scholarly journals ABT-737, a BH3 Mimetic, Enhances the Therapeutic Effects of Ionizing Radiation in K-ras Mutant Non-Small Cell Lung Cancer Preclinical Model

2022 ◽  
Vol 63 (1) ◽  
pp. 16
Author(s):  
Jung Mo Lee ◽  
Hey Soo Kim ◽  
Arum Kim ◽  
Yoon Soo Chang ◽  
Jin Gu Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Ionizing Radiation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Preclinical Model ◽  
Therapeutic Effects ◽  
Small Cell Lung ◽  
Bh3 Mimetic

scholarly journals A Small Compound KJ-28d Enhances the Sensitivity of Non-Small Cell Lung Cancer to Radio- and Chemotherapy

2019 ◽  
Vol 20 (23) ◽  
pp. 6026
Author(s):  
Hwani Ryu ◽  
Hyo Jeong Kim ◽  
Jie-Young Song ◽  
Sang-Gu Hwang ◽  
Jae-Sung Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Damage ◽  
Ionizing Radiation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Therapeutic Agent ◽  
Apoptotic Cell ◽  
Combined Treatment ◽  
Small Cell ◽  
Small Cell Lung

We previously reported on a poly (ADP-ribose) polymerase (PARP) 1/2 inhibitor N-(3-(hydroxycarbamoyl)phenyl)carboxamide (designated KJ-28d), which increased the death of human ovarian cancer BRCA1-deficient SNU-251 cells. In the present study, we further investigated the antitumor activities of KJ-28d in BRCA-proficient non-small cell lung cancer (NSCLC) cells to expand the use of PARP inhibitors. KJ-28d significantly inhibited the growth of NSCLC cells in vitro and in vivo, and induced DNA damage and reactive oxygen species in A549 and H1299 cells. Combined treatment with KJ-28d and ionizing radiation led to increased DNA damage responses in A549 and H1299 cells compared to KJ-28d or ionizing radiation alone, resulting in apoptotic cell death. Moreover, the combination of KJ-28d plus a DNA-damaging therapeutic agent (carboplatin, cisplatin, paclitaxel, or doxorubicin) synergistically inhibited cell proliferation, compared to either drug alone. Taken together, the findings demonstrate the potential of KJ-28d as an effective anti-cancer therapeutic agent for BRCA-deficient and -proficient cancer cells. KJ-28d might have potential as an adjuvant when used in combination with radiotherapy or DNA-damaging agents, pending further investigations.

scholarly journals Therapeutic effects of the novel Leucyl-tRNA synthetase inhibitor BC-LI-0186 in non-small cell lung cancer

2019 ◽  
Vol 11 ◽  
pp. 175883591984679 ◽  
Author(s):  
Eun Young Kim ◽  
Jin Gu Lee ◽  
Jung Mo Lee ◽  
Arum Kim ◽  
Hee Chan Yoo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Antitumor Effect ◽  
Inhibitory Effect ◽  
Trna Synthetase ◽  
Small Cell ◽  
Therapeutic Effects ◽  
Small Cell Lung

Objective: Leucyl-tRNA synthetase (LRS) is an aminoacyl-tRNA synthetase catalyzing ligation of leucine to its cognate tRNA and is involved in the activation of mTORC1 by sensing cytoplasmic leucine. In this study, the usefulness of LRS as a therapeutic target of non-small cell lung cancer (NSCLC) and the anticancer effect of the LRS inhibitor, BC-LI-0186, was evaluated. Methods: LRS expression and the antitumor effect of BC-LI-0186 were evaluated by immunohistochemical staining, immunoblotting, and live cell imaging. The in vivo antitumor effect of BC-LI-0186 was evaluated using Lox-Stop-Lox (LSL) K-ras G12D mice. Results: LRS was frequently overexpressed in NSCLC tissues, and its expression was positively correlated with mTORC1 activity. The guanosine-5’-triphosphate (GTP) binding status of RagB was related to the expression of LRS and the S6K phosphorylation. siRNA against LRS inhibited leucine-mediated mTORC1 activation and cell growth. BC-LI-0186 selectively inhibited phosphorylation of S6K without affecting phosphorylation of AKT and leucine-mediated co-localization of Raptor and LAMP2 in the lysosome. BC-LI-0186 induced cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3 and increase of p62 expression, showing that it has the autophagy-inducing property. BC-LI-0186 has the cytotoxic effect at nanomolar concentration and its GI50 value was negatively correlated with the degree of LRS expression. BC-LI-0186 showed the antitumor effect, which was comparable with that of cisplatin, and mTORC1 inhibitory effect in a lung cancer model. Conclusions: BC-LI-0186 inhibits the noncanonical mTORC1-activating function of LRS. These results provide a new therapeutic strategy for NSCLC and warrant future clinical development by targeting LRS.

scholarly journals TRIAP1 knockdown sensitizes non‐small cell lung cancer to ionizing radiation by disrupting redox homeostasis

2020 ◽  
Vol 11 (4) ◽  
pp. 1015-1025
Author(s):  
Chun‐cheng Hao ◽  
Jia‐ning Luo ◽  
Cui‐yang Xu ◽  
Xin‐yu Zhao ◽  
Zhen‐bin Zhong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Ionizing Radiation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Redox Homeostasis ◽  
Small Cell ◽  
Small Cell Lung

E-cadherin as a predictive marker of brain metastasis in non-small-cell lung cancer, and its regulation by pioglitazone in a preclinical model

2012 ◽  
Vol 109 (2) ◽  
pp. 219-227 ◽  
Author(s):  
Jin Young Yoo ◽  
Seung-Ho Yang ◽  
Jung Eun Lee ◽  
Deog Gon Cho ◽  
Hoon Kyo Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Predictive Marker ◽  
Small Cell ◽  
Preclinical Model ◽  
Small Cell Lung ◽  
E Cadherin

scholarly journals Iodide sensitizes genetically modified non-small cell lung cancer cells to ionizing radiation

2005 ◽  
Vol 13 (1) ◽  
pp. 74-81 ◽  
Author(s):  
L Zhang ◽  
S Sharma ◽  
J M Hershman ◽  
G A Brent ◽  
S M Dubinett ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Ionizing Radiation ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Genetically Modified ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung
Sign in / Sign up

Export Citation Format

Share Document