Original Article

The The Effect of the Persian Gulf Jellyfish (Cassiopea andromeda) Venom on the Expression of P15, P21, P53, DNMT1, and Bcl-2 in Acute Lymphoblastic Leukemia Jurkat Cells

Abstract

Background: One of the acute hematologic malignancies is acute lymphoblastic leukemia (ALL), which is formed in B or T lymphocyte stem cells. Regarding the increasing tendency to herbal and marine studies, and on the other hand, the characteristics of Cassiopea andromeda Venom remain unclear, this study was performed to determine its effects on Jurkat cells as a model for T-ALL.

Materials and Methods: In this experimental study, the cells were treated with a variety of concentrations of Cassiopea andromeda venom at different periods and times. Growth inhibition and toxic effects of Cassiopea andromeda Venom were evaluated by methyl thiazole tetrazolium salt reduction (MTT test). The flow cytometry analysis was carried out using 7-aminoactinomycin D (7AAD) and Annexin V stains for evaluating this venom’s effect on apoptotic pathways. Besides, Real-Time PCR was performed to evaluate the relative gene expression.

Results: Cassiopea andromeda venom inhibited the growth of Jurkat cells in a concentration- and time manner. Jurkat cell growth was inhibited by 48.9%, after 72 hours of treatment with 250µg/mL Cassiopea andromeda venom. This venom increased the apoptotic process through the upregulation of p15INK4b and P53 proteins and downregulation of Bcl-2, p21 WAF1/CIP1, and DNMT1 in the Jurkat cell line.

Conclusion: Considering the growth inhibitory property of Cassiopea andromeda Venom, we recommend it as a part of combinational medication for treating ALL in animal trials and for other leukemias in vitro studies.

 

