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Co-inhibition of Pol η and ATR sensitizes cisplatin-resistant non-small cell lung cancer cells to cisplatin by impeding DNA damage repair.
In this study, we showed that there was no difference in intracellular uptake of cisplatin or the removal of platinum-DNA adducts between a cisplatin-resistant NSCLC cell line (A549/DR) and a cisplatin-sensitive NSCLC cell line (A549). However, the capacity to repair DNA interstrand crosslinks (ICLs) and double-strand breaks (DSBs) was significantly enhanced in the A549/DR cell line compared to 3 cisplatin-sensitive cell lines. We found that the protein and mRNA expression levels of Pol η, a Y-family translesion synthesis (TLS) polymerase, were markedly increased upon cisplatin exposure in A549/DR cells compared with A549...
Source: Acta Pharmacologica Sinica - May 31, 2018 Category: Drugs & Pharmacology Authors: Li XQ, Ren J, Chen P, Chen YJ, Wu M, Wu Y, Chen K, Li J Tags: Acta Pharmacol Sin Source Type: research

Inhibition of DNA ‑PK activity sensitizes A549 cells to X‑ray irradiation by inducing the ATM‑dependent DNA damage response.
In conclusion, inhibition of DNA‑PK activity increased the radiosensitivity of A549 cells to X‑ray irradiation. NU7026 treatment activated the ATM‑dependent DNA damage response and induced p73 apoptosis pathway. DNA‑PK inhibitor may be an effective constituent of radiosensitization products. DNA damage repair pathway could be a potential target for radiosensitization. PMID: 29620203 [PubMed - as supplied by publisher]
Source: Molecular Medicine Reports - April 6, 2018 Category: Molecular Biology Tags: Mol Med Rep Source Type: research

cAMP signaling inhibits radiation-induced ATM phosphorylation leading to the augmentation of apoptosis in human lung cancer cells
Conclusions: cAMP signaling inhibits radiation-induced ATM activation by PKA-dependent activation of PP2A, and this signaling mechanism augments radiation-induced apoptosis by reducing ATM-dependent activation of NF-kappaB in lung cancer cells.
Source: Molecular Cancer - February 24, 2014 Category: Cancer & Oncology Authors: Eun-Ah ChoEui-Jun KimSahng-June KwakYong-Sung Juhnn Source Type: research