Journal of Ilam University of Medical Sciences
مجله دانشگاه علوم پزشکی ایلام
J. Ilam Uni. Med. Sci.
Medical Sciences
http://sjimu.medilam.ac.ir
96
journal96
1563-4728
2588-3135
doi
fa
jalali
1401
9
1
gregorian
2022
12
1
30
5
online
1
fulltext
fa
اثر سیلیمارین بر مسیر میتوفاژی در سلولهای سرطانی کولون انسانی HT-29
Silymarin Effect on Mitophagy Pathway in the Human Colon Cancer HT-29 Cells
فارماکولوژی
pharmacology
پژوهشي
Research
<span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Calibri",sans-serif"><b><span lang="FA" style="font-size:9.0pt"><span style="font-family:"B Zar"">مقدمه</span></span></b><b><span lang="AR-SA" style="font-size:9.0pt"><span style="background:white"><span style="font-family:"B Zar""><span style="color:black"><span style="letter-spacing:.1pt">:</span></span></span></span></span></b> <span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar"">آثار ضدسرطانی سیلیمارین در مطالعات متعددی گزارششده است. با وجود این، سازوکار اثر آن در سلولهای سرطانی کولون بهدرستی شناختهنشده است. در این مطالعه اثر سیلیمارین بر مسیر میتوفاژی و ایجاد گونه­های آزاد اکسیژن (</span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">ROS</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar"">) در سلولهای سرطانی کولون انسانی (</span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">HT-29</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar"">) بررسیشده است.</span></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:"Calibri",sans-serif"><b><span lang="FA" style="font-size:9.0pt"><span style="font-family:"B Zar""><span style="color:black"><span style="letter-spacing:.1pt">مواد و روش ها:</span></span></span></span></b> <span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar"">سلولهای سرطانی </span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">HT-29</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar""> و سلولهای غیرسرطانی </span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">NIH-3T3</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar""> به مدت 48 ساعت در معرض غلظتهای 0 (کنترل)، 25، 50 و 100 میکروگرم بر میلیلیتر سیلیمارین قرار گرفتند. درصد زنده­مانی سلولها، سطح </span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">ROS</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar"">، پتانسیل غشای میتوکندری (</span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">MMP</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar"">) و بیان ژنهای مهم مسیر میتوفاژی شامل </span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">Pink1</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar""> (</span></span><i><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">PTEN</span></span></i><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">-induced putative kinase protein 1</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar"">)</span></span> <span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar""> و </span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">Parkin</span></span><span style="font-size:9.0pt"><span style="font-family:"B Zar""> برای ارزیابی آثار سیلیمارین بررسی گردید.</span></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:"Calibri",sans-serif"><b><span lang="FA" style="font-size:9.0pt"><span style="font-family:"B Zar""><span style="color:black"><span style="letter-spacing:-.1pt">یافتهها:</span></span></span></span></b> <span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar"">سیلیمارین بهصورت وابسته به غلظت، درصد زنده­مانی سلولهای </span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">HT-29</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar""> را بهطور معنیداری کاهش داد (</span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">P<0.05</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar"">)؛ همچنین سیلیمارین بهصورت وابسته به غلظت، سبب کاهش معنیداری </span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">MMP</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar""> شد، درحالیکه تشکیل </span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">ROS</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar""> را در سلولهای</span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif"> HT-29 </span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar"">بهطور معنیداری افزایش داد (</span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">P<0.05</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar"">). علاوه بر این، سیلیمارین بیان ژنهای </span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">Pink1</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar""> و </span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">Parkin</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar""> را بهطور معنیداری و بهصورت وابسته به غلظت افزایش داد</span></span> <span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar"">(</span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">P<0.05</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar"">). غلظت 100 میکروگرم بر میلیلیتر سیلیمارین بیشترین تأثیر را در کاهش درصد زنده­مانی و </span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">MMP</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar""> و همچنین افزایش سطح </span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">ROS</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar""> و بیان ژنهای مرتبط با میتوفاژی داشت (</span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">P<0.001</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar"">).</span></span> <span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar"">سیلیمارین در غلظتهای مختلف تغییر معنیداری در درصد زنده­مانی، سطح </span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">ROS</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar""> و </span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">MMP</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar""> در سلولهای غیرسرطانی </span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">NIH-3T3</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar""> ایجاد نکرد.</span></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:"Calibri",sans-serif"><b><span lang="FA" style="font-size:9.0pt"><span style="font-family:"B Zar""><span style="color:black"><span style="letter-spacing:-.1pt">بحث و نتیجهگیری:</span></span></span></span></b> <span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar"">داده­های این مطالعه نشان می­دهند که سیلیمارین احتمالاً با کاهش </span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">MMP</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar"">، سبب افزایش سطح </span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">ROS</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar""> و درنتیجه، القای میتوفاژی از طریق مسیر سیگنالینگ </span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">Pink1</span></span> <span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">/</span></span> <span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">Parkin</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar""> در سلولهای </span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">HT-29</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar""> می­شود</span></span><span dir="LTR" style="font-size:8.0pt"><span style="font-family:"Times New Roman",serif">.</span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="font-family:"B Zar""></span></span></span></span></span></span></span><br>
