Intracellular levels of reactive oxygen species correlate with ABT-263 sensitivity in non-small-cell lung cancer cells

Cancer Science
Keiko OhginoKenzo Soejima

Abstract

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...Continue Reading

References

Aug 28, 1998·Science·G Evan, T Littlewood
Mar 26, 2003·Seminars in Cancer Biology·Leigh Coultas, Andreas Strasser
Nov 19, 2004·Nature·Scott W LoweGerard Evan
Oct 22, 2005·Nature Reviews. Cancer·Stephen W Fesik
Feb 27, 2007·Oncogene·J M Adams, S Cory
May 3, 2008·Cancer Research·Christin TseSteven W Elmore
Jun 4, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alex R ShoemakerSteven W Elmore
Oct 15, 2008·Molecular Cancer Therapeutics·Scott AcklerAlex R Shoemaker
Jan 12, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nguyen TanLisa D Belmont
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Dec 21, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Andrew W RobertsRod Humerickhouse
Apr 13, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Charles M RudinLeena Gandhi
Aug 27, 2013·Molecular Cancer Therapeutics·Christian Billard
Dec 21, 2013·Nature Reviews. Molecular Cell Biology·Peter E CzabotarJerry M Adams
Jan 7, 2015·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Mar 5, 2015·Proceedings of the National Academy of Sciences of the United States of America·Anthony C FaberJeffrey A Engelman
May 9, 2015·Cell Death and Differentiation·A R D Delbridge, A Strasser
May 26, 2015·Cancer Cell·Bingshe HanXingming Deng
Oct 31, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Xuefeng WangFang Guo
Apr 7, 2016·Journal of Cancer Prevention·Chul-Ho Jeong, Sang Hoon Joo
Jan 7, 2018·Antioxidants & Redox Signaling·Sebastian Öther-Gee PohlShazib Pervaiz
Feb 17, 2018·Biomarker Insights·Seema KumariRamaRao Malla
Sep 27, 2018·Cell Death & Disease·Qi ShenHaifa Shen
Nov 2, 2018·Journal of Experimental & Clinical Cancer Research : CR·Haotian YangXiaowen Liang

❮ Previous
Next ❯

Citations

Nov 17, 2020·GeroScience·Melod MehdipourIrina M Conboy

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
Assay
flow cytometry
PCR
protein assay
X‐ray
transfection
FACS
Flow

Software Mentioned

FlowJo
GraphPad
GraphPad Prism

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis