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Cancer stem cells (CSCs) are known to mediate metastasis and recurrence and are therefore a promising therapeutic target. In this study, we found that dihydrotanshinone (DHTS) inhibits CSC formation. DHTS inhibited mammosphere formation in a dose-dependent manner and showed significant tumor growth inhibition in a xenograft model. This compound reduced the CD44high/CD24low- and aldehyde dehydrogenase- (ALDH-) expressing cell population and the self-renewal-related genes Nanog, SOX2, OCT4, C-Myc, and CD44. DHTS induced NOX5 activation by increasing calcium, and NOX5 activation induced reactive oxygen species (ROS) production. ROS production reduced the nuclear phosphorylation levels of Stat3 and secreted IL-6 levels in the mammospheres. DHTS deregulated the dynamic equilibrium from non-stem cancer cells to CSCs by dephosphorylating Stat3 and decreasing IL-6 secretion and inhibiting CSC formation. These novel findings showed that DHTS-induced ROS deregulated the Stat3/IL-6 pathway and induced CSC death. NOX5 activation by DHTS inhibits CSC formation through ROS/Stat3/IL-6 signaling, and DHTS may be a promising potential therapeutic agent against breast CSCs.

Triple-negative breast cancer (TNBC) cells overexpress the epidermal growth factor receptor (EGFR). Nuclear EGFR (nEGFR) drives resistance to anti-EGFR therapy and is correlated with poor survival in breast cancer. Inhibition of EGFR nuclear translocation may be a reasonable approach for the treatment of TNBC. The anti-malarial drugs chloroquine and primaquine have been shown to promote an anticancer effect. The aim of the present study was to investigate the effect and mechanism of chloroquine- and primaquine-induced apoptosis of breast cancer cells. We showed that primaquine, a malaria drug, inhibits the growth, migration, and colony formation of breast cancer cells in vitro, and inhibits tumor growth in vivo. Primaquine induces damage to early endosomes and inhibits the nuclear translocation of EGFR. Primaquine inhibits the interaction of Stat3 and nEGFR and reduces the transcript and protein levels of c-Myc. Moreover, primaquine and chloroquine induce the apoptosis of breast cancer cells through c-Myc/Bcl-2 downregulation, induce early endosome damage and reduce nEGFR levels, and induce apoptosis in breast cancer through nEGFR/Stat3-dependent c-Myc downregulation. Our study of primaquine and chloroquine provides a rationale for targeting EGFR signaling components in the treatment of breast cancer.

The presence of breast cancer stem cells (BCSCs) induces the aggressive progression and recurrence of breast cancer. These cells are drug resistant, have the capacity to self-renew and differentiate and are involved in recurrence and metastasis, suggesting that targeting BCSCs may improve treatment efficacy. In this report, methanol extracts of carrot root were purified by means of silica gel, Sephadex LH-20, and preparative high-performance liquid chromatography to isolate a compound targeting mammosphere formation. We isolated the compound 6-methoxymellein, which inhibits the proliferation and migration of breast cancer cells, reduces mammosphere growth, decreases the proportion of CD44+/CD24− cells in breast cancer cells and decreases the expression of stemness-associated proteins c-Myc, Sox-2 and Oct4. 6-Methoxymellein reduces the nuclear localization of nuclear factor-κB (NF-κB) subunit p65 and p50. Subsequently, 6-methoxymellein decreases the mRNA transcription and secretion of IL-6 and IL-8. Our data suggest that 6-methoxymellein may be an anticancer agent that inhibits BCSCs via NF-κB/IL-6 and IL-8 regulation.

