• Biomedical Science Letters
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• v.20 no.2
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• pp.49-55
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• 2014

RalBP1 is an ATP-dependent non-ABC transporter, responsible for the major transport function in many cells including many cancer cell lines, causing efflux of glutathione-electrophile conjugates of both endogenous metabolites and environmental toxins. RalBP1 is expressed in most human tissues, and is over-expressed in non-small cell lung cancer cell lines and in many other tumor types. Blockade of RalBP1 by various approaches has been shown to increase sensitivity to radiation and chemotherapeutic drugs, leading to cell apoptosis. In xenograft tumor models in mice, RalBP1 blockade or depletion results in complete and sustained regression across many cancer cell types including lung cancer cells. In addition to its transport function, RalBP1 has many other cellular and physiological functions, based on its domain structure which includes a unique Ral-binding domain and a RhoGAP catalytic domain, as well as docking sites for multiple signaling proteins. Additionally, RalBP1 is also important for stromal cell function in tumors, as it was recently shown to be required for efficient endothelial cell function and angiogenesis in solid tumors. In this review, we discuss the cellular and physiological functions of RalBP1 in normal and lung cancer cells.

• Polymer(Korea)
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• v.32 no.6
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• pp.561-565
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• 2008

Hyaluronic acid (HA) is a natural glycosaminoglycan and is used widely in the pharmaceutical field. Lipoic acid (LA) helps the regeneration of exogenous and endogenous antioxidants such as Vitamin C and Vitamin E as well as glutathione. It also acts as antioxidant indirectly. Hydrophilic HA as a biodegradable and biocompatible polymer was conjugated with hydrophobic LA as an antioxidant to form the graft copolymer. The carboxyl group of HA was modified by adipic acid dihydrazide (ADH). The synthesis of HA-g-LA graft copolymers was characterized by FT-IR, $^1H$-NMR spectroscopy. The conjugates could form the self-assembled nanoparticles in aqueous solution. The particle size and critical aggregation concentration were verified to use the nanoparticle as a carrier fur the hydrophobic material.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4981-4985
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• 2015

Background: Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. Targeting autophagic cell death is emerging as a novel strategy in cancer chemotherapy. Aldose reductase (AR) catalyzes the rate limiting step of the polyol pathway of glucose metabolism; besides reducing glucose to sorbitol, AR reduces lipid peroxidation-derived aldehydes and their glutathione conjugates. A complex interplay between autophagic cell death and/or survival may in turn govern tumor metastasis. This exploratory study aimed to investigate the potential role of AR inhibition using a novel inhibitor Fidarestat in the regulation of autophagy in CRC cells. Materials and Methods: For glucose depletion (GD), HT-29 and SW480 CRC cells were rinsed with glucose-free RPMI-1640, followed by incubation in GD medium +/- Fidarestat ($10{\mu}M$). Proteins were extracted by a RIPA-method followed by Western blotting ($35-50{\mu}g$ of protein; n=3). Results: Autophagic regulatory markers, primarily, microtubule associated protein light chain (LC) 3, autophagy-related gene (ATG) 5, ATG 7 and Beclin-1 were expressed in CRC cells; glyceraldehyde-3 phosphate dehydrogenase (GAPDH) was used as an internal reference. LC3 II (14 kDa) expression was relatively high compared to LC3A/B I levels in both CRC cell lines, suggesting occurrence of autophagy. Expression of non-autophagic markers, high mobility group box (HMG)-1 and Bcl-2, was comparatively low. Conclusions: GD +/- ARI induced autophagy in HT-29 and SW-480 cells, thereby implicating Fidarestat as a promising therapeutic agent for colorectal cancer; future studies with more potent ARIs are warranted to fully dissect the molecular regulatory networks for autophagy in colorectal carcinoma.

• Natural Product Sciences
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• v.9 no.2
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• pp.68-72
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• 2003

Quercetin and its sugar conjugates are the most abundantly distributed bioflavonoids and represent the largest proportion of flavonols in the plant kingdom. The present study was undertaken to demonstrate the effect of quercetin on the role of reactive oxygen species (ROS) in the development of gastric ulcers in rats. Administration of quercetin in doses of 50, 100 and $200\;mg\;kg^{-1}$ twice daily for 5 days, showed dose dependent significant protection against ethanol (EtOH), aspirin (ASP), cold-restraint stress (CRS) and pylorus ligation (PL) -induced gastric ulcer models and the results were comparable with those elicited by sucralfate. The thiobarbituric acid reactive substances in the stomach mucosa, an index of lipid peroxidation and regulation of plasma corticosterone were significantly increased in CRS-induced gastric ulceration. The queroetin $(100\;mg\;kg^{-1})$ and reduced glutathione effectively inhibited gastric lesions induced by CRS with a significant decrease in the lipid peroxidation and plasma corticosterone. These results indicate that quercetin a bioflavonoid exerts its antiulcer effect in light of free radical scavenging and plasma corticosterone in cold restraint stress ulcers.