<br>
<span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:"Calibri",sans-serif"><b><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black"><span style="letter-spacing:-.2pt">Introduction:</span></span></span></span></b> <span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.2pt">The anti-cancer effects of silymarin have been reported in several studies. However, the mechanism of its action in colon cancer cells is not well understood. This study aimed to investigate the effect of silymarin on the mitophagy pathway and the formation of reactive oxygen species (ROS) in human colon cancer cells (HT-29).</span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:"Calibri",sans-serif"><b><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black"><span style="letter-spacing:-.2pt">Material & Methods:</span></span></span></span></b> <span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.2pt">HT-29 cancer cells and NIH-3T3 non-cancer cells were exposed to 0 (control), 25, 50, and 100 μg/ml of silymarin for 48 h. Cell viability, ROS level, mitochondrial membrane potential (MMP), and expression of important mitophagy-related genes including Pink1</span></span></span> <span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.2pt">(</span></span></span><i><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.2pt">PTEN</span></span></span></i><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.2pt">-induced putative kinase protein 1) and Parkin were examined to evaluate the effects of silymarin.</span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:"Calibri",sans-serif"><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif">(Ethic code: </span></span><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif">IR. AJUMS. CMRC-9503</span></span><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif">)</span></span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:"Calibri",sans-serif"><b><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black"><span style="letter-spacing:-.2pt">Findings:</span></span></span></span></b> <span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.2pt">Silymarin significantly reduced the </span></span></span><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.2pt">viability</span></span></span><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.2pt"> percentage of the HT-29 cells depending on the concentration (P<0.05). It also significantly decreased MMP in a concentration-dependent manner while significantly increased ROS formation in the HT-29 cells (P<0.05). In addition, silymarin significantly increased the expression of Pink1 and Parkin genes in a concentration-dependent manner (P<0.05). Concentration of 100 μg/ml of silymarin had the greatest effect on reducing </span></span></span><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.2pt">viability</span></span></span><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.2pt"> and MMP, as well as increasing ROS levels and expression of mitophagy-related genes (P<0.001). Silymarin did not cause significant changes in the </span></span></span><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.2pt">viability</span></span></span><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.2pt"> percentage, ROS level, and MMP of the </span></span></span><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.2pt">NIH-3T3</span></span></span><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.2pt"> non-cancerous cells at different concentrations.</span></span></span><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.2pt"></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:"Calibri",sans-serif"><b><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black"><span style="letter-spacing:-.2pt">Discussion & </span></span></span></span></b><b><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.2pt">Conclusion:</span></span></span></b> <span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.2pt">According to the results, silymarin increases the level of ROS by decreasing MMP, thereby inducing mitophagy through the Pink1/Parkin signaling pathway in the HT-29 cells.</span></span></span><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.2pt"></span></span></span></span></span></span><br>
میتوفاژی, سرطان کولون, میتوکندری, سیلیمارین
Colon cancer, Mitochondria, Mitophagy, Silymarin
14
23
http://sjimu.medilam.ac.ir/browse.php?a_code=A-10-7033-1&slc_lang=fa&sid=1
Layasadat
Khorsandi
لعیاسادات
خرسندی
khorsandi_cmrc@yahoo.com
9600319475328460045866
9600319475328460045866
Yes
ellular and Molecular Research Center, Research Institute of Basic Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
مرکز تحقیقات سلولی و مولکولی، پژوهشکده علوم پایۀ پزشکی، دانشگاه علوم پزشکی جندیشاپور اهواز، اهواز، ایران
Maryam
Mombeni
مریم
ممبینی
maryammombeini71@gmail.com
9600319475328460045867
9600319475328460045867
No
Dept of Anatomical Sciences, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
گروه علوم تشریحی، دانشکدۀ پزشکی، دانشگاه علوم پزشکی جندیشاپور اهواز، اهواز، ایران
Ghasem
Saki
قاسم
ساکی
ghasemsaki@yahoo.com
9600319475328460045868
9600319475328460045868
No
Dept of Anatomical Sciences, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
گروه علوم تشریحی، دانشکدۀ پزشکی، دانشگاه علوم پزشکی جندیشاپور اهواز، اهواز، ایران
Neda
Bavarsad
ندا
باورصاد
bavarsad-n@ajums.ac.ir
9600319475328460045869
9600319475328460045869
No
Nanotechnology Research Center, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
مرکز تحقیقات نانوتکنولوژی، دانشکدۀ داروسازی، دانشگاه علوم پزشکی جندیشاپور اهواز، اهواز، ایران