Background This exploratory study applied Q methodology to identify the types of family caregivers of older adults in nursing homes during the COVID-19 pandemic based on their perceptions of the caregiving role and explore each type’s characteristics. Methods Q statements were derived from in-depth interviews and a review of prior research. Q sorting was conducted using 39 P samples on a nine-point scale to determine Q distributions according to the degree of subjective agreeableness for each statement. In-depth interviews were conducted to determine why the subjects rated statements on either extreme. Results Four types of family caregivers were identified as a result of an analysis using the PC QUANAL program: caregiving-positive type (type I), caregiving-ambivalent type (type II), nursing home dependent type (type III), and caregiving conflict burnout type (type IV). Conclusion The study results can help develop interventions and strategies based on perceptions of caregiving and their associated characteristics to provide psychological support to family members of older adult care home residents during the COVID-19 pandemic. Accordingly, the following measures are recommended: continuous follow-up research on specific measures facilitating communication between nursing home staff and family caregivers in the event of a pandemic; development of tools for measuring burnout risk among family caregivers and practical interventions for those at high risk; efforts to improve the image of older adult care homes and change the conventional perceptions of caregiving.

Breast cancer stem cells (BCSCs) are responsible for tumor chemoresistance and recurrence. Targeting CSCs using natural compounds is a novel approach for cancer therapy. A CSC-inhibiting compound was purified from citrus extracts using silica gel, gel filtration and high-pressure liquid chromatography. The purified compound was identified as tangeretin by using nuclear magnetic resonance (NMR). Tangeretin inhibited cell proliferation, CSC formation and tumor growth, and modestly induced apoptosis in CSCs. The frequency of a subpopulation with a CSC phenotype (CD44+/CD24−) was reduced by tangeretin. Tangeretin reduced the total level and phosphorylated nuclear level of signal transducer and activator of transcription 3 (Stat3). Our results in this study show that tangeretin inhibits the Stat3 signaling pathway and induces CSC death, indicating that tangeretin may be a potential natural compound that targets breast cancer cells and CSCs.

Cancer stem cells (CSCs) have unique properties, including self-renewal, differentiation, and chemoresistance. In this study, we found that p21-activated kinase (PAK1) inhibitor (Group I, PAK inhibitor, IPA-3) and inactivator (ivermectin) treatments inhibit cell proliferation and that tumor growth of PAK1-knockout cells in a mouse model is significantly reduced. IPA-3 and ivermectin inhibit CSC formation. PAK1 physically interacts with Janus Kinase 2 (JAK2), and JAK2 inhibitor (TG101209) treatment inhibits mammosphere formation and reduces the nuclear PAK1 protein level. PAK1 interacts with signal transducer and activator of transcription 3 (Stat3), and PAK1 and Stat3 colocalize in the nucleus. We show through electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), and reporter assays that the PAK1/Stat3 complex binds to the IL-6 promoter and regulates the transcription of the IL-6 gene. Inhibition of PAK1 and JAK2 in mammospheres reduces the nuclear pStat3 and extracellular IL-6 levels. PAK1 inactivation inhibits CSC formation by decreasing pStat3 and extracellular IL-6 levels. Our results reveal that JAK2/PAK1 dysregulation inhibits the Stat3 signaling pathway and CSC formation, the PAK1/Stat3 complex regulates IL-6 gene expression, PAK1/Stat3 signaling regulates CSC formation, and PAK1 may be an important target for treating breast cancer.

Cancer stem cells have certain characteristics, such as self-renewal, differentiation, and drug resistance, which are related to tumor progression, maintenance, recurrence, and metastasis. In our study, we targeted breast cancer stem cells (BCSCs) using a natural compound, coriolic acid, from Salicornia herbacea L. This compound was isolated by mammosphere formation inhibition bioassay-guided fractionation and identified by using NMR spectroscopy and electrospray ionization mass spectrometry. Coriolic acid inhibited the formation of mammospheres and induced BCSC apoptosis. It also decreased the subpopulation of CD44high/CD24low cells, a cancer stem cell (CSC) phenotype, and specific genes related to CSCs, such as Nanog,Oct4, and CD44. Coriolic acid decreased the transcriptional and translational levels of the c-Myc gene, which is a CSC survival factor. These results indicated that coriolic acid could be a novel compound to target BCSCs via regulation of c-Myc.

