Medical Sciences Journal of Islamic Azad University
فصلنامه علوم پزشکی دانشگاه آزاد اسلامی تهران
MEDICAL SCIENCES
Medical Sciences
http://tmuj.iautmu.ac.ir
1
admin
1023-5922
2008-3386
000
10.61882/iau
000
1023-5922
000
fa
jalali
1400
12
1
gregorian
2022
3
1
32
1
online
1
fulltext
fa
اثرات کوچکمولکول GW9508 بر آنزیمهای استرس اکسیداتیو در سلولهای سرطانی کولون و سلول های غیرسرطانی HUVEC
Effects of GW9508 small molecule on oxidative stress enzymes in colorectal cancer and non-cancerous HUVEC cells
زيست شناسي جانوري
Animal Biology
تجربي
Experimental
<span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman",serif"><span style="font-weight:bold"><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin"">سابقه و هدف</span></span><i><span lang="FA" style="font-size:12.0pt"><span style="font-family:Nazanin"><span style="font-weight:normal">:</span></span></span></i> <i><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="font-weight:normal">هدف از مطالعه حاضر بررسی اثرات کوچک مولکول </span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="font-weight:normal">GW9508</span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="font-weight:normal"> به عنوان یک اسید چرب غیراشباع بر تولید استرس اکسیداتیو و افزایش فعالیت آنزیمهای استرس اکسیداتیو در سلولهای سرطانی </span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="font-weight:normal">HT-29</span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="font-weight:normal"> و سلول­های غیرسرطانی </span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="font-weight:normal">HUVEC</span></span></i><i> </i><i><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="font-weight:normal">بود</span></span></span></i><i><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="font-weight:normal">. </span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="font-weight:normal"></span></span></i></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman",serif"><span style="font-weight:bold"><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.3pt">روش بررسی</span></span></span><i><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.3pt"><span style="font-weight:normal">:</span></span></span></span></i> <i><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal">اثرات </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">GW9508</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> برتوان زیستی سلولها در روزهای ۱، ۳ و ۵ پس از تیمار با روش </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">MTT</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> بررسی شد. از سنجش آنزیمهای سوپراکسید دیسموتاز (</span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">SOD</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal">) و کاتالاز برای بررسی استرس اکسیداتیو استفاده شد. همچنین بررسی تغییرات سلول و هسته­ها، با استفاده از میکروسکوپ اینورت و رنگآمیزی دپی انجام شد.</span></span></span></span></i><i> </i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.3pt"><span style="font-weight:normal"></span></span></span></i></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman",serif"><span style="font-weight:bold"><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt">یافته </span></span></span><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt">ها:</span></span></span> <i><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal">غلظت </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">IC50</span></span></span></i><i> </i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">GW9508</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> در هر دو رده سلول سرطانی و نرمال </span></span></span></span></i><i><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal">۵۰۰</span></span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> میکرومولار ارزیابی شد. نتایج سنجش فعالیت آنزیمی نشان داد که افزایش فعالیت کاتالاز و </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">SOD</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> در سلولهای تیمار یافته سبب پیشبرد آپوپتوز در این سلول­ها گردید. میزان فعالیت </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">SOD</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> و کاتالاز</span></span></span></span></i><i><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> در سلولهای </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">HT-29</span></span></span></i><i><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> تیماریافته به ترتیب</span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">mU/mg </span></span></span></i><i><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal">۲۵۴/۱ و ۳۳۸/۰ ارزیابی شد که نسبت به فعالیت این دو آنزیم در گروه کنترل منفی سلولهای سرطانی ( </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">mU/mg </span></span></span></i><i><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal">۸۵/۰ و ۲۰۶/۰) به طور معنیداری افزایش یافت (05/0</span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">p≤</span></span></span></i><i><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal">). همچنین افزایش معنیدار فعالیت </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">SOD</span></span></span></i><i><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> و کاتالاز در سلولهای تحت تیمار </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">HUVEC</span></span></span></i><i><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> (</span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">mU/mg </span></span></span></i><i><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal">۱۱۱/۱ و ۵۱۷/۰) نسبت به فعالیت این دو آنزیم در گروه کنترل به ترتیب </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">mU/mg </span></span></span></i><i><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal">۷۵۵/۰ و ۱۸۴/۰ محاسبه شد.