Incense-burning smoke ingredient Auramine enhances lincRNA-p21 expression for chemosensitization in p53-mutated non-small cell lung cancer

J Hazard Mater. 2024 Sep 15:477:135105. doi: 10.1016/j.jhazmat.2024.135105. Epub 2024 Jul 10.

Abstract

Incense-burning smoke is a deleterious air pollutant that initiates cytotoxic effects by inducing apoptosis in lung epithelial cells and also acts as a risk factor for lung cancers. Auramine, an ingredient of incense smoke, has been implicated in tumor progression and cellular sensitivity in non-small cell lung cancer (NSCLC) towards anti-cancer agents through unclear mechanisms. Tumor protein p53 (TP53)-activated long intergenic non-coding RNA-p21 (lincRNA-p21) undertakes a pivotal role in regulating cell apoptosis and chemosensitivity. TP53 mutations prevalent in 50% of NSCLC, contribute to diminished therapeutic efficacy. However, the influence of auramine on chemotherapy-induced lincRNA-p21 expression and apoptosis in NSCLC with different TP53 genetic statuses remains unexplored. This study disclosed that both wild-type p53 (wtp53) and mutant p53 (mutp53) mediate lincRNA-p21 expression, albeit through distinct promoter enhancers, p53-response element (p53RE) and non-B DNA structure G-quadruplex (GQ), respectively. Intriguingly, auramine functions as an effective stabilizer of the GQ structure, augmenting mutp53-mediated lincRNA-p21 expression and enhancing apoptosis and cellular sensitivity to chemotherapy in mutp53-expressing NSCLC cells. These findings suggest a mechanism by which mutp53, in the presence of auramine, is endowed with tumor-suppressing function akin to wtp53, thereby aiding in combating chemoresistance in NSCLC cells harboring TP53 mutations.

Keywords: Chemoresistance; GQ structure; Incense-burning smoke; Long non-coding RNA; TP53.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Apoptosis / drug effects
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / drug effects
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Mutation* / drug effects
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Smoke / adverse effects
  • Tumor Suppressor Protein p53* / genetics
  • Tumor Suppressor Protein p53* / metabolism

Substances

  • Tumor Suppressor Protein p53
  • RNA, Long Noncoding
  • Antineoplastic Agents
  • Smoke
  • TP53 protein, human