicine. New York: McGraw-Hill Companies; 2012. P. 3287.
- McPherson RA, Pincus MR. Henry's clinical diagnosis and management by laboratory methods. New York: Elsevier Health Sciences; 2016.
- Gottesman MM. Mechanisms of cancer drug resistance. Annu Rev Med. 2002;53(1):615-27. doi: 10.1146/annurev.med.53.082901.103929. [PubMed: 11818492].
- Darehkordi A, Rahmani F, Hashemi V. Synthesis of new trifluoromethylated indole derivatives. Tetrahedron Lett. 2013;54(35):4689-92. doi: 10.1016/j.tetlet.2013.06.093.
- Celik I, Tuluce Y. Effects of indoleacetic acid and kinetin on lipid peroxidation and antioxidant defense in various tissues of rats. Pestic Biochem Physiol. 2006;84(1):49-54. doi: 10.1016/j.pestbp.2005.05.004.
- Karimabad MN, Mahmoodi M, Jafarzadeh A, Darekordi A, Hajizadeh MR, Hassanshahi G. Molecular targets, anti-cancer properties and potency of synthetic indole-3-carbinol derivatives. Mini Rev Med Chem. 2019;19(7):540-54. doi: 10.2174/1389557518666181116120145. [PubMed: 30444199].
- Steinmetz KA, Potter JD. Vegetables, fruit, and cancer prevention: a review. J Am Diet Assoc. 1996;96(10):1027-39. doi: 10.1016/S0002-8223(96)00273-8. [PubMed: 8841165].
- Weng JR, Tsai CH, Kulp SK, Chen CS. Indole-3-carbinol as a chemopreventive and anti-cancer agent. Cancer Lett. 2008;262(2):153-63. doi: 10.1016/j.canlet.2008.01.033. [PubMed: 18314259].
- Weng JR, Omar H, Kulp S, Chen CS. Pharmacological exploitation of indole-3-carbinol to develop potent antitumor agents. Mini Rev Med Chem. 2010;10(5):398-404. doi: 10.2174/138955710791330945. [PubMed: 20370707].
- Telang N, Katdare M. Epithelial cell culture models for the prevention and therapy of clinical breast cancer (Review). Oncol Lett. 2012;3(4):744-50. doi: 10.3892/ol.2012.561. [PubMed: 22740986].
- Ahmad A, Sakr WA, Rahman K. Mechanisms and therapeutic implications of cell death induction by indole compounds. Cancers. 2011;3(3):2955-74. doi: 10.3390/cancers3032955. [PubMed: 24212940].
- Jafarian AH, Forooshani MK, Takallou L, Roshan NM. CD10 expression in gastric carcinoma is correlated with tumor grade and survival. Univ Med. 2019;38(1):41-7. doi: 10.18051/UnivMed.2019.v38.41-47.
- Wang TT, Schoene NW, Milner JA, Kim YS. Broccoli‐derived phytochemicals indole‐3‐carbinol and 3, 3′‐diindolylmethane exerts concentration‐dependent pleiotropic effects on prostate cancer cells: Comparison with other cancer preventive phytochemicals. Mol Carcinog. 2012;51(3):244-56. doi: 10.1002/mc.20774. [PubMed: 21520295].
- Frydoonfar HR, McGrath DR, Spigelman AD. The effect of indole‐3‐carbinol and sulforaphane on a prostate cancer cell line. ANZ J Surg. 2003;73(3):154-6. doi: 10.1046/j.1445-2197.2003.02652.x. [PubMed: 12608980].
- Goldberg A, Titorenko V, Beach A, Abdelbaqi K, Safe S, Sanderson J. Ring-substituted analogs of 3, 3′-diindolylmethane (DIM) induce apoptosis and necrosis in androgen-dependent and–independent prostate cancer cells. Investig New Drugs. 2014;32(1):25-36. doi: 10.1007/s10637-013-9979-y. [PubMed: 23709189].
- Aggarwal BB, Ichikawa H. Molecular targets and anticancer potential of indole-3-carbinol and its derivatives. Cell Cycle. 2005;4(9):1201-15. doi: 10.4161/cc.4.9.1993. [PubMed: 16082211].
- Aggarwal BB, Shishodia S. Molecular targets of dietary agents for prevention and therapy of cancer. Biochem Pharmacol. 2006;71(10):1397-421. doi: 10.1016/j.bcp.2006.02.009. [PubMed: 16563357].
- Kim YS, Milner J. Targets for indole-3-carbinol in cancer prevention. J Nutr Biochem. 2005;16(2):65-73. doi: 10.1016/j.jnutbio.2004.10.007. [PubMed: 15681163].
