نوع مقاله : مقاله پژوهشی
نویسندگان
1 دانشیار، گروه زیستشناسی، دانشکده علوم، دانشگاه شهید چمران اهواز، اهواز، ایران
2 دانشآموخته دکتری حرفهای دامپزشکی دانشکده دامپزشکی دانشگاه شهیدچمران اهواز، اهواز، ایران
چکیده
زمینه و هدف: در سالهای اخیر، محققان به دلیل فعالیت بیولوژیکی بالاو سمیت کم، بر فعالیت ضدسرطانی کومارین تمرکز کرده اند که میتوانند عوارض جانبی ناشی از پرتودرمانی را خنثی کنند. هدف از مطالعه حاضر، بررسی تأثیرات سیتوتوکسیک کومارین بر سلولهای سرطانی ردههای HT-29 و A549 می باشد.
مواد و روشها: در این مطالعه تجربی، استوک کومارین تهیه و سلولها با غلظتهای 5، 10، 15، 20 و 25 میکرومولار آن تیمار شدند و در روزهای 1، 3 و 5 روز پس از تیمار، بقا و مورفولوژی سلولها ارزیابی شد. غلظت IC50 کومارین با استفاده از روش MTT در دو رده سلولی محاسبه گردید. همچنین بیان ژنهای درگیر درآپوپتوز همچون Bax, Bad و Bcl-2 با روش qRT_PCR ارزیابی شد. یافته ها با استفاده از روش آماری واریانس یکطرفه تحلیل گردید.
یافتهها: نتایج نشان داد که کومارین بهصورت وابسته به دوزو زمان، میزان بقا و تکثیر سلولهای HT-29 و A549 را بهطور معنی-داری (P≤0.001)کاهش میدهد همچنین درصد بقای سلولی در سلولهای تیمارشده در روز پنجم نسبت به گروه کنترل، بهشدت کاهش یافت که نسبت به نمونه های روز اول و سوم هم کاهش معنی دار را نشان داد (P≤0.001). تغییرات موروفولوژی همچون کاهش تراکم سلولی، گردشدن و چروکیدکی سلولها نیز بهطور محسوسی در سلولهای تیمار شده مشاهده شد. همچنین، نتایج مولکولی نشان داد که کومارین توانست سبب افزایش معنی دار بیان ژنهای Bax, Bad و کاهش بیان ژن Bcl-2 گردد که این تغییرات ژنی در سلولهای A549 بهطور معنی داری بیشتر از HT-29 بود.
نتیجهگیری: کومارین قادر است فعالیت ضدتکثیری و القای آپوپتوزی مؤثری در برابر سلولهای سرطانی کولون و ریه داشته باشد.
کلیدواژهها
موضوعات
عنوان مقاله [English]
Evaluation of the Effects of Coumarin on Apoptotic Genes Expression in Lung and Colorectal Cancer Cells
نویسندگان [English]
- elham hoveizi 1
- Kiavash Hushmandi 2
1 Associate Professor, Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
2 Doctor of Veterinary Medicine (Graduated), Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
چکیده [English]
Introduction: In recent years, researchers have considered the anticancer activity coumarins, due to their powerful biological activity and poor toxicity that can neutralize the side effects induced by radiotherapy. The aim of this study was to investigate the cytotoxic effects of coumarin on HT-29 and A549 cancer cells.
Materials and Methods: In this experimental study, the stoke of coumarin was prepared and then for 1,3, and 5 days at concentrations of5, 10, 15, 20, and 25 μM the cells were treated and evaluated on viability days and morphology of the cells indefinite days. The IC50 concentration of coumarin was calculated using MTT assay in two cell lines. Also, the expression of the involved genes in apoptosis such as Bax, Bad, and Bcl-2 was evaluated by the qRT_PCR method. Data were analyzed by a one-way ANOVA test.
Results: The results showed that coumarin reduced the viability and proliferation of HT-29 and special A549 cells by dose and time significantly (P≤0.001), as well as the viability rate of cells in treated cells on the fifth day, significantly decreased compared to the control group (P <0.05). Morphological changes such as reduced chromatin density, cell turnover were also noticeably observed in the cells. Also, molecular results showed that coumarin could significantly increase the expression of Bax, Bad genes and decrease the expression of Bcl-2 gene expression. That these genetic changes in A549 cells were significantly greater than HT-29.
Conclusion: Coumarin is capable of anti-proliferative activity and induces apoptosis effectively against colon and lung cancer cells.
کلیدواژهها [English]
- Apoptosis
- Colorectal cancer
- Coumarin
- Cytotoxicity
- Lung carcinoma
- 1.Xue L. Tao Y. Yuan Y. Qu W. Wang W. Curcumin suppresses renal carcinoma tumorigenesis by regulating circ-FNDC3B/miR-138-5p/IGF2 axis. Anticancer Drugs. 2021;32(7):734-744.
- Taheri A. Ghaffari M. Namavari M. The Effects of Seaweed Gracilaria arcuata Extract on the Stimulation of Apoptosis in Colorectal Cancer Cell Lines. Alborz University Medical Journal. 2018;7(4):281-92.
- Erkasap N. Ozyurt R. Ozkurt M. Yaşar F. Erkasap S. Ihtiyar E. The role of JAK/STAT signaling pathway and TNF-α crosstalk in human colorectal cancer. Gene Reports. 2016; 3:1-4.
- Huang X. Chen C. Xu Y. Shen L. Chen Y. Su H. Infiltrating T-cell abundance combined with EMT-related gene expression as a prognostic factor of colon cancer. Bioengineered. 2021;12(1):2688-2701.
