Photodynamic and antiangiogenic activities of parietin liposomes in triple negative breast cancer.

Parietin (PTN) is an anthraquinone with promising efficacy in the inhibition of cancer cell proliferation and tumor growth. Due to its hydrophobicity, PTN is sparingly soluble under physiological conditions and has a low bioavailability. Hence, we presented PTN in liposomes to overcome these drawbacks. The prepared liposomes were characterized and their stability was also assessed in serum. Singlet oxygen quantum yield of PTN loaded liposomes was indirectly quantified using uric acid. The intracellular uptake of liposomes was studied by CLSM which indicated the perinuclear localization of PTN liposomes. Cellular viability assay and live/dead staining demonstrated both light and dose-dependent phototoxicity of PTN on the human breast cancer cell line. The mechanism of cellular uptake was investigated using different pathway inhibitors and the results showed that clathrin-mediated endocytosis is predominant. The colocalization experiment indicated that PTN is localized in both mitochondria and lysosomes. These findings together with flow cytometry analysis elucidated that apoptosis is the main mechanism underlying cell death post-PDT. Finally, the antiangiogenic effect of PTN liposomes was further evaluated in the chorioallantoic membrane (CAM) model and the results indicated that PDT induced vascular response was confined to the irradiated area leaving the non-irradiated unscathed.

The Role of Long Non-Coding RNAs (lncRNAs) in Female Oriented Cancers.

Recent advances in molecular biology have discovered the mysterious role of long non-coding RNAs (lncRNAs) as potential biomarkers for cancer diagnosis and targets for advanced cancer therapy. Studies have shown that lncRNAs take part in the incidence and development of cancers in humans. However, previously they were considered as mere RNA noise or transcription byproducts lacking any biological function. In this article, we present a summary of the progress on ascertaining the biological functions of five lncRNAs (HOTAIR, NEAT1, H19, MALAT1, and MEG3) in female-oriented cancers, including breast and gynecological cancers, with the perspective of carcinogenesis, cancer proliferation, and metastasis. We provide the current state of knowledge from the past five years of the literature to discuss the clinical importance of such lncRNAs as therapeutic targets or early diagnostic biomarkers. We reviewed the consequences, either oncogenic or tumor-suppressing features, of their aberrant expression in female-oriented cancers. We tried to explain the established mechanism by which they regulate cancer proliferation and metastasis by competing with miRNAs and other mechanisms involved via regulating genes and signaling pathways. In addition, we revealed the association between stated lncRNAs and chemo-resistance or radio-resistance and their potential clinical applications and future perspectives.

Surface-Tailored Zein Nanoparticles: Strategies and Applications.

Plant-derived proteins have emerged as leading candidates in several drug and food delivery applications in diverse pharmaceutical designs. Zein is considered one of the primary plant proteins obtained from maize, and is well known for its biocompatibility and safety in biomedical fields. The ability of zein to carry various pharmaceutically active substances (PAS) position it as a valuable contender for several in vitro and in vivo applications. The unique structure and possibility of surface covering with distinct coating shells or even surface chemical modifications have enabled zein utilization in active targeted and site-specific drug delivery. This work summarizes up-to-date studies on zein formulation technology based on its structural features. Additionally, the multiple applications of zein, including drug delivery, cellular imaging, and tissue engineering, are discussed with a focus on zein-based active targeted delivery systems and antigenic response to its potential in vivo applicability.

Surface tailored zein as a novel delivery system for hypericin: Application in photodynamic therapy.

Zein is an FDA-approved maize protein featured by its manipulative surface and the possibility of fabrication into nanomaterials. Although extensive research has been carried out in zein-based technology, limited work is available for the application of zein in the field of cancer photodynamic therapy (PDT). In this work, we report zein as a carrier for the natural photosensitizer hypericin in the PDT of hepatocellular carcinoma in vitro. Zein was modified through chemical PEGylation to form PEGylated zein micelles that were compared with two zein nanoparticle formulations physically stabilized by either the lecithin/pluronic mixture or sodium caseinate. FT-IR, 1HNMR and HP-SEC MALS approaches were employed to confirm the chemical PEGylation of zein. Our developed zein nanoparticles and micelles were further characterized by photon correlation spectroscopy (PCS) and atomic force microscopy (AFM). The obtained results showed relatively smaller sizes and higher encapsulation of hypericin in the micellar zein than the nanoparticle-based formulations. Phototoxicity on hepatocellular carcinoma (HepG2 cells) manifested a dose-dependent toxicity pattern of all designed zein formulations. However, superior cytotoxicity was prominent for the hypericin-based micelles, which was influenced by the higher cellular uptake profile. Consequently, the treated HepG2 cells manifested a higher level of intracellular generated ROS and disruption of mitochondrial membrane potential, which induced apoptotic cell death. Comparatively, the designed hypericin formulations indicated lower phototoxicity profile in murine fibroblast L929 cells reflecting their safety on normal cells. Our investigations suggested that the surface-modified zein could be employed to enhance the delivery of the hydrophobic hypericin in PDT and pave the way for future in vivo and clinical applications in cancer treatment.

Potent Cytotoxicity of Four Cameroonian Plant Extracts on Different Cancer Cell Lines.

In this study, the potential cytotoxicity of four plant extracts originated from Cameroon: Xylopia aethiopica (XA), Imperata cylindrica (IC), Echinops giganteus (EG) and Dorstenia psilurus (DP) were examined in vitro. We tested the anti-proliferative activity of the methanolic extracts of these compounds using MTT assay on seven different human cancer cell lines: HeLa, MDA-MB-231, A549, HepG2, U-87, SK-OV-3 and HL60. Induction of cell death was assessed by cell cycle analysis, apoptosis was determined by Annexin V-FITC binding and caspase 3/7 activity. As well, changes in mitochondrial membrane potential (MMP) and cell migration were tested. The genetic toxicity, using the alkaline comet assay, was evaluated. The studied extracts inhibited the cell proliferation of all tested cancer cell lines with concentration dependent effect over time. All of these extracts mainly induced apoptosis of HeLa cells by the accumulation of hypodiploid cells in the sub-G0/G1 phase and increasing the activity of caspase 3/7, as well they showed potential MMP disturbance and expressed a marked inhibitory effect on cell migration. Assessment of probable genetic toxicity by these extracts revealed no or minimum incidence of genetic toxicity. Therefore, the studied plant extracts are exhibiting potent anticancer activity based upon marked induction of tumor-cell death.