Antitumor Potential of Marine and Freshwater Lectins

Often, even the most effective antineoplastic drugs currently used in clinic do not efficiently allow complete healing due to the related toxicity. The reason for the toxicity lies in the lack of selectivity for cancer cells of the vast majority of anticancer agents. Thus, the need for new potent anticancer compounds characterized by a better toxicological profile is compelling. Lectins belong to a particular class of non-immunogenic glycoproteins and have the characteristics to selectively bind specific sugar sequences on the surface of cells. This property is exploited to exclusively bind cancer cells and exert antitumor activity through the induction of different forms of regulated cell death and the inhibition of cancer cell proliferation. Thanks to the extraordinary biodiversity, marine environments represent a unique source of active natural compounds with anticancer potential. Several marine and freshwater organisms, ranging from the simplest alga to the most complex vertebrate, are amazingly enriched in these proteins. Remarkably, all studies gathered in this review show the impressive anticancer effect of each studied marine lectin combined with irrelevant toxicity in vitro and in vivo and pave the way to design clinical trials to assess the real antineoplastic potential of these promising proteins. It provides a concise and precise description of the experimental results, their interpretation as well as the experimental conclusions that can be drawn

Synthesis and biological evaluation of new bis-indolinone derivatives endowed with cytotoxic activity

A series of new Knoevenagel adducts, bearing two indolinone systems, has been synthe-sized and evaluated on 60 human cancer cell lines according to protocols available at the National Cancer Institute (Bethesda, MD, USA). Some derivatives proved to be potent antiproliferative agents, showing GI50 values in the submicromolar range. Compound 5b emerged as the most active and was further studied in Jurkat cells in order to determine the effects on cell-cycle phases and the kind of cell death induced. Finally, oxidative stress and DNA damage induced by compound 5b were also analyzed

Exploiting the Lability of Metal Halide Perovskites for Doping Semiconductor Nanocomposites

Cesium lead halides have intrinsically unstable crystal lattices and easily transform within perovskite and nonperovskite structures. In this work, we explore the conversion of the perovskite CsPbBr3 into Cs4PbBr6 in the presence of PbS at 450 °C to produce doped nanocrystal-based composites with embedded Cs4PbBr6 nanoprecipitates. We show that PbBr2 is extracted from CsPbBr3 and diffuses into the PbS lattice with a consequent increase in the concentration of free charge carriers. This new doping strategy enables the adjustment of the density of charge carriers between 1019 and 1020 cm-3, and it may serve as a general strategy for doping other nanocrystal-based semiconductors.M.C. has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 665385. ICN2 acknowledges funding from Generalitat de Catalunya 2017 SGR 327. ICN2 is supported by the Severo Ochoa program from Spanish MINECO (Grant No. SEV-2017-0706) and is funded by the CERCA Programme/Generalitat de Catalunya. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 823717 – ESTEEM3. M.V.K. acknowledges the support by the European Research Council under the Horizon 2020 Framework Program (ERC Consolidator Grant SCALE-HALO Grant Agreement No. 819740) and by FET-OPEN project no. 862656 (DROP-IT)

Characterization of a clonal human colon adenocarcinoma line intrinsically resistant to doxorubicin.

Intrinsic low-level resistance to anti-cancer drugs is a major problem in the treatment of gastrointestinal malignancies. To address the problem presented by intrinsically resistant tumours, we have isolated two monoclonal lines from LoVo human colon adenocarcinoma cells: LoVo/C7, which is intrinsically resistant to doxorubicin (DOX); and LoVo/C5, which shows the same resistance index for DOX as the mixed parental cell population. For comparison, we have included in the study a LoVo-resistant line selected by continuous exposure to DOX and expressing a typical multidrug resistant (MDR) phenotype. In these cell lines we have studied the expression and/or activity of a number of proteins, including P-glycoprotein 170 (P-gp), multidrug resistance-associated protein (MRP), lung resistance-related protein (LRP), glutathione (GSH)-dependent enzymes and protein kinase C (PKC) isoforms, which have been implicated in anti-cancer drug resistance. Intracellular DOX distribution has been assessed by confocal microscopy. The results of the present study indicate that resistance in LoVo/C7 cells cannot be attributed to alterations in P-gp, LRP or GSH/GSH-dependent enzyme levels. Increased expression of MRP, accompanied by alterations in the subcellular distribution of DOX, has been observed in LoVo/C7 cells; changes in PKC isoform pattern have been detected in both intrinsically and pharmacologically resistant cells

Exploiting the lability of metal halide perovskites for doping semiconductor nanocomposites

Cesium lead halides have intrinsically unstable crystal lattices and easily transform within perovskite and nonperovskite structures. In this work, we explore the conversion of the perovskite CsPbBr into CsPbBr in the presence of PbS at 450 °C to produce doped nanocrystal-based composites with embedded CsPbBr nanoprecipitates. We show that PbBr is extracted from CsPbBr and diffuses into the PbS lattice with a consequent increase in the concentration of free charge carriers. This new doping strategy enables the adjustment of the density of charge carriers between 10 19 and 10 20 cm -3, and it may serve as a general strategy for doping other nanocrystal-based semiconductors

Plasma-activated medium as an innovative anticancer strategy: Insight into its cellular and molecular impact on in vitro leukemia cells

Cold atmospheric plasma (CAP) has received attention as a potential anticancer strategy. In this study, culture medium was exposed to a microsecond-pulsed dielectric barrier discharge jet to produce plasma-activated medium (PAM). On the T-lymphoblastic cell line, PAM induced apoptosis through the activation of the intrinsic pathway and inhibited the cell-cycle progression. The use of the scavengers N-acetylcysteine or O-phenantroline significantly decreased the PAM proapoptotic activity. The genetic impact of PAM on TK6 cells was assessed, resulting in an increased micronuclei frequency. PAM exhibited cytotoxic effects even on leukemia cells cultivated in hypoxia, which plays a critical role in promoting chemoresistance. PAM was also tested on normal lymphocytes, showing its partial selectivity. Taken together, these results contribute to understand the pharmacotoxicological profile of CAP

The relevance of the SH2 domain for c-Src functionality in triple-negative breast cancer cells

The role of Src family kinases (SFKs) in human tumors has been always associated with tyrosine kinase activity and much less attention has been given to the SH2 and SH3 adapter domains. Here, we studied the role of the c-Src-SH2 domain in triple-negative breast cancer (TNBC). To this end, SUM159PT and MDA-MB-231 human cell lines were employed as model systems. These cells conditionally expressed, under tetracycline control (Tet-On system), a c-Src variant with point-inactivating mutation of the SH2 adapter domain (R175L). The expression of this mutant reduced the self-renewal capability of the enriched population of breast cancer stem cells (BCSCs), demonstrating the importance of the SH2 adapter domain of c-Src in the mammary gland carcinogenesis. In addition, the analysis of anchorage-independent growth, proliferation, migration, and invasiveness, all processes associated with tumorigenesis, showed that the SH2 domain of c-Src plays a very relevant role in their regulation. Furthermore, the transfection of two different aptamers directed to SH2-c-Src in both SUM159PT and MDA-MB-231 cells induced inhibition of their proliferation, migration, and invasiveness, strengthening the hypothesis that this domain is highly involved in TNBC tumorigenesis. Therefore, the SH2 domain of c-Src could be a promising therapeutic target and combined treatments with inhibitors of c-Src kinase enzymatic activity may represent a new therapeutic strategy for patients with TNBC, whose prognosis is currently very negative