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

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 canc...

Full description

Saved in:
Bibliographic Details
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
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22094974