Abstract 372: Optimizing vertical MAPK pathway inhibition for RAS mutant non-small cell lung cancer

Author(s):  
Jens Köhler ◽  
Cloud P. Paweletz ◽  
Yanan Kuang ◽  
Prafulla Gokhale ◽  
Margaret K. Wilkens ◽  
...  
2020 ◽  
Vol 18 ◽  
pp. 205873922094233
Author(s):  
Xiaoying Bai ◽  
Wei Wang ◽  
Yan Wang ◽  
Jing Li

Lung cancer in humans is majorly represented by non-small cell lung cancer cells, and there is a constant search for an efficient therapeutic approach. This study aims to find the anti-proliferative and apoptotic effects of matricin on H1299 cells via activation of MAPK pathway. Non-small cell H1299 cells were subjected to viability analysis with MTT assay and anti-proliferation analysis with different concentrations of matricin. Apoptosis was determined with annexin V/propidium iodide (PI) and flow cytometric analysis. Analysis of oxidative stress markers, reduced glutathione, lipid peroxidation (LPO), superoxide dismutase (SOD), and catalase (CAT) activities were done using standard assay kits. Apoptosis enzymes caspase-3, caspase-8, and caspase-9 levels were measured using colorimetric kit analysis. Western blot analysis on apoptotic proteins was performed to determine the involvement of MAPK pathway activation in apoptosis. Matricin significantly ( P < 0.01) exerted anti-proliferative activities on H1299 cells in a dose-dependent manner. Flow cytometric apoptosis analysis showed increasing concentrations of matricin had increased apoptosis ( P < 0.01) in the H1299 cells. Levels of oxidative stress markers were altered significantly ( P < 0.01) by matricin. Caspase-3, caspase-8, and caspase-9 levels were significantly increased ( P < 0.01) in matricin-treated H1299 cells. Western blot analysis showed decreased expression of anti-apoptotic Bcl-2, increased expressions of Bax and phosphorylated JNK, ERK 1/2, and p-38 MAPK proteins in matricin-treated H1299 cells. Matricin has significant anti-proliferative and apoptosis-inducing effects via activation of MAPK pathway in non-small cell lung cancer cells.


Respirology ◽  
2009 ◽  
Vol 14 (6) ◽  
pp. 850-858 ◽  
Author(s):  
Yongseon CHO ◽  
Mee-Ja PARK ◽  
Mira PARK ◽  
Sun Seek MIN ◽  
Jaeyong YEE ◽  
...  

2018 ◽  
Vol 38 (1) ◽  
pp. 18 ◽  
Author(s):  
Hailu Fu ◽  
Huijun Gao ◽  
Xiaoyu Qi ◽  
Lei Zhao ◽  
Donghua Wu ◽  
...  

2018 ◽  
Vol 7 (11) ◽  
pp. 5505-5513 ◽  
Author(s):  
Paul Lesueur ◽  
Alexandre Escande ◽  
Juliette Thariat ◽  
Enora Vauléon ◽  
Isabelle Monnet ◽  
...  

2019 ◽  
Vol 20 (14) ◽  
pp. 3415 ◽  
Author(s):  
Kun Wang ◽  
Bonan Chen ◽  
Ting Yin ◽  
Yujuan Zhan ◽  
Yuhua Lu ◽  
...  

The main mechanistic function of most chemotherapeutic drugs is mediated by inducing mitochondria-dependent apoptosis. Tumor cells usually respond to upregulate autophagy to eliminate impaired mitochondria for survival. Hypothetically, inhibiting autophagy might promote mitochondria-dependent apoptosis, thus enhancing the efficacy of chemotherapeutic therapies. We previously identified N-methylparoxetine (NMP) as an inducer of mitochondrial fragmentation with subsequent apoptosis in non-small cell lung cancer (NSCLC) cells. We discovered that ROS was accumulated in NMP-treated NSCLC cells, followed by c-Jun N-terminal kinase (JNK) and p38 MAP kinase (p38) activation. This was reversed by the application of a reactive oxygen species (ROS) scavenger, N-acetylcysteine (NAC), leading to a reduction in apoptosis. Our data suggested that NMP induced apoptosis in NSCLC cells by activating mitogen-activated protein kinase (MAPK) pathway. We further speculated that the remarkable increase of ROS in NMP-treated NSCLC cells might result from an inhibition of autophagy. Our current data confirmed that NMP blocked autophagy flux at late stage wherein lysosomal acidification was inhibited. Taken together, this study demonstrated that NMP could exert dual apoptotic functions—mitochondria impairment and, concomitantly, autophagy inhibition. NMP-related excessive ROS accumulation induced apoptosis by activating the MAPK pathway in NSCLC cells.


2021 ◽  
Author(s):  
Maoshu Zhu ◽  
Hui Zhang ◽  
Fuhua Lu ◽  
Zhaowei Wang ◽  
Yulong Wu ◽  
...  

Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer. Ubiquitination is closely related to the development of lung cancer. However, the biological importance of newly discovered ubiquitin specific peptidase 52 (USP52) in NSCLC remained unclear. Here, our findings identify USP52 as a novel tumor suppressor of NSCLC, the low expression of USP52 predicts a poor prognosis for NSCLC patients. This study demonstrates that USP52 inhibits cancer cell proliferation through downregulation of cyclin D1 as well as AKT/mTOR signaling pathway inhibition. Meanwhile, USP25 also suppresses NSCLC progression via enhancing PTEN stability in cancer cells, which further indicates the significance/importance of USP52 in NSCLC suppression.


2020 ◽  
Author(s):  
Zhiwei Zhou ◽  
Chiara Ambrogio ◽  
Asim Bera ◽  
Li Qing ◽  
Xu Cheng-Xiong ◽  
...  

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