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Ghodousi-Dehnavi E, Arjmand M, Akbari Z, Aminzadeh Bukani M, Haji Hosseini R. Anti-Cancer Effect of Dorema Ammoniacum Gum by Targeting Metabolic Reprogramming by Regulating APC, P53, KRAS Gene Expression in HT-29 Human Colon Cancer Cells. rbmb.net 2023; 12 (1) :127-135
URL: http://rbmb.net/article-1-1130-en.html
URL: http://rbmb.net/article-1-1130-en.html
Elham Ghodousi-Dehnavi 
, Mohammad Arjmand * , Ziba Akbari , Mansour Aminzadeh Bukani , Reza Haji Hosseini
, Mohammad Arjmand * , Ziba Akbari , Mansour Aminzadeh Bukani , Reza Haji Hosseini
Metabolomics Lab. Department of Biochemistry, Pasteur Institute of Iran, Pasteur Avenue, Tehran, Iran.
Abstract: (1353 Views)
Background: Colorectal cancer is a heterogeneous disease that leads to metabolic disorders due to multiple upstream genetic and molecular changes and interactions. The development of new therapies, especially herbal medicines, has received much global attention. Dorema ammoniacum is a medicinal plant. Its gum is used in healing known ailments. Studying metabolome profiles based on nuclear magnetic resonance 1HNMR as a non-invasive and reproducible tool can identify metabolic changes as a reflection of intracellular fluxes, especially in drug responses.
This study aimed to investigate the anti-cancer effects of different gum extracts on metabolic changes and their impact on gene expression in HT-29 cell.
Methods: Extraction of Dorema ammoniacum gum with hexane, chloroform, and dichloromethane organic solvents was performed. Cell inhibition growth percentage and IC50 were assessed. Following treating the cells with dichloromethane extract, p53, APC, and KRAS gene expression were determined. 1HNMR spectroscopy was conducted. Eventually, systems biology software tools interpreted combined metabolites and genes simultaneously.
Results: The lowest determined IC50 concentration was related to dichloromethane solvent, and the highest was hexane and chloroform. The expression of the KRAS oncogene gene decreased significantly after treatment with dichloromethane extract compared to the control group, and the expression of tumor suppressor gene p53 and APC increased significantly. Most gene-altered convergent metabolic phenotypes.
Conclusions: This study's results indicate that the dichloromethane solvent of Dorema ammoniacum gum exhibits its antitumor properties by altering the expression of genes involved in HT-29 cells and the consequent change in downstream metabolic reprogramming.
This study aimed to investigate the anti-cancer effects of different gum extracts on metabolic changes and their impact on gene expression in HT-29 cell.
Methods: Extraction of Dorema ammoniacum gum with hexane, chloroform, and dichloromethane organic solvents was performed. Cell inhibition growth percentage and IC50 were assessed. Following treating the cells with dichloromethane extract, p53, APC, and KRAS gene expression were determined. 1HNMR spectroscopy was conducted. Eventually, systems biology software tools interpreted combined metabolites and genes simultaneously.
Results: The lowest determined IC50 concentration was related to dichloromethane solvent, and the highest was hexane and chloroform. The expression of the KRAS oncogene gene decreased significantly after treatment with dichloromethane extract compared to the control group, and the expression of tumor suppressor gene p53 and APC increased significantly. Most gene-altered convergent metabolic phenotypes.
Conclusions: This study's results indicate that the dichloromethane solvent of Dorema ammoniacum gum exhibits its antitumor properties by altering the expression of genes involved in HT-29 cells and the consequent change in downstream metabolic reprogramming.
Type of Article: Original Article |
Subject:
Biochemistry
Received: 2023/01/16 | Accepted: 2023/02/16 | Published: 2023/08/15
Received: 2023/01/16 | Accepted: 2023/02/16 | Published: 2023/08/15
References
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. [DOI:10.3322/caac.21492] [PMID]
2. Bayatiani MR, Ahmadi A, Aghabozorgi R, Seif F. Concomitant Up-Regulation of Hsa- Mir-374 and Down-Regulation of Its Targets, GSK-3beta and APC, in Tissue Samples of Colorectal Cancer. Rep Biochem Mol Biol. 2021;9(4):408-16. [DOI:10.52547/rbmb.9.4.408] [PMID] [PMCID]
3. Chen HJ, Wei Z, Sun J, Bhattacharya A, Savage DJ, Serda R, et al. A recellularized human colon model identifies cancer driver genes. Nat Biotechnol. 2016;34(8):845-51. [DOI:10.1038/nbt.3586] [PMID] [PMCID]
4. Cancer Genome Atlas N. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487(7407):330-7. [DOI:10.1038/nature11252] [PMID] [PMCID]
5. Bakhtiarian A, Shojaii A, Hashemi S, Nikoui V. Evaluation of Analgesic and Anti-Inflammatory Activity of Dorema Ammoniacum Gum in Animal Model. Int J Pharm Sci Res. 2017;8(7):3102-6.
