بررسی خاصیت ضدسرطانی پپتید HL-7 از طریق تغییر در بیان ژن Fas، کاسپاز 8 و کاسپاز ۳
الموضوعات :
زهرا ستایش مهر
1
(استادیار، گروه زیست‌شناسی، دانشکده علوم، دانشگاه زابل، زابل، ایران)
حسین کمال الدینی
2
(استادیار، گروه زیست‌شناسی، دانشکده علوم، دانشگاه زابل، زابل، ایران)
محمد حاجی تبار
3
(کارشناسی ارشد، گروه زیست‌شناسی، دانشکده علوم، دانشگاه زابل، زابل، ایران)
تاريخ الإرسال : 29 الجمعة , شوال, 1444
تاريخ التأكيد : 10 الجمعة , محرم, 1445
تاريخ الإصدار : 01 الجمعة , شوال, 1444
الکلمات المفتاحية:
پپتید,
سرطان,
دهانه رحم,
Hela,
HL-7,
آپپتوز,
کاسپاز ۳,
بیان ژن Fas,
کاسپاز 8,
ملخص المقالة :
هدف: سرطان دهانه رحم، عامل مهمی در مرگ و میر زنان در سراسر جهان است. نتایج به‌دست آمده تا به‌امروز، بیانگر دخالت پپتیدهای فعال زیستی در درمان سرطان است. در این راستا، هدف پژوهش حاضر بررسی خاصیت ضدسرطانی پپتید HL-7 از طریق تغییر در بیان ژن Fas، کاسپاز 8 و کاسپاز ۳ است.مواد و روش‌ها: در این مطالعه، زیست‌پذیری سلول‌های سرطانی دهانه رحم تیمار شده با پپتید HL-7 در دو غلظت 45 و 60 میکرومولار در دو زمان 12 و 24 ساعت، با استفاده از سنجش MTT بررسی شد. همچنین بیان ژن‌های Fas، کاسپاز 8 و کاسپاز ۳ در سطح mRNA و پروتئین، به‌ترتیب، با استفاده از روش‌های Real-Time PCR و وسترن بلات اندازه‌گیری گردید. در نهایت، میزان فعالیت کاسپاز 3 و کاسپاز ۸ از طریق آزمون الایزا بررسی شد.یافته‌‌ها: نتایج نشان داد که زیست‌پذیری سلول‌های سرطانی تیمار شده با پپتید HL-7 با روشی وابسته به دوز و زمان، کاهش یافت (p<0.05). با افزایش غلظت پپتید HL-7 از 45 به 60 میکرومولار، به‌طور معناداری، بیان ژن‌های Fas، کاسپاز 8 و 3 در سطوح mRNA و پروتئین افزایش یافت (p<0.05). نتایج آزمون الایزا نشان داد که فعالیت کاسپاز 8 و کاسپاز ۳، به‌طور معناداری در سلول‌های سرطانی Hela تیمار شده با پپتید HL-7 نسبت به سلول‌های سرطانی بدون تیمار، افزایش نشان داد (p<0.05).نتیجه‌‌گیری: به‌نظر می‌رسد پپتید HL-7، از طریق تنظیم بیان ژن‌های درگیر در مسیر سیگنالینگ اپپتوز بیرونی، قادر به حذف سلول‌های سرطانی دهانه رحم است. در عین حال، مطالعات بیشتری در زمینه اهداف مولکولی جهت تأیید خاصیت ضدسرطانی پپتید HL-7 پیشنهاد می‌شود.
المصادر:
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Choi KE, Hwang CJ, Gu SM, Park MH, Kim JH, Park JH & et al. Cancer cell growth inhibitory effect of bee venom via increase of death receptor 3 expression and inactivation of NF-kappa B in NSCLC cells. 2014; 6(8): 2210-28.
de la Vega RC & Possani LD. Overview of scorpion toxins specific for Na+ channels and related peptides: biodiversity, structure–function relationships and evolution. 2005; 46(8): 831-44.
Dias NB, de Souza BM, Cocchi FK, Chalkidis HM, Dorce VA & Palma MS. Profiling the short, linear, non-disulfide bond-containing peptidome from the venom of the scorpion Tityus obscurus. Journal of proteomics. 2018; 170: 70-9.
Elmore S. Apoptosis: a review of programmed cell death. Toxicologic pathology. 2007; 35(4): 495-516.
Erdeş E, Doğan TS, Coşar İ, Danışman T, Kunt KB, Şeker T & et al. Characterization of Leiurus abdullahbayrami (Scorpiones: Buthidae) venom: peptide profile, cytotoxicity and antimicrobial activity. Journal of venomous animals and toxins including tropical diseases. 2014; 20: 1-8.
Guo X, Ma C, Du Q, Wei R, Wang L, Zhou M & et al. Two peptides, TsAP-1 and TsAP-2, from the venom of the Brazilian yellow scorpion, Tityus serrulatus: evaluation of their antimicrobial and anticancer activities. 2013; 95(9): 1784-94.
