Isovalerylspiramycin I suppresses small cell lung cancer growth via ROS-mediated DNA damage and ER Stress
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ABSTRACT: Characterized by rapid progression, early metastasis, and poor prognosis, small cell lung cancer (SCLC) is a highly malignant tumor with limited treatment breakthroughs for nearly 30 years. Exploring alternative approaches is urgent. Tumor cells are more susceptible to ROS triggers for they have a fragile redox balance compared to normal cells. Isovalerylspiramycin I (ISP-I), purified from a novel macrolide antibiotic carrimycin, inducing accumulation of ROS in several tumor cells, has shown impressive anti-tumor potential. While the specific details and mechanisms of ISP-I's anti-SCLC effects remain unrevealed. We demonstrated that, ISP-I inhibited SCLC growth dose-dependently in vitro and in vivo, with good safety profiles for showing low toxicity to normal cells (MRC-5) and mice at therapeutic doses. Then, we utilized SCLC cell lines H1048 and DMS53 to uncover the anti-SCLC mechanisms of ISP-I. Primarily, ISP-I acted as an inducer of ROS, leading to H1048 and DMS53 cells DNA damage and endoplasmic reticulum (ER) stress through ROS accumulation, ultimately resulting in tumor cells G2/M cell cycle arrest and apoptosis. In conclusion, our study has proven that ISP-I may be a promising therapeutic approach for SCLC with good safety profiles.
ORGANISM(S): Homo sapiens
PROVIDER: GSE244376 | GEO | 2023/10/10
REPOSITORIES: GEO
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