</span></span></span></span></i></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman",serif"><span style="font-weight:bold"><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin"">نتیجه </span></span><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin"">گیری</span></span><i><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="font-weight:normal">:</span></span></span></i> <i><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal">کوچک مولکول </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">GW9508</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> با القای استرس اکسیداتیو و تولید </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">ROS</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> در سلولهای </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">HT-29</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> و </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">HUVEC</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal">، سبب سمیت و در نتیجه پیشبرد مرگ سلولی آپوپتوزی در سلولهای سرطانی میشود. با این حال این اثر وابسته به دوز و نوع</span></span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> رده سلولی است</span></span></span></span></i><i><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="letter-spacing:-.2pt"><span style="font-weight:normal">.</span></span></span></span></i><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Koodak""><span style="font-weight:normal"></span></span></span></span></span></span></span></span></span><br>
<span style="font-size:12pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:11.0pt"><span style="font-family:"Times New Roman",serif"><b><span style="font-size:11.0pt">Background</span></b><span style="font-size:11.0pt">: </span><span lang="EN-GB" style="font-size:11.0pt">In this study, we aimed to evaluate the effects of GW9508 as an unsaturated fatty acid on inducing oxidative stress </span><span style="font-size:11.0pt">in</span><span lang="EN-GB" style="font-size:11.0pt"> HT-29 cancer cell line and non-cancer HUVEC cells</span><span style="font-size:11.0pt">. </span></span></span></span></span></span><br>
<span style="font-size:12pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:11.0pt"><span style="font-family:"Times New Roman",serif"><b><span style="font-size:11.0pt">Materials and methods</span></b><span style="font-size:11.0pt">: The effects of GW9508 on cell viability were determined by performing MTT assay after 1, 3 and 5 days.</span><span lang="EN-GB" style="font-size:11.0pt"> The anti-oxidant superoxide dismutase (SOD) and catalase enzymes' assay was performed to evaluate the apoptosis. Moreover, inverted microscope and DAPI staining were applied to measure the changes in cell and nucleus morphology</span><span style="font-size:11.0pt">. </span></span></span></span></span></span><br>
<span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="line-height:11.0pt"><span style="font-family:"Times New Roman",serif"><b><span style="font-size:11.0pt">Results</span></b><span style="font-size:11.0pt">: The <i>IC50</i> dose of GW9508 was 500 µM in both cancer and normal cells. Results of enzymatic activity assay exhibited the increscent of activity of catalase and </span><span lang="EN-GB" style="font-size:11.0pt">SOD in treated cells </span><span style="font-size:11.0pt">led</span><span lang="EN-GB" style="font-size:11.0pt"> to promoting apoptosis in cells. </span><span style="font-size:11.0pt">The amount of activities of </span><span lang="EN-GB" style="font-size:11.0pt">SOD and catalase in HT-29 treated cells that </span><span style="font-size:11.0pt">were </span><span lang="EN-GB" style="font-size:11.0pt">calculated 1.254 and 0.338 </span><span style="font-size:11.0pt">mU/mg </span><span lang="EN-GB" style="font-size:11.0pt">respectively, which had </span><span style="font-size:11.0pt">a significant increase compared to activities of these two enzymes in control cells (0.85 and 0.206 mU/mg, </span><span lang="EN-GB" style="font-size:11.0pt">respectively) </span><span style="font-size:11.0pt">(p≤0.05)</span><span lang="EN-GB" style="font-size:11.0pt">. There was also a significant increase in the activities of SOD and catalase in HUVEC treated cells (1.111 and 0.517 </span><span style="font-size:11.0pt">mU/mg</span><span lang="EN-GB" style="font-size:11.0pt">) compared to the activities of the two enzymes in the control group, which were calculated 0.755 and 0.184 </span><span style="font-size:11.0pt">mU/mg</span><span lang="EN-GB" style="font-size:11.0pt">, respectively</span><span style="font-size:11.0pt">.</span></span></span></span></span><br>
<span style="font-size:12pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:11.0pt"><span style="font-family:"Times New Roman",serif"><b><span style="font-size:11.0pt">Conclusion</span></b><span style="font-size:11.0pt">: </span><span lang="EN-GB" style="font-size:11.0pt">GW9508 small molecule induces oxidative stress and ROS production in HT-29 and HUVEC cells,</span> <span lang="EN-GB" style="font-size:11.0pt">leading to cytotoxicity and thus promoting apoptotic cell death in cancer cells. However, these effects are contingent upon dose and the type of cell lineages</span><span style="font-size:11.0pt">.</span></span></span></span></span></span><br>
سرطان کلورکتال, اسید های چرب غیر اشباع, کوچک مولکول, استرس اکسیداتیو
Colorectal cancer, Unsaturated fatty acid, Small molecule, Oxidative stress
31
43
http://tmuj.iautmu.ac.ir/browse.php?a_code=A-10-323-5&slc_lang=fa&sid=1
Behnoosh
Rafienia
بهنوش
رفیعی نیا
behnoosh.rafiei@gmail.com
100319475328460010122
100319475328460010122
No
Student, Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
دانشجو، گروه زیست شناسی، دانشکده علوم، دانشگاه شهید چمران اهواز، اهواز، ایران
Elham
Hoveizi
الهام
حویزی
e.hoveizi@yahoo.com
100319475328460010123
100319475328460010123
Yes
Associate Professor, Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
دانشیار، گروه زیست شناسی، دانشکده علوم، دانشگاه شهید چمران اهواز، اهواز، ایران
Ali
Shahriari
علی
شهریاری
alishhrr@yahoo.com
100319475328460010124
100319475328460010124
No
Associate Professor, Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Iran
دانشیار، گروه بیوشیمی و بیولوژی مولکولی، دانشکده دامپزشکی، دانشگاه شهید چمران اهواز، اهواز، ایران