Autophagy and mitophagy are essential survival mechanisms that enable cancer cells to adapt to metabolic stress, particularly during nutrient deprivation. Therefore, targeting these pathways presents a promising therapeutic strategy. Thus, this study aimed to investigate the potential of isopimaric acid (IPA), a diterpenoid compound derived from Torreya nucifera, to disrupt autophagy-related processes in colon cancer cells. Notably, IPA treatment promoted the accumulation of autophagosomes, as indicated by increased LC3-II and p62 protein levels, suggesting an inhibition of autophagic flux rather than an enhancement of initiation. Further analysis revealed that IPA impaired lysosomal function and blocked autophagosome degradation. IPA also suppressed mitophagy by downregulating key regulators, including PINK1 and Parkin, resulting in mitochondrial dysfunction and the accumulation of reactive oxygen species (ROS). Particularly, IPA was non-toxic under nutrient-rich conditions but induced significant cell death under serum starvation conditions. To our knowledge, these findings are the first to show that IPA selectively induces apoptotic cell death in nutrient-deprived colon cancer cells by disrupting both late-stage autophagy and PINK1/Parkin-mediated mitophagy. Furthermore, this research establishes the development of innovative therapeutic strategies that specifically target metabolic stress and combination therapy. [Display omitted]

Breast cancer is a major health problem that affects lives worldwide. Breast cancer stem cells (BCSCs) are small subpopulations of cells with capacities for drug resistance, self-renewal, recurrence, metastasis, and differentiation. Herein, powder extracts of beetroot were subjected to silica gel, gel filtration, thin layer chromatography (TLC), and preparatory high-pressure liquid chromatography (HPLC) for isolation of one compound, based on activity-guided purification using tumorsphere formation assays. The purified compound was identified as betavulgarin, using nuclear magnetic resonance spectroscopy and electrospray ionization (ESI) mass spectrometry. Betavulgarin suppressed the proliferation, migration, colony formation, and mammosphere formation of breast cancer cells and reduced the size of the CD44+/CD24− subpopulation and the expression of the self-renewal-related genes, C-Myc, Nanog, and Oct4. This compound decreased the total level and phosphorylated nuclear level of signal transducer and activator of transcription 3 (Stat3) and reduced the mRNA and protein levels of sex determining region Y (SRY)-box 2 (SOX2), in mammospheres. These data suggest that betavulgarin inhibit the Stat3/Sox2 signaling pathway and induces BCSC death, indicating betavulgarin might be an anticancer agent against breast cancer cells and BCSCs.

This study reports the green synthesis of bioactive zinc oxide nanoparticles (MK-7 ZnO NPs) using Nostoc sp. strain MK-7 extract as a natural reducing and stabilizing agent. The formation of ZnO NPs was confirmed by UV–visible spectroscopy with a characteristic absorption peak at 312 nm. FTIR analysis revealed the involvement of bioactive functional groups (O–H, C = O, C–O, and Zn–O), indicating their role in nanoparticle reduction and stabilization. XRD analysis confirmed the crystalline nature of the nanoparticles with a prominent peak at 36.3°, and the average crystallite size was calculated to be 41.9 nm using the Debye–Scherrer equation. FESEM and TEM analyses demonstrated a well-defined hexagonal morphology, while EDS confirmed high zinc purity (82.3% by weight). Biological evaluations revealed that MK-7 ZnO NPs exhibited significantly enhanced bioactivity compared to the crude extract. The nanoparticles showed strong antioxidant activity, achieving 89.04% ABTS radical scavenging with an IC50 value of 35 ± 5 µg/mL and superior ferric- and cupric-reducing capacities. In elastase inhibition assays, MK-7 ZnO NPs demonstrated notable anti-wrinkle potential (50.5% inhibition at 100 µg/mL; IC50 = 55 ± 5 µg/mL). Importantly, the nanoparticles significantly reduced viability of MDA-MB-231 breast cancer cells by inducing apoptosis, as confirmed by Annexin V-FITC/PI staining and flow cytometry. Furthermore, MK-7 ZnO NPs suppressed nitric oxide production and downregulated IL-6 secretion and mRNA expression, demonstrating potent anti-inflammatory and anticancer effects. Overall, the findings highlight the successful biosynthesis of structurally stable, hexagonal MK-7 ZnO NPs with enhanced antioxidant, anti-inflammatory, anti-wrinkle, and anticancer activities. These results underscore the promising potential of MK-7 ZnO NPs as multifunctional therapeutic agents, warranting further in vivo investigations for clinical translation.