Azithromycin and Ceftriaxone Differentially Activate NLRP3 in LPS Primed Cancer Cells

Tezcan G., Alsaadi M., Hamza S., Garanina E. E., Martynova E. V., Ziganshina G. R., ...Daha Fazla

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, cilt.23, sa.16, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 23 Sayı: 16
  • Basım Tarihi: 2022
  • Doi Numarası: 10.3390/ijms23169484
  • Dergi Adı: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Anahtar Kelimeler: azithromycin, ceftriaxone, Nod-like receptor protein 3 (NLRP3), inflammasome, cancer, OXYGEN SPECIES FORMATION, INFLAMMASOME ACTIVATION, BETA-LACTAMS, DNA-SYNTHESIS, ANTIBIOTICS, EXPRESSION, GROWTH, ALPHA, MECHANISMS, RECEPTOR
  • Bursa Uludağ Üniversitesi Adresli: Evet

Özet

Background: Cancer patients are prescribed antibiotics, such as macrolides and lactamides, for infection treatment. However, the effect of these antibiotics on NLRP3 activation remains largely unknown. Method: Lung cancer (A549) and prostate cancer (PC3) cell lines were primed with lipopolysaccharide (LPS) to activate NLRP3 transcription. Cells were then treated with azithromycin (Az) or ceftriaxone (Cf). NLRP3 activation was analyzed by qPCR, Western blot, and ELISA. Cell growth and viability were assessed by real-time cell analysis and Annexin V expression. Levels of 41 cytokines were also analyzed using a multiplex assay. Results: LPS-Az activated transcription of NLRP3, Pro-CASP-1, and Pro-IL-1 beta in A549 cells, while failing to upregulate NLRP3 and Pro-IL-1 beta in PC3 cells. LPS-Az decreased the secretion of pro-inflammatory cytokines while it induced the pro-angiogenic factors in A549 and PC3 cells. In contrast, LPS-Cf suppressed the expression of NLRP3-associated genes, NLRP3 protein expression, the inflammatory cytokine secretion in A549 and PC3 cells. LPS-Az and LPS-Cf had a limited effect on cell growth and viability. Discussion: Our data suggest that Cf could suppress LPS induced NLRP3, which should be considered when selecting antibiotics for cancer treatment. In contrast, the effect of Az on LPS primed NLRP3 and the inflammatory cytokines production appears to depend on the cancer cell origin. Therefore, these data indicate that considerations are required when selecting Az for the treatment of cancer patients.