High IF Citations

[Cited FineTest Antibody] Current Research on KRAS Mutation Lung Cancer Treatment

FineTest antibody contributes to the research on KRAS mutation lung cancer treatment. The western blot is designed to measure γ-H2AX in NCI-H358 cells.

Publication Details
Article Title: Upgrade of chrysomycin A as a novel topoisomerase II inhibitor to curb KRAS-mutant lung adenocarcinoma progression
Journal Title: Pharmacological Research
DOI: 10.1016/j.phrs.2022.106565
IF: 10.334
PMID: 36414124

Abstract:       A primary strategy employed in cancer therapy is the inhibition of topoisomerase II (Topo II), implicated in cell survival. However, side effects and adverse reactions restrict the utilization of Topo II inhibitors. Thus, investigations focus on the discovery of novel compounds that are capable of inhibiting the Topo II enzyme and feature safer toxicological profiles. Herein, we upgrade an old antibiotic chrysomycin A from Streptomyces sp. 891 as a compelling Topo II enzyme inhibitor. Our results show that chrysomycin A is a new chemical entity. Notably, chrysomycin A targets the DNA-unwinding enzyme Topo II with an efficient binding potency and a significant inhibition of intracellular enzyme levels. Intriguingly, chrysomycin A kills KRAS-mutant lung adenocarcinoma cells and is negligible cytotoxic to normal cells at the cellular level, thus indicating a capability of potential treatment. Furthermore, mechanism studies demonstrate that chrysomycin A inhibits the Topo II enzyme and stimulates the accumulation of reactive oxygen species, thereby inducing DNA damage-mediated cancer cell apoptosis. Importantly, chrysomycin A exhibits excellent control of cancer progression and excellent safety in tumor-bearing models. Our results provide a chemical scaffold for the synthesis of new types of Topo II inhibitors and reveal a novel target for chrysomycin A to meet its further application.

Keywords:    Lung Cancer, Chrysomycin A, DNA damage, Apoptosis, Topoisomerase II activity, Reactive oxygen species

Western Blot

FineTest Product Sample Detection Target
anti- γ-H2AX antibody (FNab10441)  NCI-H358 cells γ-H2AX

Validated Image

Lung Cancer

Figure Source:  Pharmacol Res. 2022 Nov 19;187:106565. doi: 10.1016/j.phrs.2022.106565.

Fig. 4. Induction of ROS accumulation and DNA damage: (D) Up-regulation of γ-H2AX expression levels triggered by chrysomycin A. Expression levels of γ-H2AX protein were detected by western blots after treatment with chrysomycin A (0, 0.5, 1, or 2 µM) for 24 h.