Anti-angiogenic and pro-apoptotic effects of a small-molecule JFD-WS in in vitro and breast cancer xenograft mouse models

  • Authors:
    • Appu Rathinavelu
    • Thanigaivelan Kanagasabai
    • Sivanesan Dhandayuthapani
    • Khalid Alhazzani
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  • Published online on: February 9, 2018     https://doi.org/10.3892/or.2018.6256
  • Pages: 1711-1724
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Abstract

A small molecule that was developed for blocking vascular endothelial growth factor receptor 2 (VEGFR2) has been tested and confirmed for its anti-angiogenic activity. Subsequently, it was modified into a water soluble salt form (JFD-WS) to increase bioavailability and distribution during in vivo pre-clinical testing. The present study was designed to further evaluate the anti-angiogenic and pro-apoptotic effects of JFD-WS in monotherapy as well as in combination with paclitaxel (Taxol) using a mouse xenograft model. The in vitro anti-angiogenic effects of JFD-WS were investigated using cell proliferation, migration, Matrigel tube formation and VEGFR2 phosphorylation assays. The anti-angiogenic effect of JFD-WS was further established using chorioallantoic membrane (CAM) assay followed by in vivo efficacy testing on GI-101A breast adenocarcinoma cells. Pharmacokinetic and toxicity studies were performed using BALB/c mice. Finally, the apoptotic signals were assessed in the control and experimental tumor samples, and the plasma mucin 1 (MUC1) levels were analyzed. In the in vitro tests, JFD-WS effectively inhibited HUVEC proliferation, migration, tube formation and VEGFR2 phosphorylation. Additionally, JFD-WS inhibited the formation of blood vessels in chick chorioallantoic membrane. While inhibiting the xenograft tumor growth in experimental mice, JFD-WS decreased the plasma MUC1 levels. The western blot analysis of apoptotic markers and fragmentation analysis of DNA confirmed the pro-apoptotic effects of JFD-WS. These results indicated that JFD-WS alone or in combination with paclitaxel exerted antitumor and pro-apoptotic effects in the breast cancer xenograft model due to an anti-angiogenic effect. These results strongly support the clinical translation of its use.
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April 2018
Volume 39 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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APA
Rathinavelu, A., Kanagasabai, T., Dhandayuthapani , S., & Alhazzani, K. (2018). Anti-angiogenic and pro-apoptotic effects of a small-molecule JFD-WS in in vitro and breast cancer xenograft mouse models. Oncology Reports, 39, 1711-1724. https://doi.org/10.3892/or.2018.6256
MLA
Rathinavelu, A., Kanagasabai, T., Dhandayuthapani , S., Alhazzani, K."Anti-angiogenic and pro-apoptotic effects of a small-molecule JFD-WS in in vitro and breast cancer xenograft mouse models". Oncology Reports 39.4 (2018): 1711-1724.
Chicago
Rathinavelu, A., Kanagasabai, T., Dhandayuthapani , S., Alhazzani, K."Anti-angiogenic and pro-apoptotic effects of a small-molecule JFD-WS in in vitro and breast cancer xenograft mouse models". Oncology Reports 39, no. 4 (2018): 1711-1724. https://doi.org/10.3892/or.2018.6256