6. Mazaheritehrani M, Hosseinzadeh R, Mohadjerani M, Tajbakhsh M, Ebrahimi SN. Acetylcholinesterase Inhibitory Activity of Dorema Ammoniacum Gum Extracts and Molecular Docking Studies. Int J Pharm Sci Res. 2020;11(2):637-44.
7. Adhami HR, Lutz J, Kählig H, Zehl M, Krenn L. Compounds from gum ammoniacum with acetylcholinesterase inhibitory activity. Sci Pharm. 2013;81(3):793-805. [DOI:10.3797/scipharm.1306-16] [PMID] [PMCID]
8. Ramola B, Kumar V, Nanda M, Mishra Y, Tyagi T, Gupta A, Sharma N. Evaluation, comparison of different solvent extraction, cell disruption methods and hydrothermal liquefaction of Oedogonium macroalgae for biofuel production. Biotechnol Rep (Amst). 2019;22:e00340. [DOI:10.1016/j.btre.2019.e00340] [PMID] [PMCID]
9. Chahardehi AM, Arsad H, Ismail NZ, Lim V. Low cytotoxicity, and antiproliferative activity on cancer cells, of the plant Senna alata (Fabaceae). Rev De Biol Trop. 2021;69(1):317-30. [DOI:10.15517/rbt.v69i1.42144]
10. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1-2):55-63. [DOI:10.1016/0022-1759(83)90303-4] [PMID]
11. Raeisossadati R, Abbaszadegan MR, Moghbeli M, Tavassoli A, Kihara AH, Forghanifard MM. Aberrant expression of DPPA2 and HIWI genes in colorectal cancer and their impacts on poor prognosis. Tumour Biol. 2014;35(6):5299-305. [DOI:10.1007/s13277-014-1690-x] [PMID]
12. Lodi A, Ronen SM. Magnetic resonance spectroscopy detectable metabolomic fingerprint of response to antineoplastic treatment. PLoS One. 2011;6(10):e26155. [DOI:10.1371/journal.pone.0026155] [PMID] [PMCID]
13. Ahmadi M, Akhbari Z, Zamani Z, Hajhossieni R, Arjmand M. Study the Mechanism of Antileishmanial Action of Xanthium strumarium Against Amastigotes Stages in Leishmania major: A Metabolomics Approach. Jundishapur J Nat Pharm Prod. 2021;16(3). [DOI:10.5812/jjnpp.106431]
14. Park SG, Schimmel P, Kim S. Aminoacyl tRNA synthetases and their connections to disease. Proc Natl Acad Sci USA. 2008;105(32):11043-9. [DOI:10.1073/pnas.0802862105] [PMID] [PMCID]
15. D'Hulst G, Soro-Arnaiz I, Masschelein E, Veys K, Fitzgerald G, Smeuninx B, et al. PHD1 controls muscle mTORC1 in a hydroxylation-independent manner by stabilizing leucyl tRNA synthetase. Nat commun. 2020;11(1):174. [DOI:10.1038/s41467-019-13889-6] [PMID] [PMCID]
16. Zhou Z, Sun B, Huang SQ, Yu DS, Zhang XC. Roles of aminoacyl-tRNA synthetase-interacting multi-functional proteins in physiology and cancer. Cell Death Dis. 2020;11(7):579. [DOI:10.1038/s41419-020-02794-2] [PMID] [PMCID]
17. Nam SH, Kim D, Lee M-S, Lee D, Kwak TK, Kang M, et al. Noncanonical roles of membranous lysyl-tRNA synthetase in transducing cell-substrate signaling for invasive dissemination of colon cancer spheroids in 3D collagen I gels. Oncotarget. 2015;6(25):21655-74. [DOI:10.18632/oncotarget.4130] [PMID] [PMCID]
18. Park B-J, Kang JW, Lee SW, Choi S-J, Shin YK, Ahn YH, et al. The haploinsufficient tumor suppressor p18 upregulates p53 via interactions with ATM/ATR. Cell. 2005;120(2):209-21. [DOI:10.1016/j.cell.2004.11.054] [PMID]
19. Wang ZP, Tian Y, Lin J. Role of wild-type p53-induced phosphatase 1 in cancer. Oncol Lett. 2017;14(4):3893-8. [DOI:10.3892/ol.2017.6685] [PMID] [PMCID]
20. Zhong L, Zhang Y, Yang J-Y, Xiong L-F, Shen T, Sa YL, et al. Expression of IARS2 gene in colon cancer and effect of its knockdown on biological behavior of RKO cells. Int J Clin Exp Pathol. 2015;8(10):12151-9.
