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sIL-24 peptide, a human interleukin-24 isoform, induces mitochondrial-mediated apoptosis in human cancer cells

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Abstract

Purpose

Interleukin-24 (IL-24) is a unique cytokine in the IL-10 family that reveals tumor-suppressive activity against a broad range of cancers. Alternative splicing of human IL-24 generates several isoforms with different pro-apoptotic activities. In the current study, we aimed to investigate the cytotoxic properties of a recombinant smallest isoform of IL-24 (sIL-24) and the underlying molecular mechanisms in PC-3, A549, U937, and Raji cancer cells as well as normal cell line MRC-5.

Methods

Following treatment of the cells with recombinant sIL-24 peptide and full-length IL-24 protein, cytotoxicity was determined by MTT assay. Apoptosis induction was evaluated using annexin-V/PI double staining flow cytometry and Hoechst 33342 staining. The expression of Bax, Bcl-2, cytochrome c, and caspase-3 was analyzed by Western blotting.

Results

MTT assay exhibited that sIL-24 dose and time dependently inhibited the proliferation of IL-24 receptor-positive PC-3, U937, and Raji cells more effectively than full-length IL-24. In contrast, sIL-24 had little cytotoxic effect on A549 cells lacking the IL-24 receptor, or on MRC-5 normal cells. Flow cytometric analysis and morphological observation revealed an efficient apoptosis induction in the receptor-positive cells. Furthermore, Western blot assay demonstrated that cell death induced by sIL-24 was associated with upregulation of the Bax/Bcl-2 ratio, cytochrome c release, and the expression of cleaved caspase-3, suggesting that sIL-24 induced apoptosis mainly through the mitochondrial pathway. Notably, among the tested cells, induction of apoptosis was more significant in PC-3 cells.

Conclusion

Our results suggest that the sIL-24 peptide is a promising candidate for potential treatment of human cancers.

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Authors and Affiliations

  1. Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran

    Samira Valiyari, Mana Oloomi, Azadeh Mohammadi Farsani & Saeid Bouzari

  2. Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran

    Mona Salami

  3. Department of Molecular Medicine, Pasteur Institute of Iran, Tehran, Iran

    Reza Mahdian

  4. National Cell Bank of Iran (NCBI), Pasteur Institute of Iran, Tehran, Iran

    Mohammad Ali Shokrgozar

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  1. Samira Valiyari
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  2. Mona Salami
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  4. Mohammad Ali Shokrgozar
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Correspondence to Saeid Bouzari.

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We would like to thank Pasteur Institute of Iran for financial support of this project.

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The authors declare that they have no conflicts of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Valiyari, S., Salami, M., Mahdian, R. et al. sIL-24 peptide, a human interleukin-24 isoform, induces mitochondrial-mediated apoptosis in human cancer cells. Cancer Chemother Pharmacol 80, 451–459 (2017). https://doi.org/10.1007/s00280-017-3370-1

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