Interleukin-32θ Triggers Cellular Senescence and Reduces Sensitivity to Doxorubicin-Mediated Cytotoxicity in MDA-MB-231 Cells

• Published in: International journal of molecular sciences 2021-05, Vol.22 (9), p.4974
• Main Authors: Pham, Thu-Huyen, Park, Hyo-Min, Kim, Jinju, Hong, Jin-Tae, Yoon, Do-Young
• Format: Article
• Language: English
• Subjects: Apoptosis; Autophagy; Breast cancer; Cancer therapies; Cell cycle; Cell division; Cell growth; Cell proliferation; Chemotherapy; Cyclin-dependent kinases; Cytokines; Cytology; Cytotoxicity; DNA damage; Doxorubicin; Drug dosages; Drug resistance; G1 phase; Gene expression; Genomic instability; Genotoxicity; Kinases; Metastases; Metastasis; Morphology; Nucleoli; Protein expression; Proteins; Senescence; Tumor microenvironment; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22094974

The recently discovered interleukin (IL)- 32 isoform IL-32θ exerts anti-metastatic effects in the breast tumor microenvironment. However, the involvement of IL-32θ in breast cancer cell proliferation is not yet fully understood; therefore, the current study aimed to determine how IL-32θ affects cancer cell growth and evaluated the responses of IL-32θ-expressing cells to other cancer therapy. We compared the functions of IL-32θ in triple-negative breast cancer MDA-MB-231 cells that stably express IL-32θ, with MDA-MB-231 cells transfected with a mock vector. Slower growth was observed in cells expressing IL-32θ than in control cells, and changes were noted in nuclear morphology, mitotic division, and nucleolar size between the two groups of cells. Interleukin-32θ significantly reduced the colony-forming ability of MDA-MB-231 cells and induced permanent cell cycle arrest at the G1 phase. Long-term IL-32θ accumulation triggered permanent senescence and chromosomal instability in MDA-MB-231 cells. Genotoxic drug doxorubicin (DR) reduced the viability of MDA-MB-231 cells not expressing IL-32θ more than in cells expressing IL-32θ. Overall, these findings suggest that IL-32θ exerts antiproliferative effects in breast cancer cells and initiates senescence, which may cause DR resistance. Therefore, targeting IL-32θ in combination with DR treatment may not be suitable for treating metastatic breast cancer.