21. Kurmi K, Haigis MC. Nitrogen Metabolism in Cancer and Immunity. Trends Cell Biol. 2020;30(5):408-24. [DOI:10.1016/j.tcb.2020.02.005] [PMID] [PMCID]
22. Li L, Mao Y, Zhao L, Li L, Wu J, Zhao M, et al. p53 regulation of ammonia metabolism through urea cycle controls polyamine biosynthesis. Nature. 2019;567(7747):253-6. [DOI:10.1038/s41586-019-0996-7] [PMID]
23. Toda K, Kawada K, Iwamoto M, Inamoto S, Sasazuki T, Shirasawa S, et al. Metabolic Alterations Caused by KRAS Mutations in Colorectal Cancer Contribute to Cell Adaptation to Glutamine Depletion by Upregulation of Asparagine Synthetase. Neoplasia. 2016;18(11):654-65. [DOI:10.1016/j.neo.2016.09.004] [PMID] [PMCID]
24. Hutton JE, Wang X, Zimmerman LJ, Slebos RJ, Trenary IA, Young JD, et al. Oncogenic KRAS and BRAF Drive Metabolic Reprogramming in Colorectal Cancer. Mol Cell Proteomics. 2016;15(9):2924-38. [DOI:10.1074/mcp.M116.058925] [PMID] [PMCID]
25. Suzuki S, Tanaka T, Poyurovsky MV, Nagano H, Mayama T, Ohkubo S, et al. Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species. Proc Natl Acad Sci USA. 2010;107(16):7461-6. [DOI:10.1073/pnas.1002459107] [PMID] [PMCID]
26. Brown RE, Short SP, Williams CS. Colorectal Cancer and Metabolism. Curr Colorectal Cancer Rep. 2018;14(6):226-41. [DOI:10.1007/s11888-018-0420-y] [PMID] [PMCID]
27. Xue P, Zeng F, Duan Q, Xiao J, Liu L, Yuan P, et al. BCKDK of BCAA Catabolism Cross-talking With the MAPK Pathway Promotes Tumorigenesis of Colorectal Cancer. EBioMedicine. 2017;20:50-60. [DOI:10.1016/j.ebiom.2017.05.001] [PMID] [PMCID]
28. Tian Q, Yuan P, Quan C, Li M, Xiao J, Zhang L, et al. Phosphorylation of BCKDK of BCAA catabolism at Y246 by Src promotes metastasis of colorectal cancer. Oncogene. 2020;39(20):3980-96. [DOI:10.1038/s41388-020-1262-z] [PMID] [PMCID]
29. Yoshie T, Nishiumi S, Izumi Y, Sakai A, Inoue J, Azuma T, Yoshida M. Regulation of the metabolite profile by an APC gene mutation in colorectal cancer. Cancer Sci. 2012;103(6):1010-21. [DOI:10.1111/j.1349-7006.2012.02262.x] [PMID] [PMCID]
30. Makia R, Al-Sammarrae K, Al-Halbosiy M, Al-Mashhadani M. In Vitro Cytotoxic Activity of Total Flavonoid from Equisetum Arvense Extract. Rep Biochem Mol Biol. 2022;11(3):487-92. [DOI:10.52547/rbmb.11.3.487] [PMID] [PMCID]
31. Deng L, Yao P, Li L, Ji F, Zhao S, Xu C, et al. p53- mediated control of aspartate- asparagine homeostasis dictates LKB1 activity and modulates cell survival. Nat Commun. 2020;11(1):1755. [DOI:10.1038/s41467-020-15573-6] [PMID] [PMCID]
32. Gwinn DM, Lee AG, Briones-Martin-Del-Campo M, Conn CS, Simpson DR, Scott AI, et al. Oncogenic KRAS Regulates Amino Acid Homeostasis and Asparagine Biosynthesis via ATF4 and Alters Sensitivity to L-Asparaginase. Cancer Cell. 2018;33(1):91-107 e6. [DOI:10.1016/j.ccell.2017.12.003] [PMID] [PMCID]
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