• Environmental Analysis Health and Toxicology
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• v.13 no.3_4
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• pp.87-94
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• 1998

The use of cisplatin is limited by severe side effects such as renal toxicity. Our platinum-base drug discovery is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (II) complex analogue [Pt (cis-DACH)(DPPP)]. 2NO$_3$ (PC) containing cis-1,2-diaminocyclohexane as a carrier ligand and 1,3-bis(diphenylphosphino) propane as a leaving group. Furthermore, nitrate was added to improved the solubility. In this study, its structure was determined and its antitumor activity against SKOV-3 and NIH-OVCAR-3 human ovarian adenocarcinoma, and in vitro cytotoxicity was determined against primary cultured rabbit kidney proximal tubular and renal cortical cells of human kidney using colorimetric MTT assay. PC demonstrated acceptable antitumor activity against SKOV-3 and NIH-OVCAR-3 human ovarian adenocarcinoma and significant activity as compared with that of cisplatin. The toxicity of PC was found quite less than that of cisplatin using MTT and $^3$H-thymidine uptake tests in rabbit proximal tubular cells and human kidney cortical cells. PC was used for human cortical tissue in 7 weeks hitoculture by the glucose-consumption tests. We determined that the new platinum drug has lower nephrotoxicity than cisplatin. Based on these results, this novel platinum (II) complex compound (PC) represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low nephrotoxicity.

• Journal of Life Science
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• v.21 no.6
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• pp.767-774
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• 2011

Cell migration plays a fundamental role in cancer cell invasion and metastasis as well as in many physiological responses. Here, we screened four different sources of garlic - water extract of normal and black garlic, as well as dried normal and black garlic - for the identification of anti-invasive and anti-metastatic activity on cancer cells. Inhibition of cancer cell migration was observed in the hexane extract of dried-garlic. Inhibitory activity was further purified to near homogeneity by thin layer chromatography and named $\b{i}$nhibitor of $\b{c}$ancer $\b{m}$etastasis from garlic #27 (ICMG-27). ICMG-27 completely blocked insulin-like growth factor-1 (IGF-1)-induced OVCAR-3 cell migration at 6 ${\mu}g/ml$. ICMG-27 completely blocked IGF-1-induced OVCAR-3 and NIH-3T3 cell migration whereas IGF-1-induced mouse embryonic fibroblast (MEF) cell migration was not affected byICMG-27. ICMG-27 inhibited all the tested IGF-1-induced cancer cell migration such as OVCAR-3, SKOV-3, and MDA-MB-231 cells. Finally, ICMG-27 could inhibit IGF-1-, lysophosphatidic acid (LPA)-, sphingosine-1-phosphate (S1P)-, leukotriene B4 (LTB4)-, and angiotensin II (AngII)-induced OVCAR-3 cell migration. These results indicate that ICMG-27 inhibits cancer cell migration by blocking essential steps in many agonists-induced cancer cell migrations. Unveiling an anti-invasive mechanism of ICMG-27 on cancer cells will provide a basis for cancer therapy.

• The Journal of Internal Korean Medicine
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• v.32 no.1
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• pp.33-42
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• 2011

Background : Despite recent advances in cancer management, prognosis of ovarian cancer is poor. Anticancer effects of herbal medicine, such as Euonymus alatus Sieb, Oldenlandia diffusa (Willd.) Roxburgh, and Orostachys japonicus A. Berger, have been reported in treatment of ovarian and cervical cancers, but the systematic approaches to explain their molecular mechanism(s) have not yet been established. Objectives : To establish a basis of understanding for anti-cancer mechanisms of herbal medicine, we profiled protein expression in human ovarian and cervical cancer cells treated with the extracts from Euonymus alatus Sieb, Oldenlandia diffusa (Willd.) Roxburgh and Orostachys japonicus A. Berger. Methods : Human ovarian cancer cell line NIH:OVCAR-3, and human cervical cancer cell line HeLa were employed in the present study. Whole protein was obtained from the cells harvested at 48 hours after the treatment with herbal water-extract, and analyzed by 2DE-based proteomic approach. Results : Various changes of protein expression induced by the herbal treatment were monitored : down-regulation of molecular chaperone (calreticulin variant), glycolytic enzymes (D-3-phosphoglycerate dehydrogenase, glyceraldehyde 3-phosphate dehydrogenase and alpha-enolase), RNA processing molecules (hnRNP A2/B1), and antioxidant protein (peroxiredoxin 1). Conclusions : Repression of glycolysis has been accepted as the mechanism to increase anticancer reagent's effect. Thus, down-regulation of glycolytic enzymes by the herbal extracts suggested a possible synergistic effect of herbs in the presence of platinum-based therapeutics. In further study, as well as the synergistic effect of the herbs, it has to be further validated whether artificial regulation of hnRNP A2/B1 in ovarian cancer cells affects various cancer survival factors, since RNA processing can be interrupted by deranged expression of hnRNP subtypes, and it results in an inhibition of cancer cell growth.