Han Z, Pantazis P, Wyche JH, Kouttab N, Kidd VJ & Hendrickson EA. A Fas-associated death domain protein-dependent mechanism mediates the apoptotic action of non-steroidal anti-inflammatory drugs in the human leukemic Jurkat cell line. Journal of Biological Chemistry. 2001; 276(42): 38748-54.
Hanahan D. Hallmarks of cancer: new dimensions. Cancer discovery. 2022; 12(1): 31-46.
Huang Y, He Q, Hillman MJ, Rong R & Sheikh MS. Sulindac sulfide-induced apoptosis involves death receptor 5 and the caspase 8-dependent pathway in human colon and prostate cancer cells. Cancer research. 2001; 61(18): 6918-24.
Ip SW, Chu YL, Yu CS, Chen PY, Ho HC, Yang JS & et al. Bee venom induces apoptosis through intracellular Ca2+‐modulated intrinsic death pathway in human bladder cancer cells. International Journal of Urology. 2012; 19(1): 61-70.
Jo M, Park MH, Kollipara PS, An BJ, Song HS, Han SB & et al. Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway. Toxicology and applied pharmacology. 2012; 258(1): 72-81.
Kong GM, Tao WH, Diao YL, Fang PH, Wang JJ, Bo P & et al. Melittin induces human gastric cancer cell apoptosis via activation of mitochondrial pathway. World journal of gastroenterology. 2016; 22(11): 3186.
Lourenço WR. The evolution and distribution of noxious species of scorpions (Arachnida: Scorpiones). Journal of venomous animals and toxins including tropical diseases. 2018; 24.
Nabi G, Ahmad N, Ullah S & Khan S. Therapeutic applications of scorpion venom in cancer: Mini review. Journal of Biology and Life Sciences. 2015; 6(1): 57.
Pfeffer CM & Singh AT. Apoptosis: a target for anticancer therapy. International journal of molecular sciences. 2018; 19(2): 448.
Santibáñez-López CE, Francke OF & Prendini L. Shining a light into the world’s deepest caves: phylogenetic systematics of the troglobiotic scorpion genus Alacran francke, 1982 (Typhlochactidae: Alacraninae). Invertebrate Systematics. 2014; 28(6): 643-64.
Setayesh-Mehr Z & Asoodeh A. Biochemical characterization of HL-7 and HL-10 peptides identified from scorpion venom of Hemiscorpius lepturus. International Journal of Peptide Research and Therapeutics. 2018; 24: 421-30.
Setayesh-Mehr Z, Asoodeh A & Poorsargol M. Upregulation of Bax, TNF-α and down-regulation of Bcl-2 in liver cancer cells treated with HL-7 and HL-10 peptides. 2021; 76(9): 2735-43.
Shin JM, Jeong YJ, Cho HJ, Park KK, Chung IK, Lee IK & et al. Melittin suppresses HIF-1α/VEGF expression through inhibition of ERK and mTOR/p70S6K pathway in human cervical carcinoma cells. PloS one. 2013; 8(7): e69380.
Tu WC, Wu CC, Hsieh HL, Chen CY & Hsu SL. Honeybee venom induces calcium-dependent but caspase-independent apoptotic cell death in human melanoma A2058 cells. Toxicon. 2008; 52(2): 318-329.
Zeng XC, Corzo G & Hahin R. Scorpion venom peptides without disulfide bridges. IUBMB life. 2005; 57(1): 13-21.
Zhang H, Zhao B, Huang C, Meng XM, Bian EB & Li J. Melittin restores PTEN expression by down-regulating HDAC2 in human hepatocelluar carcinoma HepG2 cells. PloS one. 2014; 9(5): e95520.
Zheng J, Lee HL, Ham YW, Song HS, Song MJ & Hong JT. Anti-cancer effect of bee venom on colon cancer cell growth by activation of death receptors and inhibition of nuclear factor kappa B. 2015; 6(42): 44437.
Zhu H, Hu B, Ling W, Su Y, Qiu S, Xiao W & et al. Adenovirus E1A reverses the resistance of normal primary human lung fibroblast cells to TRAIL through DR5 upregulation and caspase 8-dependent pathway. Cancer biology & therapy. 2006; 5(2): 180-8.
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Chippaux JP & Goyffon M. Epidemiology of scorpionism: a global appraisal. Acta tropica. 2008; 107(2): 71-9.
Choi KE, Hwang CJ, Gu SM, Park MH, Kim JH, Park JH & et al. Cancer cell growth inhibitory effect of bee venom via increase of death receptor 3 expression and inactivation of NF-kappa B in NSCLC cells. 2014; 6(8): 2210-28.
de la Vega RC & Possani LD. Overview of scorpion toxins specific for Na+ channels and related peptides: biodiversity, structure–function relationships and evolution. 2005; 46(8): 831-44.
Dias NB, de Souza BM, Cocchi FK, Chalkidis HM, Dorce VA & Palma MS. Profiling the short, linear, non-disulfide bond-containing peptidome from the venom of the scorpion Tityus obscurus. Journal of proteomics. 2018; 170: 70-9.