1. Shahverdi E, Shahriari M, Zare S, et al. Common Presenting Signs and Symptoms in Children with Acute Lymphoblastic Leukemia. Basic Clin Cancer Res. 2020;12(1):26-33.
2. Qian M, Cao X, Devidas M, et al. TP53 germline variations influence the predisposition and prognosis of B-cell acute lymphoblastic leukemia in children. J Clin Oncol. 2018;36(6):591-599.
3. De Braekeleer M, Douet-Guilbert N, De Braekeleer E. Prognostic impact of p15 gene aberrations in acute leukemia. Leuk Lymphoma. 2017;58(2):257-65.
4. Kreis N-N, Louwen F, Yuan J. The multifaceted p21 (Cip1/Waf1/CDKN1A) in cell differentiation, migration and cancer therapy. Cancers (Basel). 2019;11(9):1220.
5. Rahmani T, Azad M, Chahardouli B, et al. Patterns of DNMT1 promoter methylation in patients with acute lymphoblastic leukemia. Int J Hematol Oncol and Stem Cell Res. 2017;11(3):172-177.
6. Perini GF, Ribeiro GN, Neto JVP, et al. BCL-2 as therapeutic target for hematological malignancies. J Hematol Oncol. 2018;11(1):65.
7. Leone A, Lecci RM, Durante M, et al. Extract from the zooxanthellate jellyfish Cotylorhiza tuberculata modulates gap junction intercellular communication in human cell cultures. Mar Drugs. 2013;11(5):1728-62.
8. arian venoms. A review on health implications and possible therapeutic applications. Toxins (Basel). 2013;6(1):108-51.
9. Ovchinnikova TV, Balandin SV, Aleshina GM, et al. Aurelin, a novel antimicrobial peptide from jellyfish Aurelia aurita with structural features of defensins and channel-blocking toxins. Biochem Biophys Res Commun. 2006;348(2):514-23.
10. Ha SH, Jin F, Kwak CH, et al. Jellyfish extract induces apoptotic cell death through the p38 pathway and cell cycle arrest in chronic myelogenous leukemia K562 cells. PeerJ. 2017;5:e2895.
11. Begossi A, Salivonchyk S, Lopes PF, et al. Fishers’ knowledge on the coast of Brazil. J Ethnobiol Ethnomed. 2016;12(1):20
12. Nabipour I, Moradi M, Mohebbi G. A first record on population of the alien venomous jellyfish, Cassiopea andromeda (Forsskål, 1775)(Cnidaria: scyphozoa: Rhizostomea) in the Nayband Lagoon from Bushehr-Iran (Persian Gulf). J Chem Pharm Res. 2015;7(3):1710-3.
13. Mirshamsi MR, Omranipour R, Vazirizadeh A, et al. Persian Gulf Jellyfish (Cassiopea andromeda) venom fractions induce selective injury and cytochrome c release in mitochondria obtained from breast adenocarcinoma patients. Asian Pac J Cancer Prev. 2017;18(1):277-286.
14. Doonan LB, Lynham S, Quinlan C, et al. Venom composition does not vary greatly between different nematocyst types isolated from the primary tentacles of Olindias sambaquiensis (Cnidaria: Hydrozoa). Biol Bull. 2019;237(1):26-35.
15. Pereira RB, Evdokimov NM, Lefranc F, et al. Marine-derived anticancer agents: Clinical benefits, innovative mechanisms, and new targets. Mar Drugs. 2019;17(6):329.
16. Jimenez PC, Wilke DV, Costa-Lotufo LV. Marine drugs for cancer: Surfacing biotechnological innovations from the oceans. Clinics (Sao Paulo). 2018;73(suppl 1):e482s.
17. Wang T, He Q, Xiao L, et al. Mitochondrial dysfunction contributes to the cytotoxicity induced by tentacle extract from the jellyfish Cyanea capillata in rat renal tubular epithelial NRK-52E cells. Toxicon. 2013;74:1-7.
18. Callagy GM, Pharoah PD, Pinder SE, et al. Bcl-2 is a prognostic marker in breast cancer independently of the Nottingham Prognostic Index. Clin Cancer Res. 2006;12(8):2468-75.
19. Saikia S, Kolita B, Dutta PP, et al. Marine steroids as potential anticancer drug candidates: In silico investigation in search of inhibitors of Bcl-2 and CDK-4/Cyclin D1. Steroids. 2015;102:7-16.
20. McDonald ER, El-Deiry WS. Cell cycle control as a basis for cancer drug development. Int J Oncol. 2000;16(5):871-86.
21. Fridman JS, Lowe SW. Control of apoptosis by p53. Oncogene. 2003;22(56):9030-40.
22. Jha AK, Nikbakht M, Jain V, et al. p16INK4a and p15INK4b gene promoter methylation in cervical cancer patients. Oncol Lett. 2012;3(6):1331-5.
23. Matsuno N, Hoshino K, Nanri T, et al. p15 mRNA expression detected by real-time quantitative reverse transcriptase-polymerase chain reaction correlates with the methylation density of the gene in adult acute leukemia. Leuk Res. 2005;29(5):557-64.
24. El-Deiry WS. p21 (WAF1) mediates cell-cycle inhibition, relevant to cancer suppression and therapy. Cancer Res. 2016;76(18):5189-91.
25. Aubrey BJ, Kelly GL, Janic A, et al. How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression? Cell Death Differ. 2018;25(1):104-113.
26. Bodoor K, Haddad Y, Alkhateeb A, et al. DNA hypermethylation of cell cycle (p15 and p16) and apoptotic (p14, p53, DAPK and TMS1) genes in peripheral blood of leukemia patients. Asian Pac J Cancer Prev. 2014;15(1):75-84.
27. Christiansen DH, Andersen MK, Pedersen-Bjergaard J. Methylation of p15 INK4B is common, is associated with deletion of genes on chromosome arm 7q and predicts a poor prognosis in therapy-related myelodysplasia and acute myeloid leukemia. Leukemia. 2003;17(9):1813-9.
Files
IssueVol 17, No 3 (2023) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijhoscr.v17i3.13307
Keywords
Acute Lymphoblastic Leukemia, Apoptosis, Cnidaria

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Dehghani R, Amrooni A, Hosseinpour Soleimani F, Mohebbi G, Obeidi N. The The Effect of the Persian Gulf Jellyfish (Cassiopea andromeda) Venom on the Expression of P15, P21, P53, DNMT1, and Bcl-2 in Acute Lymphoblastic Leukemia Jurkat Cells. Int J Hematol Oncol Stem Cell Res. 2023;17(3):177-185.