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We have previously reported that prodigiosin (2-methyl-3pentyl-6-methoxyprodigiosene) induces apoptosis in human hematopoietic cancer cell lines with no marked toxicity in nonmalignant cell lines. In this study, we demonstrate that prodigiosin induces apoptosis of B-cell chronic lymphocytic leukemia (B-CLL) cells (n=32 patients). The dose-response for the cytotoxic effect of prodigiosin was analyzed in cells from 12 patients showing an IC[sub 50] of 116 ± 25 nM. Prodigiosin induced apoptosis of B-CLL cells through caspase activation. We also analyzed the cytotoxic effect of prodigiosin in T cells from BCLL samples and no differences were observed with respect to leukemia cells. This is the first report showing that prodigiosin induces apoptosis in human primary cancer cells. [ABSTRACT FROM AUTHOR]

Prodigiosin (PG) is a red pigment produced by Serratia marcescens with pro-apoptotic activity in haematopoietic and gastrointestinal cancer cell lines, but no marked toxicity in non-malignant cells. Breast cancer is the most frequent malignancy among women in the European Union and better therapies are needed, especially for metastatic tumors. Moreover, multidrug resistance is a common phenomenon that appears during chemotherapy, necessitating more aggressive treatment as prognosis worsens. In this work, we extend our experiments on PG-induced apoptosis to breast cancer cells. PG was potently cytotoxic in both estrogen receptor positive (MCF-7) and negative (MDA-MB-231) breast cancer cell lines. Cytochrome c release, activation of caspases-9, -8 and -7 and cleavage of poly (ADP-ribose) polymerase protein typified the apoptotic event and caspase inhibition revealed that PG acts via the mitochondrial pathway. In a multidrug-resistant subline of MCF-7 cells that over-expresses the breast cancer resistance protein, the cytotoxic activity of PG was slightly reduced. However, flow-cytometry analysis of PG accumulation and efflux in MCF-7 sublines showed that PG is not a substrate for this resistance protein. These results suggest that PG is an interesting and potent new pro-apoptotic agent for the treatment of breast cancer even when multidrug resistance transporter molecules are present.

Growth factors seem to be part of a complex cellular signalling language, in which individual growth factors are the equivalents of the letters that compose words. According to this analogy, informational content lies, not in an individual growth factor, but in the entire set of growth factors and others signals to which a cell is exposed. The ways in which growth factors exert their combinatorial effects are becoming clearer as the molecular mechanisms of growth factors actions are being investigated. A number of related extracellular signalling molecules that play widespread roles in regulating development in both invertebrates and vertebrates constitute the Fibroblast Growth Factor (FGF) and type beta Transforming Growth Factor (TGF beta). The latest research literature about the role and fate of these Growth factors and their influence in the craniofacial bone growth ad development is reviewed.

Prodigiosin (PG) is an active component of bacterial origin, with reported apoptotic effects. We examined the activation of caspases-9, -8, and -3 in PG-treated Jurkat cells in a dose-response study. These caspases were activated in apoptotic cells, as judged by the appearance of cleavage products from procaspases, and cytochrome c (cyt c) was released to the cytosol. In addition, PG induced the cleavage of poly (ADP-ribose) polymerase (PARP). This study demonstrates that the activation of caspases-9, -8, and -3 mediates PG-induced apoptosis.

The digestive tract of the tortoise Testudo graeca (Testudines) was investigated by means of light and electron microscopy. The esophagus of T. graeca was lined by two types of epithelium: non-keratinized stratified squamous in the upper portion and stratified columnar in the lower. The lamina propria of the esophagus contained tubular or tubuloacinar glands. The mucosa of the stomach showed similar characteristics to those of other reptiles. The small intestine exhibited longitudinal folds lined by absorptive and goblet cells. The large intestine was lined by columnar mucous cells. Within the lamina propria of the large intestine, masses of 10-15 epithelial cells connecting with the surface epithelium by means of slender cytoplasmic processes were observed. A battery of six lectins (Con-A, PNA, WGA, DBA, SBA, and LTA) was used to identify the epithelial mucins. WGA and DBA reacted with all types of mucous cells throughout the alimentary canal. PNA was only unreactive in the intestine, LTA in the esophagus, and SBA in the large intestine. These results indicate a similar lectin-binding pattern throughout the gut of T. graeca., (Copyright © 1990 Wiley-Liss, Inc.)

