Husref Rizvanovic

Quantum dots (QDs), including CdSe/ZnS, are nanoparticles emitting various wavelengths of fluorescent light depending on their size. Fluorescence allows them to be exploited for in vivo sensing/imaging of cancer cells. Nevertheless, thorough assessments of the effects of these commonly used QDs on cell stability are essentially required prior to their full applications. To investigate the effects of Cd QDs on the growth of human cervical cancer cells (HeLa), we utilized a growth assay, a reactive oxygen species (ROS) assay, an apoptosis assay, and RNA-seq. The growth assay results showed significant proliferation inhibition of HeLa cells by CdSe/ZnS. We revealed that smaller green CdSe/ZnS exerts more toxic effects than slightly larger yellow CdSe/ZnS. There were no significant increases of ROSs under the treatment of Cd QDs, which is consistent with the notion that low concentration of Cd QDs does not cause significant production of ROSs. In addition, we found that Cd QDs induced late apoptosis. RNA-Seq-based transcriptome analysis revealed that the exposure to green Cd QDs significantly upregulated antiapoptotic, antiproliferative, and antitumorigenic functions. The transcriptome profile also noted the downregulation of pro-proliferation, mitochondrial respiratory chain, detoxification, and receptor-mediated endocytosis. Taken together, our findings provide evidence that green CdSe/ZnS can be an alternative anticancer drug. In addition, our transcriptome analysis provides new insights into alteration of physiological state induced by CdSe/ZnS QDs in HeLa cancer cells.

Background: Although differentiated thyroid cancer has good prognosis, radioactive iodine (RAI) resistant thyroid cancer is difficult to treat. Current therapies for progressive RAI resistant thyroid cancer are not very effective. There is an unmet need for better therapeutic agents in this scenario. Studies have shown that aggressive thyroid cancers express matrix metalloproteinase −2 (MMP-2). Chlorotoxin is a selective MMP-2 agonist. Given that Saporin is a well-known ribosome-inactivating protein used for anti-cancer treatment, we hypothesized that Chlorotoxin-conjugated Saporin (CTX-SAP) would inhibit the growth of aggressive thyroid cancer cell lines expressing MMP-2.Methods: The ML-1 thyroid cancer cell line was used for this study because it is known to express MMP-2. ML-1 cells were treated with a toxin consisting of biotinylated Chlorotoxin bonded with a secondary conjugate of Streptavidin-ZAP containing Saporin (CTX-SAP) from 0 to 600 nM for 72 hours. Then, cell viability was measured via XTT assay at an absorbance of A_450-630. Control experiments were set up using Chlorotoxin and Saporin individually at the same varying concentrations.Results: After 7 hours of incubation, there was a statistically significant reduction in cell viability with increasing concentrations of the CTX-SAP conjugate (F=4.286, p=0.0057). In particular, the cell viability of ML-1 cells was decreased by 49.77% with the treatment of 600 nM of CTX-SAP (F=44.24), and the reduction in cell viability was statistically significant (Dunnett’s test pin vitrostudy demonstrated the efficacy of a CTX-SAP conjugate in reducing the viability of ML-1 thyroid cancer cells in a dose dependent manner. Further studies are needed to delineate the effectiveness of CTX-SAP in the treatment of aggressive thyroid cancer. Our study points towards MMP-2 as a potential target for RAI-resistant thyroid cancer.