scholarly journals De-novo NAD+ synthesis regulates SIRT1-FOXO1 apoptotic pathway in response to NQO1 substrates in lung cancer cells

Oncotarget ◽  
2016 ◽  
Vol 7 (38) ◽  
pp. 62503-62519 ◽  
Author(s):  
Huiying Liu ◽  
Rong Xing ◽  
Xuefang Cheng ◽  
Qingran Li ◽  
Fang Liu ◽  
...  
2019 ◽  
Vol 2019 ◽  
pp. 1-21 ◽  
Author(s):  
Meng-Hsuan Cheng ◽  
Hung-Ling Huang ◽  
Yen-You Lin ◽  
Kuan-Hao Tsui ◽  
Pei-Chin Chen ◽  
...  

Lung cancer is the leading cause of cancer deaths in the world, with a five-year survival rate of less than 30%. Clinically effective chemotherapeutic treatments at the initial stage may eventually face the dilemma of no drug being effective due to drug resistance; therefore, finding new effective drugs for lung cancer treatment is a necessary and important issue. Compounds capable of further increasing the oxidative stress of cancer cells are considered to have anticancer potential because they possessed the ability to induce apoptosis. This study mainly investigated the effects of BA6 (heteronemin), the marine sponge sesterterpene, on lung cancer cell apoptosis, via modulation of mitochondrial reactive oxygen species (mtROS) and oxidative phosphorylation (OXPHOS). BA6 has cellular cytotoxic activities against a variety of cancer cell lines, but it has no effect on nontumor cells. The BA6-treated lung cancer cells show a significant increase in both cellular ROS and mtROS, which in turn caused the loss of mitochondrial membrane potential (MMP). The increase of oxidative stress in lung cancer cells treated with BA6 was accompanied by a decrease in the expression of antioxidant enzymes Cu/Zn SOD, MnSOD, and catalase. In addition, OXPHOS performed in the mitochondria and glycolysis in the cytoplasm were inhibited, which subsequently reduced downstream ATP production. Pretreatment with mitochondria-targeted antioxidant MitoTEMPO reduced BA6-induced apoptosis through the mitochondria-dependent apoptotic pathway, which was accompanied by increased cell viability, decreased mtROS, enhanced MMP, and suppressed expression of cleaved caspase-3 and caspase-9 proteins. In conclusion, the results of this study clarify the mechanism of BA6-induced apoptosis in lung cancer cells via the mitochondrial apoptotic pathway, suggesting that it is a potentially innovative alternative to the treatment of human lung cancer.


2009 ◽  
Vol 24 (1-2) ◽  
pp. 95-104 ◽  
Author(s):  
Zheng-Guang Li ◽  
Ying-Lan Zhao ◽  
Xiaohua Wu ◽  
Hao-Yu Ye ◽  
Aihua Peng ◽  
...  

2019 ◽  
Vol 20 (16) ◽  
pp. 4020 ◽  
Author(s):  
Keisuke Baba ◽  
Toshitsugu Fujita ◽  
Sadatomo Tasaka ◽  
Hodaka Fujii

A de novo single-nucleotide mutation in the EGFR gene can cause the development of lung cancer. EGFR tyrosine kinase inhibitors (EGFR-TKIs) are used for clinical treatment of such lung cancers, but acquired resistance often mitigates their efficacy. Accordingly, monitoring of de novo and acquired nucleotide mutations is essential for clinical treatment of lung cancers with EGFR-TKIs. Previously, we reported that oligoribonucleotide interference-PCR (ORNi-PCR) can accurately and cost-effectively detect single-nucleotide mutations. In this study, we applied ORNi-PCR to simultaneous detection of the de novo L858R and acquired T790M mutations in the EGFR gene in lung cancer cells. First, we established optimal experimental conditions for ORNi-PCR to simultaneously detect the two single-nucleotide mutations in genomic DNA from lung cancer cells. The conditions we established could also be used for ORNi-PCR using complementary DNA reverse-transcribed from extracted RNA. We found that ORNi-PCR could detect lung cancer cells possessing both single-nucleotide mutations among a large number of cells harboring wild-type sequences, even when the cancer cells constituted less than ~0.2% of all cells. Our findings demonstrate that ORNi-PCR can simultaneously detect multiple single-nucleotide mutations in a gene of interest and might therefore be useful for simultaneous detection of EGFR mutations in clinical examinations.


2020 ◽  
Vol 44 (21) ◽  
pp. 9064-9072
Author(s):  
Burak Ay ◽  
Onur Şahin ◽  
Burcu Saygıdeğer Demir ◽  
Yasemin Saygideger ◽  
José M. López-de-Luzuriaga ◽  
...  

Two novel nickel(ii) complexes [NiLI]·CH3CN (1·CH3CN) and [Ni(H2LII)(NCS)2]·0.5H2O (2·0.5H2O) were fabricated and in in vitro experiments they both showed the dose dependent cytotoxicity and killed A549 lung cancer cells via an apoptotic pathway.


APOPTOSIS ◽  
2015 ◽  
Vol 20 (11) ◽  
pp. 1518-1529 ◽  
Author(s):  
Ahmed Kamal ◽  
V. Lakshma Nayak ◽  
Chandrakant Bagul ◽  
M. V. P. S. Vishnuvardhan ◽  
Adla Mallareddy

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