Little is known about the distribution of glycoproteins in the digestive tube of birds. In the present study, the localization and distribution of mucins in the digestive tract of the chicken are reported. Sialo- and sulpho-mucins were widely distributed throughout the chicken digestive tube. Some of the mucous cells of the proximal segment of the proventriculus presented neutral glycoproteins; in the medial segment, surface cells containing only sialo-mucins were observed. Surface cells of the gizzard contained both sialo- and sulpho-mucins while PAS-positive material was localized in the lumen of the glands. 2 types of mucous cells were observed in the small intestine; 1 type contained only sialo-mucins and the other contained both sialo- and sulpho-mucins. In the large intestine and caecum, both types of acid mucins were present in the mucous cells. In conclusion, the distribution of glycoproteins in the chicken reported in the present study show marked differences with that reported in other avian species.

In the present study, the distribution and characteristics of mucins in the digestive tract of 3 reptiles (Lacerta lepida, Mauremys caspica and Testudo graeca) are investigated. In the esophagus of Testudo graeca, both the glands and the mucous cells of the surface epithelium contained sulphosialo-mucins. In Lacerta lepida, esophageal mucous cells contained either-sialo-mucins or sulphosialo-mucins. The esophageal mucous cells of Mauremys caspica contained acidic mucosubstances. The stomach of the species studied revealed a small amount of acidic mucosubstances; in Lacerta lepida and Testudo graeca, abundant neutral mucins were detected. In the intestine, the amount of acidic mucosubstances was increased in a caudal direction, the sulphosialo-mucins being predominant. In conclusion, acid mucins were more abundant in the esophagus and intestine than in the stomach. This may be related to cytoprotective roles in the esophagus and protection against potential pathogens in the intestine.

The tracheal epithelium of Testudo graeca and Pseudemys scripta elegans was studied by means of light and electron microscopy, histochemistry and immunocytochemistry. Three cell types were detected by conventional light microscopy: mucous, ciliated and basal. The Grimelius silver argyrophil technique was positive in a population of tracheal cells. By immunocytochemistry, serotonin-containing cells were identified. The mucous cells of Testudo graeca contained sialomucins and sulphomucins; however, only sialomucins were detected in Pseudemys scripta elegans. By electron microscopy four cell types were observed: mucous, ciliated, basal and endocrine. Plasma cells were also found. The differences between the species studied lay mainly in the ultrastructure of the ciliated cells, the mucous granules and the presence of a special type of basal cell called 'clear basal cells' in non-hibernating specimens of Testudo graeca. During hibernation, the tracheal epithelium of Testudo graeca showed the following changes: (1) Myelin bodies were present in the cytoplasm. (2) The intercellular spaces were remarkably widened. (3) No 'clear basal cells' were present. In conclusion, the tracheal epithelium of the reptiles studied showed a pattern similar to that described in mammals but some differences from reptiles previously studied were found.

The lung of the tortoise, Testudo graeca (Chelonia) was studied by means of light and electron microscopy, histochemistry and immunocytochemistry. The lung showed the typical faviform structure of the reptilian lung. Three orders of trabeculae were observed. The epithelium of primary and secondary trabeculae was composed of ciliated, mucous, basal and endocrine cells. Mucous cells contained sialo- and sulpho-mucins and were reactive to the lectins Con-A, WGA, DBA, PNA and SBA. Endocrine cells were observed as solitary cells or forming neuroepithelial bodies. By means of immunocytochemistry, endocrine cells were demonstrated to contain serotonin. In the gas-exchange area Types I and II pneumonocytes and undifferentiated cells were observed. Free macrophages were detected in the faveolar lumen. The lung interstitium contained smooth muscle cells, fibrocytes, pigment cells, myelinated and unmyelinated nerves and intrapulmonary ganglia. Nerve terminals containing clear and dense-cored vesicles were observed in the adventitia of the blood vesicles and interspersed between the smooth muscle bands. The lung of the hibernating specimens showed a marked vacuolisation of pneumonocytes. In conclusion, the lung of Testudo graeca showed a complex histological organisation. Marked differences from mammalian lung were found.

The epithelium of the extrapulmonary airways of a Chelonia (Mauremys caspica) and a Squamata (Lacerta lepida) was investigated by means of conventional light and transmission electron microscopy, scanning electron microscopy, histochemistry and immunocytochemistry. The epithelium of Mauremys caspica is composed of basal, ciliated, endocrine and mucous cells. Serotonin-immunoreactivity was detected in the endocrine cells. Mucous cells were found to contain either sialo-mucins or both sialo- and sulphomucins. The extrapulmonary airways of Lacerta lepida were lined by an epithelium composed of basal, ciliated and secretory cells. No endocrine cells were detected. Secretory cells showed a different morphology to that observed in the mucous cells of Mauremys caspica suggesting a possible serous role for these cells. Migratory cells (plasma and mast cells, leucocytes and macrophages) and small intraepithelial nerves were also detected within the epithelium of both species. The present results show that marked morphological differences occur between the epithelia of the extrapulmonary airways of reptiles belonging to the genus Chelonia and Squamata.