In Vitro and In Vivo Anti-Cancer Activity of Lasiokaurin in a Triple-Negative Breast Cancer Model.

Due to its intricate heterogeneity, high invasiveness, and poor prognosis, triple-negative breast cancer (TNBC) stands out as the most formidable subtype of breast cancer. At present, chemotherapy remains the prevailing treatment modality for TNBC, primarily due to its lack of estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth receptor 2 (HER2). However, clinical chemotherapy for TNBC is marked by its limited efficacy and a pronounced incidence of adverse effects. Consequently, there is a pressing need for novel drugs to treat TNBC. Given the rich repository of diverse natural compounds in traditional Chinese medicine, identifying potential anti-TNBC agents is a viable strategy. This study investigated lasiokaurin (LAS), a natural diterpenoid abundantly present in Isodon plants, revealing its significant anti-TNBC activity both in vitro and in vivo. Notably, LAS treatment induced cell cycle arrest, apoptosis, and DNA damage in TNBC cells, while concurrently inhibiting cell metastasis. In addition, LAS effectively inhibited the activation of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway and signal transducer and activator of transcription 3 (STAT3), thus establishing its potential for multitarget therapy against TNBC. Furthermore, LAS demonstrated its ability to reduce tumor growth in a xenograft mouse model without exerting detrimental effects on the body weight or vital organs, confirming its safe applicability for TNBC treatment. Overall, this study shows that LAS is a potent candidate for treating TNBC.

Effects of melittin on laying performance and intestinal barrier function of quails.

To study the effects of melittin on egg-laying performance and intestinal barrier of quails, 240 quails (aged 70 d) were randomly divided into 4 groups with 6 replicates (10 quails per replicate). They were fed with basal diet (group B), basal diet + 0.08 g/kg melittin (group BA1), basal diet + 0.12 g/kg melittin (group BA2) and basal diet + 0.16 g/kg melittin (group BA3). The experiment lasted for 21 days. The eggs were collected every day. At the end of the experiment, duodenal, jejunal, and ileal tissues were collected, and the cecal contents were sampled. Intestinal antioxidant index, barrier function, and intestinal flora were analyzed. The results showed that the addition of melittin significantly increased the laying rate and average egg weight. Addition of melittin significantly increased the antioxidant function, mechanical barrier, immune barrier, and the villus height to crypt depth ratio of small intestine. Addition of melittin had no significant effect on the α and ß diversity of cecal flora, but significantly increased the abundance of Bacteroidales at family level and genus level. Bioinformatics analysis of cecal content showed significant increase in COG functional category of cytoskeleton, and significant decrease in RNA processing and modification in group BA2. KEGG functional analysis showed significant decrease in steroid biosynthesis, caffeine metabolism, and cytochrome P450 pathways in group BA2. In conclusion, addition of 0.12 g/kg melittin to feed improved the laying performance and the intestinal antioxidant capacity and barrier function of quails but had no significant effect on the composition and structure of cecal microbial community. This study provides experimental data and theoretical basis for the application of melittin as a new quail feed additive.