Intracellular levels of reactive oxygen species correlate with ABT-263 sensitivity in non-small-cell lung cancer cells.
Keiko OhginoHideki TeraiHiroyuki YasudaShigenari NukagaJunko HamamotoTetsuo TaniAoi KurodaDaisuke AraiKota IshiokaKeita MasuzawaShinnosuke IkemuraIchiro KawadaKatsuhiko NaokiKoichi FukunagaKenzo SoejimaPublished in: Cancer science (2020)
ABT-263 (Navitoclax) is a BH3-mimetic drugs targeting anti-apoptotic B-cell lymphoma-2 (BCL-2) family proteins, including BCL-2, BCL-xL, and BCL-w, thereby inducing apoptosis. In small-cell lung cancer (SCLC) cells, the response to ABT-263 is associated with the expression of myeloid cell leukemia-1 (MCL-1) protein, however the efficacy of ABT-263 in non-small-cell lung cancer (NSCLC) has not been thoroughly evaluated. There are currently no established biomarkers for predicting the efficacy of ABT-263 treatment in NSCLC. We screened a panel of different NSCLC cell lines and found that ABT-263 inhibited cell proliferation and induced apoptosis in Calu-1, Calu-3, and BID007 cells. Inconsistent with previous reports on SCLC, low levels of MCL-1 did not predict the response to ABT-263 in NSCLC cells, however we found that intracellular levels of reactive oxygen species (ROS) in cancer cells were associated with sensitivity to ABT-263 in NSCLC cells. We also showed that increasing the level of intracellular ROS could enhance the sensitivity to ABT-263 in NSCLC cells. In summary, we propose that the intracellular levels of ROS could be used as a potential novel biomarker for predicting a response to ABT-263 in NSCLC. Furthermore, we show some evidence supporting the further assessment of ABT-263 as a new therapeutic strategy in patients with NSCLC combined with agents regulating ROS levels. We believe that our findings and follow-up studies on this matter would lead to novel diagnostic and treatment strategies in patients with NSCLC.
Keyphrases
- induced apoptosis
- small cell lung cancer
- reactive oxygen species
- endoplasmic reticulum stress
- cell cycle arrest
- cell death
- advanced non small cell lung cancer
- oxidative stress
- signaling pathway
- brain metastases
- cell proliferation
- pi k akt
- dna damage
- poor prognosis
- bone marrow
- single cell
- long non coding rna
- immune response
- climate change
- small molecule
- risk assessment
- anti inflammatory
- smoking cessation
- drug induced