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Antiproliferative and proapoptotic activities of Sea Cucumber H. Leucospilota extract on breast carcinoma cell line (SK-BR-3)

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Abstract

Background

Sea cucumber is a natural resource rich in many important pharmacological compounds. this study aimed to investigate the effect of H. leucospilota extract on the induction of cell death and and Proapoptotic Activities.

Methods and Results

H. leucospilota was collected, the methanolic extract was prepared and in vitro cytotoxicity of H. leucospilota extract in the range of 12.5, 25, 50, 100, and 200 μg/mL concentrations for 48 hours on SK-BR-3 and MCR5 cells was determined. Analysis of apoptosis and cell cycle stages were performed using flow cytometry. the expressions of several apoptotic-related proteins in SK-BR-3 cells were evaluated using Western blot analysis. ROS formation and caspase activity were determined. GC-MS (involving a multistep temperature gradient and trimethylsilyl derivatives) and phytochemical analysis were used for identification of bioactive compounds. Methanolic extract inhibited the proliferation of the SK-BR-3 cell line in a dose- and time-dependent manner. As it was observed, exposure of the H. leucospilota extract triggered the apoptosis of the SK-BR-3 cells, induced DNA fragmentation, and arrested the cells in G2/M phase. treatment of the methanolic extract induced the downregulation of antiapoptotic Bcl-2 protein as well as the upregulation of Bax, caspase-3, caspase-7 proteins in SK-BR-3 cells. Methanolic extract-elicited apoptosis was accompanied with the elevated level of ROS. The GC-MS and phytochemical analysis revealed 30 compounds and the extract contained alkaloids, flavonoids, steroids, terpenoids, phenols, and saponins.

Conclusions

The antiproliferative and proapoptotic activities of the tested extract suggested the pharmacologic potential of H. leucospilota. Correspondingly, further characterizations of the identified compounds are in progress.

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Authors and Affiliations

Authors

Contributions

Masoud mahdavinia and Mostafa Khaledi constructed the research question, Bahman Moradipoodeh, Rahim Moradi, Mostafa Khaledi, and Maryam Abedini Baghbadorani constructed the research method, collected the biological material. Mostafa Khaledi, Bahman Moradipoodeh analyzed the data, wrote and approved the final text. Masoud mahdavinia analyzed the data, wrote and approved the final text.

Corresponding author

Correspondence to Masoud Mahdavinia.

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Conflict of interest

The authors declare no conflict of interest. This project was supported by Ahvaz Jondishapur University of Medical Sciences(TRC-9903).

Ethical approval

Institutional Ethics Committee of Ahvaz Jondishapur University of Medical Sciences approved the experimental protocol (Ethics Approval Code: IR.AJUMS.REC.1399.094).

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Khaledi, M., Moradipoodeh, B., Moradi, R. et al. Antiproliferative and proapoptotic activities of Sea Cucumber H. Leucospilota extract on breast carcinoma cell line (SK-BR-3). Mol Biol Rep 49, 1191–1200 (2022). https://doi.org/10.1007/s11033-021-06947-0

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