Photochemical internalization (PCI) is a unique procedure for site‐specific delivery of several types of membrane‐impermeable molecules to the cytosol of target cells. The technology is based on photochemical‐induced release of endocytosed macromolecules from endosomes and lysosomes into the cytosol. The purpose of this study was to evaluate the therapeutic potential of PCI of the type I ribosomal‐inactivating protein gelonin in an animal model. The photosensitizer aluminum phthalocyanine disulfonate (AlPcS2a) was injected intraperitoneally (10 mg/kg) into athymic female BALB/c (nu/nu) nude mice (8–9 mice per group) with subcutaneously growing human adenocarcinoma (WiDr) tumors 48 hr before exposure to 135 J/cm2 of red light focused on the tumor. Six hours before light exposure a single dose of 50 μg gelonin was administrated intratumorally. Tumor growth was measured at least twice a week. After immunomagnetic separation of in vivo growing tumor cells the subcellular localization of the photosensitizer was evaluated by fluorescence microscopy. The photosensitizer localized in endocytic vesicles in in vivo growing WiDr cells. Furthermore, it was found that in vitro gelonin treatment of WiDr cells isolated from photosensitizer‐treated mice potentiated a light‐induced decrease of clonal survival. Complete remission in 6 of 9 (67%) of the treated mice were induced. Our findings indicate that photochemical treatment with the photosensitizer AlPcS2a activates the cytotoxic potential of gelonin in vivo. These results demonstrate that the synergistic effect of combining photoactivation of photosensitizer located in endocytic vesicles and gelonin is indeed a result of PCI of gelonin. © 2001 Wiley‐Liss, Inc.
Louis Pasteur was the first to describe the antibacterial effect of onion and garlic juices. Historically, garlic has been used worldwide to fight bacterial infections. Allium vegetables, particularly garlic (Allium sativum L.) exhibit a broad antibiotic spectrum against both gram-positive and gram-negative bacteria. Noteworthy results published include the following: 1) raw juice of garlic was found to be effective against many common pathogenic bacteria-intestinal bacteria, which are responsible for diarrhea in humans and animals; 2) garlic is effective even against those strains that have become resistant to antibiotics; 3) the combination of garlic with antibiotics leads to partial or total synergism; 4) complete lack of resistance has been observed repeatedly; 5) even toxin production by microorganisms is prevented by garlic. Helicobacter pylori (H. pylori) is a bacterium implicated in the etiology of stomach cancer and ulcers. The incidence of stomach cancer is lower in populations with a high intake of allium vegetables. We have demonstrated in vitro that H. pylori is susceptible to garlic extract at a fairly moderate concentration. Even some antibiotic-resistant H. pylori strains are susceptible to garlic. Clinical trials are necessary to explore the possibility of using garlic as a low-cost remedy for eradicating H. pylori.
Gastric cancer is the major cancer in the developing world and one of the top two worldwide. Helicobacter pylori is a bacterium implicated in the etiology of stomach cancer. The incidence of stomach cancer is lower in individuals and populations with high Allium vegetable intakes. Allium vegetables, particularly garlic, have antibiotic activity. Standard antibiotic regimens against H. pylori are frequently ineffective in high-risk populations. As part of our study of the role of Allium vegetable intake on cancer prevention, we wished to investigate its antimicrobial activity against H. pylori. An aqueous extract of garlic cloves was standardized for its thiosulfinate concentration and tested for its antimicrobial activity on H. pylori grown on chocolate agar plates. Minimum inhibitory concentration was 40 micrograms thiosulfinate per milliliter. Staphylococcus aureus tested under the same conditions was not susceptible to garlic extract up to the maximum thiosulfinate concentration tested (160 micrograms/ml). To our knowledge, this is the first report of H. pylori's susceptibility to garlic extract of known thiosulfinate concentration. It is plausible that the sensitivity of H. pylori to garlic extract at such low concentration may be related to the reported lower risk of stomach cancer in those with a high Allium vegetable intake. Furthermore, it may identify a strategy for a low-cost intervention, with few side effects, in populations at high risk for stomach cancer, particularly where antibiotic resistance and the risk of reinfection are high.
Photochemical internalisation (PCI) was recently demonstrated as a unique procedure for site‐specific delivery of several types of membrane impermeable macromolecules from endocytotic vesicles to the cytosol (Berg et al., 1999). The technology is based on the cytosolic release of endocytosed macromolecules from endosomes and lysosomes upon exposure of cells to photosensitising compounds, which became localised to these vesicles, and light. In our study the possibility to increase the cytotoxic effect of the immunotoxin MOC31‐gelonin by PCI was examined. The type I ribosome‐inactivating protein gelonin was covalently linked to the monoclonal IgG1 antibody MOC31, directed against epithelial glycoprotein‐2 (EGP‐2), an antigen expressed on most carcinoma cells. Five different cell lines, of which 4 expressed EGP‐2, were treated with MOC31‐gelonin and endosomal and lysosomal localising photosensitisers, followed by exposure to light. Insignificant cytotoxicity of the MOC31‐gelonin was observed when the cells were incubated with the immunotoxin alone. However, in combination with endosomal and lysosomal localising photosensitizers, we demonstrate synergistic toxic effect of the MOC31‐gelonin conjugate in a light‐dependent manner. Our results indicate that PCI is a promising tool for increasing the cytotoxicity of immunotoxins, which is important for further improvement of the PCI concept towards possible use in cancer therapy. Int. J. Cancer 87:853–859, 2000. © 2000 Wiley‐Liss, Inc.
Background/aims-Iron overload can cause liver toxicity and increase the risk of liver failure or hepatocellular carcinoma in humans. Curcumin (diferuloylmethane), a component of the food spice turmeric, has antioxidant, iron binding, and hepatoprotective properties. The aim of this study was to quantify its effects on iron overload and resulting downstream toxic effects in cultured T51B rat liver epithelial cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.