Chaetocin induces endoplasmic reticulum stress response and leads to death receptor 5-dependent apoptosis in human non-small cell lung cancer cells
Abstract Epigenetic abnormalities are associated with non-small cell lung cancer (NSCLC) initiation and progression. Epigenetic drugs are being studied and in clinical trials. However, the molecular mechanism underlying the apoptosis by the epigenetic agents remains unclear. SUV39H1 is an important methyl-transferase for lysine 9 on histone H3 and usually related to gene transcriptional suppression, and chaetocin acts as the inhibitor of SUV39H1. We demonstrated here that chaetocin effectively suppressed the growth of multiple lung cancer cells through inducing apoptosis in a death receptor 5 (DR5)-dependent manner. Chaetocin treatment activated endoplasmic reticulum (ER) stress which gave rise to the up-regulation of ATF3 and CHOP. Furthermore, ATF3 and CHOP contributed to the induction of DR5 and subsequent apoptosis. When SUV39H1 was silenced with siRNA, the expression of ATF3, CHOP and DR5 was elevated. Thereafter, knockdown of SUV39H1 induced apoptosis in NSCLC cells. In summary, chaetocin pharmacologically inhibits the activity of SUV39H1 which provokes ER stress and results in up-regulation of ATF3 and CHOP, leading to DR5-dependent apoptosis eventually. These findings provide a novel interpretation on the anti-neoplastic activity of epigenetic drugs as a new therapeutic approach in NSCLC.
Publication date: Available online 31 May 2020Source: Materials Science and Engineering: CAuthor(s): Vineela Parvathaneni, Nishant S. Kulkarni, Gautam Chauhan, Snehal K. Shukla, Rasha Elbatanony, BrijeshKumar Patel, Nitesh K. Kunda, Aaron Muth, Vivek Gupta
Propofol suppresses the progression of non‑small cell lung cancer via downregulation of the miR‑21‑5p/MAPK10 axis. Oncol Rep. 2020 May 21;: Authors: Wu X, Li X, Xu G Abstract Non‑small cell lung cancer (NSCLC) accounts for>80% of lung cancer cases and is the leading cause of cancer‑associated mortality worldwide. Propofol is an anesthetic drug frequently used during tumor resection. It is also known to exert inhibitory effects on cancer. Although the role of propofol in NSCLC has been reported, its underlying mechanisms remain unknown. The present study aimed therefore to investigate the m...
Effect of AGER on the biological behavior of non‑small cell lung cancer H1299 cells. Mol Med Rep. 2020 May 22;: Authors: Wang Q, Zhu W, Xiao G, Ding M, Chang J, Liao H Abstract Advanced glycosylation end-product specific receptor (AGER) is a multi-ligand cell surface receptor abnormally expressed in lung cancer, and is a member of the immunoglobulin superfamily. Therefore, this study aimed to explore the effect of AGER on the biological behavior of non‑small cell lung cancer (NSCLC) H1299 cell line. A microarray‑based gene expression profiling analysis of the GSE27262 dataset from the Gene Expres...
Publication date: Available online 29 May 2020Source: The Lancet Respiratory MedicineAuthor(s): Yi-Long Wu, Ying Cheng, Jianying Zhou, Shun Lu, Yiping Zhang, Jun Zhao, Dong-Wan Kim, Ross Andrew Soo, Sang-We Kim, Hongming Pan, Yuh-Min Chen, Chih-Feng Chian, Xiaoqing Liu, Daniel Shao Weng Tan, Rolf Bruns, Josef Straub, Andreas Johne, Jürgen Scheele, Keunchil Park, James Chih-Hsin Yang
Publication date: Available online 29 May 2020Source: The Lancet Respiratory MedicineAuthor(s): Rafael Rosell, Imane Chaib, Mariacarmela Santarpia
Overall survival (OS) benefit derived from frontline treatment with nivolumab plus ipilimumab combined with 2 cycles of platinum-doublet chemotherapy in patients with metastatic or recurrent non-small cell lung cancer was further improved after at least 12 months of follow-up.
kam Mistletoe (Viscum album) extracts have been used as alternative and complementary therapeutic preparations in multiple cancers for decades. Mistletoe lectins (ML-I, ML-II, and ML-III) are considered to be the main anticancer components of such preparations. In the present study, ML-II was transiently expressed in Nicotiana benthamiana using the pEAQ-HT expression system. Expression levels of up to 60 mg/kg of the infiltrated plant tissue were obtained, and a three-fold increase was achieved by adding the endoplasmic reticulum (ER) retention signal KDEL to the native ML-II sequence. The native protein containing His...
Conclusions: a combined clinical–radiomics model was not superior to a single clinical or single radiomics model to predict positive LNs. A radiomics model was able to separate high-risk and low-risk patients for OS; CTs reconstructed with Iterative Reconstructions (IR) algorithm showed the best model performance.
We report a case of successful desensitization therapy after osimertinib-induced urticaria. An 85-year-old Japanese woman received osimertinib as third-line therapy for NSCLC with the EGFR T790M mutation. After two days, she developed urticaria of the lower extremities. We started osimertinib desensitization therapy at 0.1 mg/day, which was gradually increased to 40 mg/day. She continued osimertinib for>12 months without adverse effects. Desensitization therapy with osimertinib could be useful for patients experiencing osimertinib-induced urticaria. PMID: 32461525 [PubMed - as supplied by publisher]
The FDA approved ramucirumab injection in combination with erlotinib for the first-line treatment of patients with metastatic non-small cell lung cancer with EGFR exon 19 deletions or exon 21 mutations.