- Quartuccio N. Salem A. Laudicella R. Spataro A. Chiaravalloti A. Caobelli F. Cistaro A. Alongi P. Evangelista L.The role of 18F-Fluorodeoxyglucose PET/CT in restaging patients with small cell lung cancer: a systematic review . Nucl Med Commun. 2021;42(8):839-845.
- Fang T. Liang T. Wang Y. Wu H. Liu S. Xie L. Liang J. Wang C. Tan Y. Prognostic role and clinicopathological features of SMAD4 gene mutation in colorectal cancer: a systematic review and meta-analysis. BMC Gastroenterol. 2021;21(1):297.
- Zaborowski AM. Winter DC. Lynch L.The therapeutic and prognostic implications of immunobiology in colorectal cancer: a review. Br J Cancer. 2021. doi: 10.1038/s41416-021-01475-x.
- Mahdavi M. Laforest-Lapointe I. Masse E. Preventing Colorectal Cancer through Prebiotics. Microorganisms. 2021;9(6):1325.
- Kolahi M. Tabande M. Saremi S. Hossaini SA. Hashemitabar M. The Study of Apoptotic Effect of p-Coumaric Acid on Breast Cancer Cells MCF-7. SSU_Journals. 2016; 24(3): 211-221.
- Xu X. Yan Y. Huang W. Mo T. Wang X. Wang J. Li J. Shi S. Liu X. Tu P. Molecular cloning and biochemical characterization of a new coumarin glycosyltransferase CtUGT1 from Cistanche tubulosa. Fitoterapia. 2021:104995.
- Zhu H. Ying S. Zhou B. Hu X. Liang X. Li W. Wang D. Jin H. Pan Y. Design, synthesis, and evaluation of novel coumarin-dithiocarbamate derivatives (IDs) as anti-colorectal cancer agents. J Enzyme Inhib Med Chem. 2021;36(1):593-604.
- Zhang J. Feng M. Guan W. Naturally occurring aesculetin coumarin exerts antiproliferative effects in gastric cancer cells mediated via apoptotic cell death, cell cycle arrest and targeting PI3K/AKT/M-TOR signalling pathway. Acta Biochim Pol. 2021;68(1):109-113.
- Rafiee Z. Zare Moaiedi M. Valizade Gorji A. Mansouri P-Coumaric Acid Mitigates Doxorubicin-Induced Nephrotoxicity Through Suppression of Oxidative Stress, Inflammation and Apoptosis. Arch Med Res 2020;51(1):32-40.
- Mohammadi A. Vahabzadeh Z. Jamalzadeh S. Khalili T. Trimethylamine-N-oxide, as a risk factor for atherosclerosis, induces stress in J774A.1 murine macrophages. Adv Med Sci 2018; 63(1):57-63.
- Shafie A. Moradi F. Izadpanah E. Mokarizadeh A. Moloudi MR. Nikzaban M. Hassanzadeh K. Neuroprotection of donepezil against morphine-induced apoptosis is mediated through Toll-like receptors. Eur J Pharmacol 2015; 764:292-7.
- Sain A. Kandasamy T. Naskar D. In silico approach to target PI3K/Akt/mTOR axis by selected Olea europaea phenols in PIK3CA mutant colorectal cancer. J Biomol Struct Dyn. 2021:1-16.
- Jiang D. Xu J. Liu S. Nasser MI. Wei W. Mao T. Liu X. Zou X. Li J. Li X. Basnet P. Skalko-Basnet N. Rosmanol induces breast cancer cells apoptosis by regulating PI3K/AKT and STAT3/JAK2 signaling pathways Oncol Lett. 2021;22(2):631.
- Obeng E. Apoptosis (programmed cell death) and its signals - A review. Braz J Biol. 2021;81(4):1133-1143.
- Mohamadi T. Hoveizi E. Comparison of antiproliferative effect of cinnamon (Cinnamomum zeylanicum) hydroalcoholic extract with cyclophosphamide medicine on A459 Cancer Cells." Razi Journal of Medical Sciences. 2018; 25(167): 211-29.
- Mazarie A. Mousavi-Nik SM. Fahmideh L. Assessments of phenolic, flavonoid and antioxidant activity of aqueous, alcoholic, methanol and acetone extracts of thirteen medicinal plants. Nova Biologica Rep. 2018; 4: 299-30.
- Saboormaleki S. Sadeghian H. Bahrami AR. Orafaie A. Matin MM. 7-Farnesyloxycoumarin exerts anti-cancer effects on a prostate cancer cell line by 15-LOX-1 inhibition. Archives of Iranian Medicine. 2018; 21.6: 251-259.
- Ragab FA. Eissa AAM. Fahim SH. Salem MA. Gamal MA, Nissan YM. Synthesis and biological evaluation of new coumarin derivatives as cytotoxic agents. Arch Pharm 2021. doi: 10.1002/ardp.202100029.
- Haghighi F. Matin M. Bahrami AR. Iranshahi M. Investigation of cytotoxicity and anti-cancer effects of 7-isopentenyloxycoumarin in vitro. Molecular Aspects of Cancer. 2010; 1:12-20.
- Kędzierska-Matysek M. Stryjecka M. Teter A. Skałecki P. Domaradzki P. Florek M. Relationships between the Content of Phenolic Compounds and the Antioxidant Activity of Polish Honey Varieties as a Tool for Botanical Discrimination. Molecules. 2021; 26(6):1810.
- Liu, MM. Chen XY, Huang YQ, Feng P. Guo YL. Yang G. Chen Y. Hybrids of Phenylsulfonylfuroxan and Coumarin as Potent Antitumor Agents. J. Med. Chem. 2015; 57, 9343-9356.
- Wang, Q. A hybrid of coumarin and phenylsulfonylfuroxan induces caspase-dependent apoptosis and cytoprotective autophagy in lung adenocarcinoma cells. Phytomedicine. 2018; 29: 160-167.