Elmore S. Apoptosis: a review of programmed cell death. Toxicologic pathology. 2007; 35(4): 495-516.
Erdeş E, Doğan TS, Coşar İ, Danışman T, Kunt KB, Şeker T & et al. Characterization of Leiurus abdullahbayrami (Scorpiones: Buthidae) venom: peptide profile, cytotoxicity and antimicrobial activity. Journal of venomous animals and toxins including tropical diseases. 2014; 20: 1-8.
Guo X, Ma C, Du Q, Wei R, Wang L, Zhou M & et al. Two peptides, TsAP-1 and TsAP-2, from the venom of the Brazilian yellow scorpion, Tityus serrulatus: evaluation of their antimicrobial and anticancer activities. 2013; 95(9): 1784-94.
Han Z, Pantazis P, Wyche JH, Kouttab N, Kidd VJ & Hendrickson EA. A Fas-associated death domain protein-dependent mechanism mediates the apoptotic action of non-steroidal anti-inflammatory drugs in the human leukemic Jurkat cell line. Journal of Biological Chemistry. 2001; 276(42): 38748-54.
Hanahan D. Hallmarks of cancer: new dimensions. Cancer discovery. 2022; 12(1): 31-46.
Huang Y, He Q, Hillman MJ, Rong R & Sheikh MS. Sulindac sulfide-induced apoptosis involves death receptor 5 and the caspase 8-dependent pathway in human colon and prostate cancer cells. Cancer research. 2001; 61(18): 6918-24.
Ip SW, Chu YL, Yu CS, Chen PY, Ho HC, Yang JS & et al. Bee venom induces apoptosis through intracellular Ca2+‐modulated intrinsic death pathway in human bladder cancer cells. International Journal of Urology. 2012; 19(1): 61-70.
Jo M, Park MH, Kollipara PS, An BJ, Song HS, Han SB & et al. Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway. Toxicology and applied pharmacology. 2012; 258(1): 72-81.
Kong GM, Tao WH, Diao YL, Fang PH, Wang JJ, Bo P & et al. Melittin induces human gastric cancer cell apoptosis via activation of mitochondrial pathway. World journal of gastroenterology. 2016; 22(11): 3186.
Lourenço WR. The evolution and distribution of noxious species of scorpions (Arachnida: Scorpiones). Journal of venomous animals and toxins including tropical diseases. 2018; 24.
Nabi G, Ahmad N, Ullah S & Khan S. Therapeutic applications of scorpion venom in cancer: Mini review. Journal of Biology and Life Sciences. 2015; 6(1): 57.
Pfeffer CM & Singh AT. Apoptosis: a target for anticancer therapy. International journal of molecular sciences. 2018; 19(2): 448.
Santibáñez-López CE, Francke OF & Prendini L. Shining a light into the world’s deepest caves: phylogenetic systematics of the troglobiotic scorpion genus Alacran francke, 1982 (Typhlochactidae: Alacraninae). Invertebrate Systematics. 2014; 28(6): 643-64.
Setayesh-Mehr Z & Asoodeh A. Biochemical characterization of HL-7 and HL-10 peptides identified from scorpion venom of Hemiscorpius lepturus. International Journal of Peptide Research and Therapeutics. 2018; 24: 421-30.
Setayesh-Mehr Z, Asoodeh A & Poorsargol M. Upregulation of Bax, TNF-α and down-regulation of Bcl-2 in liver cancer cells treated with HL-7 and HL-10 peptides. 2021; 76(9): 2735-43.
Shin JM, Jeong YJ, Cho HJ, Park KK, Chung IK, Lee IK & et al. Melittin suppresses HIF-1α/VEGF expression through inhibition of ERK and mTOR/p70S6K pathway in human cervical carcinoma cells. PloS one. 2013; 8(7): e69380.
Tu WC, Wu CC, Hsieh HL, Chen CY & Hsu SL. Honeybee venom induces calcium-dependent but caspase-independent apoptotic cell death in human melanoma A2058 cells. Toxicon. 2008; 52(2): 318-329.
Zeng XC, Corzo G & Hahin R. Scorpion venom peptides without disulfide bridges. IUBMB life. 2005; 57(1): 13-21.
Zhang H, Zhao B, Huang C, Meng XM, Bian EB & Li J. Melittin restores PTEN expression by down-regulating HDAC2 in human hepatocelluar carcinoma HepG2 cells. PloS one. 2014; 9(5): e95520.
Zheng J, Lee HL, Ham YW, Song HS, Song MJ & Hong JT. Anti-cancer effect of bee venom on colon cancer cell growth by activation of death receptors and inhibition of nuclear factor kappa B. 2015; 6(42): 44437.
Zhu H, Hu B, Ling W, Su Y, Qiu S, Xiao W & et al. Adenovirus E1A reverses the resistance of normal primary human lung fibroblast cells to TRAIL through DR5 upregulation and caspase 8-dependent pathway. Cancer biology & therapy. 2006; 5(2): 180-8.
