Date Pit Carbon Dots Induce Acidic Inhibition of Peroxidase and Disrupt DNA Repair in Antibacteria Resistance.

Carbon nanodots (C-dots) are emerging as a new type of promising agent in anticancer, imaging, and new energy. Reports as well as the previous research indicate that certain C-dots can enhance targeted cancer therapy. However, in-depth mechanisms for such anticancer effect remain unclear. In this work, treatment provided by the date pit-derived C-dots, exhibits significant DNA damage; Annexin V/7-AAD-mediated apoptosis, and G2/M cell cycle arrest in prostate cancer cells. The application of C-dots to the cell generally leads to acidulation of the cell medium, cooperated with membrane compact. The date pit-derived C-dots are observed inhibiting the horseradish peroxidase. Moreover, the C-dots disrupt likely through nucleotide excision DNA repair at low dose during DNA ligation step suggesting the antimicrobial effect and targeting Pim-1, EGFR, mTOR, and DNA damage pathways in cancer cells. For the first time the detailed and novel mechanisms underlying the C-dots, derived from the date-pit, as an efficient, low-cost, and green nanomaterial are reveled for cancer therapy and anti-infection.

Systematic analysis of NLMP suggests nuclear localization of RTK/MET kinases resemble cancer cell clearance.

BACKGROUND: Some membrane proteins can translocate into the nucleus, defined as nuclear localized membrane proteins (NLMPs), including receptor tyrosine kinases (RTKs). We previously showed that nuclear MET (nMET), a member of RTKs, mediates cancer stem-like cells self-renewal to promote cancer recurrence. However, it is unknown that nMET or mMET, which is the ancestor in the evolution of cancer cell survival and clearance. Here, we aim to study the NLMP functions in cell death, differentiation and survival. METHOD: We applied the systematic reanalysis of functional NLMP and clinical investigations of nMET from databases. In addition, we used soft agar assay, immunoblotting, flow cytometry, and immunofluorescence confocal microscopy for examinations of nMET functions including stem-like cell formation, cell signaling, cell cycle regulation, and co-localization with regulators of cell signaling. ShRNA, antibody of recognizing surface membrane MET based treatment were used to downregulate endogenous nMET to uncover its function. RESULTS: We predicted and demonstrated that nMET and nEGFR are most likely not ancestors. nMET overexpression induces both cell death and survival with drug resistance and stem cell-like characters. Moreover, the paradoxical function of nMET in both cell death and cell survival is explained by the fact that nMET induces stem cell-like cell growth, DNA damage repair, to evade the drug sensitization for survival of single cells while non-stem cell-like nMET expressing single cells may undergo clearance by cell death through cell cycle arrest induced by p21. CONCLUSION: Taken together, our data suggest a link between nuclear RTK and cancer cell evolutionary clearance via cell death, and drug resistance for survival through stemness selection. Targeting evolved nuclear RTKs in cancer stem cells would be a novel avenue for precision cancer therapy.

Dysregulation of YAP by ARF Stimulated with Tea-derived Carbon Nanodots.

YAP is a downstream nuclear transcription factor of Hippo pathway which plays an essential role in development, cell growth, organ size and homeostasis. It was previously identified that elevation of YAP in genomics of genetic engineered mouse (GEM) model of prostate cancer is associated with Pten/Trp53 inactivation and ARF elevation hypothesizing the essential crosstalk of AKT/mTOR/YAP with ARF in prostate cancer. However, the detailed function and trafficking of YAP in cancer cells remains unclear. Using GEM microarray model, we found ARF dysregulates Hippo and Wnt pathways. In particular, ARF knockdown reduced non-nuclear localization of YAP which led to an increase in F-actin. Mechanistically, ARF knockdown suppressed protein turnover of ß-catenin/YAP, and therefore enhanced the activity of AKT and phosphorylation of YAP. Moreover, we found tea-derived carbon dots can interact with ARF in nucleus that may further lead to the non-nuclear localization of YAP. Thus, we reported a novel crosstalk of ARF/ß-catenin dysregulated YAP in Hippo pathway and a new approach to stimulate ARF-mediated signaling to inhibit nuclear YAP using nanomaterials implicating an innovative avenue for treatment of cancer.