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Manuscript ID : SJOAPB-2305-1408 (R2) Visit : 232 Page: 85 - 102

Article Type: Original Research

Examining the anticancer properties of HL-7 peptide through changes in Fas, caspase 8 and caspase 3 gene expression

Subject Areas : biochemical

Zahra Setayesh-Mehr 1 (Assistant Professor, Department of Biology, Faculty of Science, Zabol University, Zabol, Iran)
Hosein Kamaladini 2 (Assistant Professor, Department of Biology, Faculty of Science, Zabol University, Zabol, Iran)
Mohammad Hajitabar 3 (Master's Degree, Department of Biology, Faculty of Science, Zabol University, Zabol, Iran)

Received: 2023-05-19 Accepted : 2023-07-28 Published : 2023-04-21

Keywords: Caspase 8, Apoptosis, Caspase 3, cancer, Fas gene expression, Hela, Cervix, Peptide, HL-7,

Abstract :

Objective: Cervical cancer is an important cause of female mortality worldwide. The results obtained so far indicate the involvement of bioactive peptides in cancer treatment. In this regard, the aim of the present study is to investigate the anticancer properties of HL-7 peptide through changes in Fas, caspase 8 and caspase 3 geneexpression.Materials and methods: In this study, the viability of cervical cancer cells treated with HL-7 peptide at two concentrations of 45 and 60 μM at two times of 12 and 24 hours was investigated using MTT assay. Also, the expression of Fas, caspase 8 and caspase 3 genes was measured at mRNA and protein levels, respectively, using Real-Time PCR and Western Blot methods. Finally, the activity level of caspase 3 and caspase 8 was checked through ELISA test.Findings: The results showed that the viability of cancer cells treated with HL-7 peptide decreased in a dose- and time-dependent manner (p<0.05). By increasing the concentration of HL-7 peptide from 45 to 60 μM, significantly, the expression of Fas, caspase 8 and 3 genes increased in mRNA and protein levels (p<0.05). The results of the ELISA test showed that the activity of caspase 8 and caspase 3 significantly increased in Hela cancer cells treated with HL-7 peptide compared to untreated cancer cells (p<0.05).Conclusion: It seems that HL-7 peptide is able to eliminate cervical cancer cells by regulating the expression of genes involved in the extrinsic apoptosis signaling pathway. At the same time, more studies on molecular targets are suggested to confirm the anticancer properties of HL-7 peptide.

References:


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_||_

  1. Chippaux JP & Goyffon M. Epidemiology of scorpionism: a global appraisal. Acta tropica. 2008; 107(2): 71-9.
    2.
  2. 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.
    3.
  3. 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.
    4.
  4. 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.
    5.
  5. Elmore S. Apoptosis: a review of programmed cell death. Toxicologic pathology. 2007; 35(4): 495-516.
    6.
  6. 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.
    7.
  7. 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.
    8.
  8. 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.
    9.
  9. Hanahan D. Hallmarks of cancer: new dimensions. Cancer discovery. 2022; 12(1): 31-46.
    10.
  10. 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.
    11.
  11. 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.
    12.
  12. 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.
    13.
  13. 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.
    14.
  14. Lourenço WR. The evolution and distribution of noxious species of scorpions (Arachnida: Scorpiones). Journal of venomous animals and toxins including tropical diseases. 2018; 24.
    15.
  15. 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.
    16.
  16. Pfeffer CM & Singh AT. Apoptosis: a target for anticancer therapy. International journal of molecular sciences. 2018; 19(2): 448.
    17.
  17. 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.
    18.
  18. 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.
    19.
  19. 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.
    20.
  20. 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.
    21.
  21. 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.
    22.
  22. Zeng XC, Corzo G & Hahin R. Scorpion venom peptides without disulfide bridges. IUBMB life. 2005; 57(1): 13-21.
    23.
  23. 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.
    24.
  24. 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.
    25.
  25. 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.
    26.

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