Abstract 1380: The in vivo activity of a novel anti-angiogenic compound, JFD-WS, in human breast adenocarcinoma xenograft implanted athymic nude mice
Authors: Thanigaivelan Kanagasabai, Janelle Alvarez, Meera Bhalani, Sivanesan Dhandayuthapani, Appu Rathinavelu
Journal: Cancer Research (2015)

Abstract The tumor growth and metastasis of several cancers depend on the extent of both angiogenesis and lymphangiogenesis triggered by chemical signals that are originating from cancer cells with aggressive growth ability. The discovery of angiogenic inhibitors have been helping to reduce both morbidity and mortality resulting from multiple types of cancers. As part of the comprehensive treatment strategy combining anti-angiogenic agents with conventional cytoreductive treatments is considered to be the most effective approach. As part of this strategy an added ability for inducing apoptosis in cancer cells could make the therapeutic agents very effective. The in vitro anti-angiogenic activity of water soluble form of JFD (JFD-WS) was examined by ECMatrixTM gel assay with human umbilical vein endothelial cells (HUVEC) using 0.01-10 μM concentrations at different time intervals (0, 4 and 8 hrs). A complete inhibition of in vitro angiogenesis was observed in 8 hrs at 10 μM concentration of JFD-WS. Our newly discovered JFD-WS is also proven as a potent anti-cancer drug in this study by using GI-101A (human breast adenocarcinoma) xenograft implanted athymic nude mice. In addition to the anti-angiogenic ability, the anti-tumor activity of JFD-WS seems to be further enhanced due to induction of apoptosis in the xenograft tumor implanted animals. In addition, the intraperitoneal (i.p.) injection of JFD-WS (at a dose of 100 mg/kg body weight) was able to significantly inhibit the tumor growth compared to the control group. At the end of the treatment period 35.19% inhibition of tumor growth was observed in JFD-WS treated animals along with prolongation of survival. The tumor inhibition was lot more effective when JFD-WS was combined with Taxol (10 mg/kg). The analysis of MUC1 levels in the serum proved a significant regression of the tumor burden in the experimental animals. Furthermore, when the key apoptotic signaling molecules such as Bax, Bcl2, Cytochrome c, Apaf-1, cleaved caspase-3 and p53 were analyzed in the tumor samples, that were extracted from JFD-WS treated animals. A significant increase in the expression of Bax (10.6 fold), Apaf-1 (2.2 fold), and p53 (3 fold) were observed. In support of the induction of apoptotic signals, the expression of anti-apoptotic protein Bcl2 was decreased by 1.8 fold. Consequently, the release of Cytochrome c found in the cytosolic fraction was significantly higher in JFD-WS treated animals as compared with the untreated controls. Finally, the induction of apoptosis in JFD-WS treated group was confirmed by the presence of cleaved caspase-3. Our results from both in vivo and in vitro experiments confirm the anti-angiogenic and pro-apoptotic effects of JFD-WS in xenograft tumor implanted athymic nude mice (This project was supported by The Royal Dames of Cancer Research Inc., Ft.Lauderdale, Florida). Citation Format: Thanigaivelan Kanagasabai, Janelle Alvarez, Meera Bhalani, Sivanesan Dhandayuthapani, Appu Rathinavelu. The in vivo activity of a novel anti-angiogenic compound, JFD-WS, in human breast adenocarcinoma xenograft implanted athymic nude mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1380. doi:10.1158/1538-7445.AM2015-1380