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

Overview

Journal Int J Hematol Oncol Stem Cell Res

Specialty Hematology

Date 2023 Oct 11

PMID 37817966

Authors

Reza Dehghani

Ali Amrooni

Fatemeh Hosseinpour-Soleimani

Gholamhossein Mohebbi

Narges Obeidi

Affiliations

Soon will be listed here.

Abstract

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 unclear characteristics of Cassiopea andromeda Venom, this study was performed to determine its effects on Jurkat cells as a model for T-ALL. 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 to evaluate the venom's effect on apoptotic pathways. Besides, Real-Time PCR was performed to evaluate the relative gene expression. 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. The venom increased the apoptotic process through the upregulation of p15INK4b and P53 proteins and downregulation of Bcl-2, p21 , and DNMT1 in the Jurkat cell line. 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.

References

Saikia S, Kolita B, Dutta P, Dutta D, Neipihoi , Nath S . 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. DOI: 10.1016/j.steroids.2015.06.012. View

Matsuno N, Hoshino K, Nanri T, Kawakita T, Suzushima H, Kawano F . 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. DOI: 10.1016/j.leukres.2004.11.003. View

Callagy G, Pharoah P, Pinder S, Hsu F, Nielsen T, Ragaz J . Bcl-2 is a prognostic marker in breast cancer independently of the Nottingham Prognostic Index. Clin Cancer Res. 2006; 12(8):2468-75. DOI: 10.1158/1078-0432.CCR-05-2719. View

Doonan L, Lynham S, Quinlan C, Ibiji S, Winter C, Padilla G . Venom Composition Does Not Vary Greatly Between Different Nematocyst Types Isolated from the Primary Tentacles of (Cnidaria: Hydrozoa). Biol Bull. 2019; 237(1):26-35. DOI: 10.1086/705113. View

Perini G, Ribeiro G, Pinto Neto J, Campos L, Hamerschlak N . BCL-2 as therapeutic target for hematological malignancies. J Hematol Oncol. 2018; 11(1):65. PMC: 5946445. DOI: 10.1186/s13045-018-0608-2. View

Rahmani T, Azad M, Chahardouli B, Nasiri H, Vatanmakanian M, Kaviani S . Patterns of DNMT1 Promoter Methylation in Patients with Acute Lymphoblastic Leukemia. Int J Hematol Oncol Stem Cell Res. 2017; 11(3):172-177. PMC: 5625466. View

Mirshamsi M, Omranipour R, Vazirizadeh A, Fakhri A, Zangeneh F, Mohebbi G . 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. PMC: 5563113. DOI: 10.22034/APJCP.2017.18.1.277. View

Mariottini G, Pane L . Cytotoxic and cytolytic cnidarian venoms. A review on health implications and possible therapeutic applications. Toxins (Basel). 2014; 6(1):108-51. PMC: 3920253. DOI: 10.3390/toxins6010108. View

El-Deiry W . p21(WAF1) Mediates Cell-Cycle Inhibition, Relevant to Cancer Suppression and Therapy. Cancer Res. 2016; 76(18):5189-91. PMC: 5028108. DOI: 10.1158/0008-5472.CAN-16-2055. View

10.

McDonald 3rd E, El-Deiry W . Cell cycle control as a basis for cancer drug development (Review). Int J Oncol. 2000; 16(5):871-86. View

11.

De Braekeleer M, Douet-Guilbert N, De Braekeleer E . Prognostic impact of p15 gene aberrations in acute leukemia. Leuk Lymphoma. 2016; 58(2):257-265. DOI: 10.1080/10428194.2016.1201574. View

12.

Wang T, He Q, Xiao L, Wang Q, Zhang B, Wang B . 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. DOI: 10.1016/j.toxicon.2013.07.020. View

13.

Aubrey B, Kelly G, Janic A, Herold M, Strasser A . How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression?. Cell Death Differ. 2017; 25(1):104-113. PMC: 5729529. DOI: 10.1038/cdd.2017.169. View

14.

Qian M, Cao X, Devidas M, Yang W, Cheng C, Dai Y . TP53 Germline Variations Influence the Predisposition and Prognosis of B-Cell Acute Lymphoblastic Leukemia in Children. J Clin Oncol. 2018; 36(6):591-599. PMC: 5815403. DOI: 10.1200/JCO.2017.75.5215. View

15.

Pereira R, Evdokimov N, Lefranc F, Valentao P, Kornienko A, Pereira D . Marine-Derived Anticancer Agents: Clinical Benefits, Innovative Mechanisms, and New Targets. Mar Drugs. 2019; 17(6). PMC: 6627313. DOI: 10.3390/md17060329. View

16.

Christiansen D, Andersen M, Pedersen-Bjergaard J . Methylation of p15INK4B 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. DOI: 10.1038/sj.leu.2403054. View

17.

Leone A, Lecci R, Durante M, Piraino S . Extract from the zooxanthellate jellyfish Cotylorhiza tuberculata modulates gap junction intercellular communication in human cell cultures. Mar Drugs. 2013; 11(5):1728-62. PMC: 3707171. DOI: 10.3390/md11051728. View

18.

Kreis N, Louwen F, Yuan J . The Multifaceted p21 (Cip1/Waf1/) in Cell Differentiation, Migration and Cancer Therapy. Cancers (Basel). 2019; 11(9). PMC: 6770903. DOI: 10.3390/cancers11091220. View

19.

Bodoor K, Haddad Y, Alkhateeb A, Al-Abbadi A, Dowairi M, Magableh A . 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. DOI: 10.7314/apjcp.2014.15.1.75. View

20.

Fridman J, Lowe S . Control of apoptosis by p53. Oncogene. 2003; 22(56):9030-40. DOI: 10.1038/sj.onc.1207116. View