Claudin-12: guardian of the tissue barrier or friend of tumor cells.

Tight junctions (TJs) are an important component of cellular connectivity. Claudin family proteins, as a constituent of TJs, determine their barrier properties, cell polarity and paracellular permeability. Claudin-12 is an atypical member of the claudin family, as it belongs to the group of non-classical claudins that lack a PDZ-binding domain. It has been shown that claudin-12 is involved in paracellular Ca2+ transients and it is present in normal and hyperplastic tissues in addition to neoplastic tissues. Dysregulation of claudin-12 expression has been reported in various cancers, suggesting that this protein may play an important role in cancer cell migration, invasion, and metastasis. Some studies have shown that claudin-12 gene functions as a tumor suppressor, but others have reported that overexpression of claudin-12 significantly increases the metastatic properties of various tumor cells. Investigating this dual role of claudin-12 is of utmost importance and should therefore be studied in detail. The aim of this review is to provide an overview of the information available to date on claudin-12, including its structure, expression in various tissues and substances that may affect it, with a final focus on its role in cancer.

Assessment of the biological activity of Marrubium friwaldskyanum Boiss. (Lamiaceae).

Present scientific evidences about the biological activity and potential medical application of extracts derived from Marrubium friwaldskyanum Boiss. are limited. Therefore, our study was undertaken to define several main characteristics in this regard - in vitro cytotoxicity and antitumor properties, antibacterial activity and immunomodulatory potential. Extracts were obtained from different aerial parts of Marrubium friwaldskyanum - stems, leaves and flowers. The in vitro cytotoxicity and antitumor activity of the samples were evaluated by tetrazolium salt reduction tests and Neutral red uptake assays using four human cell lines (a normal fibroblastic and three adenocarcinoma cell lines/A549, HeLa, HT-29/) and by experiments with HT-29 tumor spheroids. Antibacterial activity toward Gram-negative (Escherichia coli) and Gram-positive (Bacillus cereus) species was assessed based on estimation of minimal inhibitory and minimal bactericidal concentrations as well as longitudinal studies on bacterial viability. Ex vivo assays with normal leukocytes were performed to define potential immunomodulatory activity of the extracts. Our results demonstrated selective antitumor activity of the extracts directed against colon adenocarcinoma HT-29 cells and cervical adenocarcinoma HeLa cell line. Metabolic activity of A549 lung adenocarcinoma cells was affected only by the sample derived from flowers. M. friwaldskyanum leaf and flower extracts showed the highest activity, which included reduction of HT-29 tumor spheroid growth and viability. The studied samples exhibited antibacterial activity against both bacterial species tested. Treatment with M. friwaldskyanum extracts affected specific leukocyte populations (HLA+, CD19+, CD11b+, CD25+ cells). These results demonstrate for the first time complex biological effects of extracts derived from M. friwaldskyanum and their potential to serve as a source of valuable compounds for the pharmaceutical industry.