sIL-24 peptide, a human interleukin-24 isoform, induces mitochondrial-mediated apoptosis in human cancer cells.
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.
['Valiyari|Samira|S|', 'Salami|Mona|M|', 'Mahdian|Reza|R|', 'Shokrgozar|Mohammad Ali|MA|', 'Oloomi|Mana|M|', 'Mohammadi Farsani|Azadeh|A|', 'Bouzari|Saeid|S|']
D017209:Apoptosis D045744:Cell Line, Tumor D006801:Humans D007378:Interleukins D009369:Neoplasms D020033:Protein Isoforms
sIL-24 peptide Apoptosis Cytotoxicity Anticancer