Low response rate and recurrence are common issues in lung cancer; thus, identifying a potential compound for these patients is essential. Utilizing an in silico screening method, we identified withaferin A (WA), a cell-permeable steroidal lactone initially extracted from Withania somnifera, as a potential anti–lung cancer and anti–lung cancer stem-like cell (CSC) agent. First, we demonstrated that WA exhibited potent cytotoxicity in several lung cancer cells, as evidenced by low IC50 values. WA concurrently induced autophagy and apoptosis and the activation of reactive oxygen species (ROS), which plays an upstream role in mediating WA-elicited effects. The increase in p62 indicated that WA may modulate the autophagy flux followed by apoptosis. In vivo research also demonstrated the anti-tumor effect of WA treatment. We subsequently demonstrated that WA could inhibit the growth of lung CSCs, decrease side population cells, and inhibit lung cancer spheroid-forming capacity, at least through downregulation of mTOR/STAT3 signaling. Furthermore, the combination of WA and chemotherapeutic drugs, including cisplatin and pemetrexed, exerted synergistic effects on the inhibition of epidermal growth factor receptor (EGFR) wild-type lung cancer cell viability. In addition, WA can further enhance the cytotoxic effect of cisplatin in lung CSCs. Therefore, WA alone or in combination with standard chemotherapy is a potential treatment option for EGFR wild-type lung cancer and may decrease the occurrence of cisplatin resistance by inhibiting lung CSCs.

Gram-stain-negative, aerobic and rod-shaped bacterial strains, designated SSM26T and SSM44, were isolated from a sea surface microlayer sample from the Ross Sea, Antarctica. Analysis of the 16S rRNA gene sequences of strains SSM26T and SSM44 revealed a clear affiliation with the genus Pseudomonas . Based on the results of phylogenetic analysis, strains SSM26T and SSM44 showed the closest phylogenetic relationship with the species Pseudomonas sabulinigri KCTC 22137T with the 16S rRNA gene sequence similarity level of 98.5 %. Strains SSM26T and SSM44 grew optimally at 30 °C, pH 7.0–7.5 and 0.5–10.0 % NaCl (w/v). The major cellular fatty acids were C18 : 1  ω7c (31.3–34.9 %), C16 : 0 (15.5–20.2 %), summed feature 3 (C16 : 1  ω7c/C16 : 1  ω6c; 19.5–25.4 %) and C12 : 0 (6.0–9.3 %). The genomic DNA G+C content of each strain was 56.2 mol%. Genomic relatedness analyses based on the average nucleotide identity and the genome-to-genome distance showed that strains SSM26T and SSM44 constituted a single species that was clearly distinguishable from its phylogenetically close relatives. The combined phenotypic, chemotaxonomic, genomic and phylogenetic data also showed that strains SSM26T and SSM44 could be distinguished from validly published members of the genus Pseudomonas . Thus, these strains should be classified as representing a novel species in the genus Pseudomonas , for which the name Pseudomonas neustonica sp. nov. is proposed with the type strain SSM26T (=KCCM 43193T=JCM 31284T=PAMC 28426T) and a sister strain SSM44 (=KCCM 43194=JCM 31285=PAMC 28427).

Declines in physiological functions are the predominant risk factors for age-related diseases, such as cancers and neurodegenerative diseases. Therefore, delaying the aging process is believed to be beneficial in preventing the onset of age-related diseases. Previous studies have demonstrated that Graptopetalum paraguayense (GP) extract inhibits liver cancer cell growth and reduces the pathological phenotypes of Alzheimer’s disease (AD) in patient IPS-derived neurons. Here, we show that GP extract suppresses β-amyloid pathology in SH-SYS5Y-APP695 cells and APP/PS1 mice. Moreover, AMP-activated protein kinase (AMPK) activity is enhanced by GP extract in U87 cells and APP/PS1 mice. Intriguingly, GP extract enhances autophagy in SH-SYS5Y-APP695 cells, U87 cells, and the nematode Caenorhabditis elegans, suggesting a conserved molecular mechanism by which GP extract might regulate autophagy. In agreement with its role as an autophagy activator, GP extract markedly diminishes mobility decline in polyglutamine Q35 mutants and aged wild-type N2 animals in C. elegans. Furthermore, GP extract significantly extends lifespan in C. elegans.

Background Colorectal cancer (CRC) is a highly prevalent cancer type with limited targeted therapies available and 5-year survival rate, particularly for late-stage patients. There have been numerous attempts to repurpose drugs to tackle this problem. It has been reported that autophagy inducers could augment the effect of certain chemotherapeutic agents by enhancing immunogenic cell death (ICD). Methods In this study, we employed bioinformatics tools to identify thioridazine (THD), an antipsychotic drug, and found that it could induce autophagy and ICD in CRC. Then in vitro and in vivo experiments were performed to further elucidate the molecular mechanism of THD in CRC. Results THD was found to induce endoplasmic reticulum (ER) stress in CRC cells by activating the eIF2α/ATF4/CHOP axis and facilitating the accumulation of secretory autophagosomes, leading to ICD. In addition, THD showed a remarkable ICD-activating effect when combined with oxaliplatin (OXA) to prevent tumor progression in the mouse model. Conclusions Together, our findings suggest that the repurposed function of THD in inhibiting CRC involves the upregulation of autophagosomes and ER stress signals, promoting the release of ICD markers, and providing a potential candidate to enhance the clinical outcome for CRC treatment.