- Kim YS, Milner JA. Bioactive food components and cancer-specific metabonomic profiles. Biomed Res Int. 2010;2011:721213. doi: 10.1155/2011/721213. [PubMed: 21113295].
- Rogan EG. The natural chemopreventive compound indole-3-carbinol: state of the science. In Vivo. 2006;20(2):221-8. [PubMed: 16634522].
- Karimabad MN, Mahmoodi M, Jafarzadeh A, Darehkordi A, Hajizadeh MR, Khorramdelazad H, et al. Evaluating of OCT-4 and NANOG was differentially regulated by a new derivative indole in leukemia cell line. Immunol Lett. 2017;190:7-14. doi: 10.1016/j.imlet.2017.06.012. [PubMed: 28690187].
- Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood. 2008;111(5):2505-15. doi: 10.1182/blood-2007-07-102798. [PubMed: 18299451].
- Biondi A, Testi AM, Gibson BE. Acute promyelocytic leukaemia. Mol Targeted Ther Childhood Cancer. 2010;9(5):83-108. doi: 10.1007/978-0-387-69062-9_5.
- Alimoghaddam K. A review of arsenic trioxide and acute promyelocytic leukemia. Int J Hematol Oncol Stem Cell Res. 2014;8(3):44-54. [PubMed: 25642308].
- Rego EM, de Santis GC. Differentiation syndrome in promyelocytic leukemia: clinical presentation, pathogenesis and treatment. Mediterr J Hematol Infect Dis. 2011;3(1):e2011048. doi: 10.4084/MJHID.2011.048. [PubMed: 22110898].
- Mo J, Xia Y, Ning Z, Wade TJ, Mumford JL. Elevated human telomerase reverse transcriptase gene expression in blood cells associated with chronic arsenic exposure in Inner Mongolia, China. Environ Health Perspect. 2009;117(3):354-60. doi: 10.1289/ehp.11532. [PubMed: 19337508].
- Kim DJ, Reddy K, Kim MO, Li Y, Nadas J, Cho YY, et al. (3-Chloroacetyl)-indole, a novel allosteric AKT inhibitor, suppresses colon cancer growth in vitro and in vivo. Cancer Prev Res. 2011;4(11):1842-51. doi: 10.1158/1940-6207.CAPR-11-0158. [PubMed: 21885813].
- Yang SM, Tsai KD, Wong HY, Liu YH, Chen TW, Cherng J, et al. Molecular mechanism of Cinnamomum verum component cuminaldehyde inhibits cell growth and induces cell death in human lung squamous cell carcinoma NCI-H520 cells in vitro and in vivo. J Cancer. 2016;7(3):251-61. doi: 10.7150/jca.13689. [PubMed: 26918037].
- Ping J, Gao AM, Qin HQ, Wei XN, Bai J, Liu L, et al. Indole-3-carbinol enhances the resolution of rat liver fibrosis and stimulates hepatic stellate cell apoptosis by blocking the inhibitor of kappaB kinase alpha/inhibitor of kappaB-alpha/nuclear factor-kappaB pathway. J Pharmacol Exp Ther. 2011;339(2):694-703. doi: 10.1124/jpet.111.179820. [PubMed: 21862660].
- Wu P, Shi KJ, An JJ, Ci YL, Li F, Hui KY, et al. The LEF1/CYLD axis and cIAPs regulate RIP1 deubiquitination and trigger apoptosis in selenite-treated colorectal cancer cells. Cell Death Dis. 2014;5(2):e1085. doi: 10.1038/cddis.2014.13. [PubMed: 24577083].
- Li B, Cong M, Zhu Y, Xiong Y, Jin W, Wan Y, et al. Indole-3-carbinol induces apoptosis of hepatic stellate cells through K63 de-ubiquitination of RIP1 in rats. Cell Physiol Biochem. 2017;41(4):1481-90. doi: 10.1159/000470650. [PubMed: 28395284].
- Sun X, Bao J, Nelson KC, Li KC, Kulik G, Zhou X. Systems modeling of anti-apoptotic pathways in prostate cancer: psychological stress triggers a synergism pattern switch in drug combination therapy. PLoS Comput Biol. 2013;9(12):e1003358. doi: 10.1371/journal.pcbi.1003358. [PubMed: 24339759].
- Zhang X, Bi L, Ye Y, Chen J. Formononetin induces apoptosis in PC-3 prostate cancer cells through enhancing the Bax/Bcl-2 ratios and regulating the p38/Akt pathway. Nutr Cancer. 2014;66(4):656-61. doi: 10.1080/01635581.2014.894098. [PubMed: 24666255].
', './data/ircmj/coversheet/cover_en.jpg'))