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Effect of aspirin on the TNF-α-mediated cell survival and death pathways in breast cancer

  • Banita Thakur ORCID logo , Lekha Saha ORCID logo , Divya Dahiya and Alka Bhatia ORCID logo EMAIL logo
Published/Copyright: November 10, 2022
Journal of Basic and Clinical Physiology and Pharmacology
From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 34 Issue 1

Abstract

Objectives

Aspirin is an anti-inflammatory drug commonly used as an analgesic and in cardiovascular disorders. However, many studies have highlighted its anti-cancer properties, especially in colorectal, lung, head and neck, and breast cancers. In this work, we tried to study the effect of aspirin on the TNF-α-mediated cell survival and death pathways in two cell lines representing two different subtypes of breast cancer. TNF-α-mediated stimulation of a cell can result in its proliferation via the NF-κB pathway or its death via either apoptosis or a programmed form of necrosis called necroptosis. The latter is believed to come into the picture only when apoptosis is inhibited.

Methods

In this work, we studied the effect of aspirin on the TNF-α-mediated cell survival pathway and observed a decrease in expression of the NF-κB pathway regulators, its nuclear translocation, and phosphorylation in a dose-dependent manner. The effect of aspirin on the TNF-α-mediated cell death showed significant cytotoxicity at the higher doses (5–20 mM) of aspirin in both the breast cancer cell lines. The effect of aspirin on necroptosis was investigated after stimulating the cells with TNF-α and inhibiting apoptosis using Z-VAD-FMK.

Results

Though no significant effect was noted in breast cancer cell lines, the above protocol successfully induced necroptosis in L929, i.e., a positive control cell line for necroptosis having an intact necroptosis machinery. Even when combined with the chemotherapeutic drugs, the above regime failed to induce any significant necroptosis in breast cancer cells but was found effective in L929.

Conclusions

Overall, the findings show that while aspirin has the potential to inhibit the TNF-α-mediated cell survival pathway, it does not help sensitize breast cancer cells to necroptotic cell death induction.

Highlights

  • – Treatment with aspirin resulted in significant cytotoxicity in both [ER+(T47D) and TNBC(MDA-MB-231)] cell lines used in our study, especially at higher doses.

  • – Interestingly, the lower doses were observed to cause more necrosis or a mixed pattern of cell death, whereas the highest concentration led to predominant apoptosis.

  • –Low-dose aspirin treatment caused significant inhibition of the TNF-α-mediated survival pathway by inhibiting the phosphorylation and nuclear translocation of the P65 subunit of NF-κB.

  • – Though low-dose aspirin caused downregulation of pro-apoptosis molecules to some extent, there was no significant change in the expression of necroptosis pathway molecules in the breast cancer cell lines.

  • – Also, the breast cancer cells showed resistance to induction of necroptosis using an aspirin-based protocol, although the same resulted in a significant increase in necroptosis in L929 cells.

  • – In future work, a low-dose aspirin-based induction protocol can be exploited to cause cell death by necroptosis in those cancers with well-developed necroptosis machinery.

Keywords: aspirin treatment; breast cancer cell lines; chemotherapeutic drugs; estrogen receptor; necroptosis; triple-negative
Corresponding author: Dr. Alka Bhatia, MD, Pathology, Professor, Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Sector-12, Chandigarh 160012, India, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: The local Institutional Review Board deemed the study exempt from review.

  6. Availability of data and materials: The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

  7. Consent for publication: All authors consent to the publication of this work.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/jbcpp-2022-0112).

Received: 2022-04-25
Accepted: 2022-10-17
Published Online: 2022-11-10

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/jbcpp-2022-0112
Keywords for this article
aspirin treatment; breast cancer cell lines; chemotherapeutic drugs; estrogen receptor; necroptosis; triple-negative

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Peyronie’s disease: where are we at?
  4. Reviews
  5. Catheter-associated urinary tract infection: an overview
  6. Liver and heart failure: an ultrasound relationship
  7. Original Articles
  8. The intracellular fluid compartment is smaller than commonly believed when measured by whole-body bioimpedance
  9. Prevalence and distribution of causes of infertility according to women’s age – a cross-sectional study in a tertiary healthcare hospital setup
  10. Supplementation of antihypertensive drug regimen with vitamin E ameliorates alterations of primary haemodynamic parameters and total antioxidant capacity in ovariectomised rats
  11. Analgesic effect of curcumin topical formulation in knee osteoarthritis patients: a clinical trial
  12. ProACT in the management of stress urinary incontinence after radical prostatectomy. What happens after 8 years of follow up? monocentric analysis in 42 patients
  13. The effect of metformin on the metabolism of human vascular smooth muscle cells in high glucose conditions
  14. Physiological response of endurance exercise as a growth hormone mediator in adolescent women’s
  15. Effect of Om chanting and Yoga Nidra on depression anxiety stress, sleep quality and autonomic functions of hypertensive subjects – a randomized controlled trial
  16. Effectiveness of electrical vestibular nerve stimulation as adjunctive therapy to improve the cognitive functions in patients with Parkinson’s disease
  17. Role of interleukin-22 in tuberculosis patients
  18. Effect of aspirin on the TNF-α-mediated cell survival and death pathways in breast cancer
  19. Resting heart rate variability as a diagnostic marker of cardiovascular dysautonomia in postural tachycardia syndrome
  20. Effects of intensity and training on cardiovascular responses to the Valsalva maneouvre
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