VWCE Functions as a Tumor Suppressor in Breast Cancer Cells
FRONTIERS IN ONCOLOGY
Authors: Zhang, Dan; Wan, Lili; Yang, Fan; Liu, Wenlan; Liu, Litao; He, Shengnan; Xie, Ni
Abstract
Breast cancer remains a leading cause of cancer-related death, for which the majority of deaths result from metastases. Von Willebrand factor C and EGF domain (VWCE) is a member of the Von Willebrand factor (VWF) gene family; however, its function, regulatory mechanism, and clinical value in breast cancer remain unclear. In the present study, we sought to elucidate the role of VWCE in breast cancer metastasis. We examined the expression of VWCE in breast cancer tissues and normal control tissues of 50 breast cancer patients. We found that VWCE expression was downregulated in breast cancer cells and tissues compared to normal breast epithelial cells or the adjacent normal tissues. To explore the role of VWCE in human breast cancer development, we introduced a VWCE-overexpressing or control lentiviral vector into the breast cancer MDA-MB-453 and MDA-MB-231 lines in vitro. The overexpression of VWCE inhibited the proliferation, migration, invasion, and chemoresistance of the breast cancer cell lines. More importantly, the forced expression of VWCE suppressed tumor formation and metastasis in nude mice. iTRAQ-based quantitative proteomic analysis revealed that VWCE overexpression induced a 10-fold decrease in the level of WD-repeat domain 1 (WDR1) protein expression. Rescue experiments further verified that WDR1 was a downstream molecule of VWCE, and WDR1 overexpression reversed the above effects of VWCE overexpression on tumor growth. Therefore, VWCE may represent a novel tumor suppressor, for which its deregulation promotes breast cancer progression via the upregulation of WDR1.
Chromones and coumarins from Saposhnikovia divaricata (Turcz.) Schischk. Growing in Buryatia and Mongolia and their cytotoxicity
JOURNAL OF ETHNOPHARMACOLOGY
Authors: Urbagarova, Bayarma M.; Shults, Elvira E.; Taraskin, Vasilii V.; Radnaeva, Larisa D.; Petrova, Tatyana N.; Rybalova, Tatyana, V; Frolova, Tatyana S.; Pokrovskii, Andrey G.; Ganbaatar, Jamsranjav
Abstract
Ethnopharmacological relevance: Saposhnikovia divaricata (family Apiaceae) a traditional medicinal plant distributed in many provinces of China, is well known for the pharmaceutical value and has been used for rheumatic arthritis, and anxiety in children. Antiviral, antioxidant and antiproliferative activities were also mentioned. The application of this plant are recorded in the Chinese Medicine (CM) classical text the Shen Nong's Materia Medica (Shen Nong Ben Cao Jing). In this monograph S. divaricata (syn Radix Ledebouriella divaricata) is graded as a premium-grade herb, with their broad-spectrum of therapeutic applications for the treatment of cough, common cold, arthralgia, as well as in rheumatic disorders. Aim of the study: To isolate and identify chemical constituents (chromones and coumarins) from S. divaricata, collected in Buryatia and Mongolia and to study their in vitro anticancer activity against MEL-8, U-937, DU-145, MDA-MB-231 and BT-474 cell lines. Materials and methods: An 40% aqueous ethanol extract of the roots of S. divaricata was prepared and further successively fractionated by extraction with petroleum ether, diethyl ether, tert-butyl methyl ether and ethyl acetate. The obtained extracts were subjected to a series of chromatographic separations on silica gel for isolation of individual compounds. Isolated compounds were tested for their cytotoxicity with respect to model cancer cell lines using the conventional MTT assays. Results: Total of 15 individual compounds: coumarins scopoletin 2, bergapten 3, isoimperatorin 4, marmesin 5, (+)-decursinol 9, (-)-praeruptorin B 10, oxypeucedanin hydrate 11, chromones: hamaudol 6, cimifugin 7, 5-O-methylvisamminol 8, chromone glycosides: prim-Oglucosylcimifugin 12, sec-O-glucosylhamaudol 13, 4'-O-beta-D-glucopyranosyl-5-O-methylvisamminol 14, 4'-O-beta D-glucopyranosylvisamminol (15) and also polyyne compound panaxinol 1 were isolated and characterized. The structure of dihydropyranocoumarin 10 was confirmed by X-ray diffraction analyses. HPLC-UV method was used for determination of the content of most abundant chromones 7, 12 and 14 in the roots of S. divaricata, collected in Mongolia. Compounds 3-11 and 13, 14 were evaluated for their cytotoxicity with respect to model cancer cell lines. All the compounds were non-toxic in the hemolysis test. Conclusion: This report about the phytochemical profiles of S. divaricata growing in Mongolia and Buryatia led to the identification of 14 compounds including coumarins and chromones. The available coumarins and chromones may serve as new leads for the discovery of anticancer drugs.