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Life Sci. 2016 Apr 15;151:264-276. doi: 10.1016/j.lfs.2016.03.024. Epub 2016 Mar 12.

A novel bisindole-PBD conjugate inhibits angiogenesis by regulating STAT3 and VEGF in breast cancer cells.

Author information

1
Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
2
Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India; School of Chemical & Biotechnology, SASTRA University, Tirumalaisamudram, Thanjavur 613401, India.
3
Functional Genomics and Gene Silencing Group, CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500007, India.
4
Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India. Electronic address: manikapb@gmail.com.

Abstract

AIMS:

Breast cancer is highly resistant to chemotherapeutic approach and hence, alternative strategies have been developed to fight against this heterogeneous group of disease. In particular, many studies have demonstrated about various drugs for the treatment of breast cancer. In our study, we assessed the anti-angiogenenic activities of Bisindole-PBD (5b) in MCF-7 and MDA-MB-231 cell lines.

MAIN METHODS:

In vitro Endothelial Cell (HUVEC) Tube Formation Assay was performed to show inhibitory role of 5b along with its role upon wound healing process in breast cancer cells in vitro. Semi-quantitative reverse transcription PCR (RT-PCR) was also done to examine the expression of VEGF in response to 5b in breast cancer cells and in HUVEC cells. siRNA transfection study explored STAT3 mediated VEGF transcription in breast cancer cells MCF-7 and MDA-MB-231. CAM assay was performed to see the role of 5b on vessel formation in chicken embryo.

KEY FINDINGS:

From in vitro data we have demonstrated that 5b played a role in regulation of breast cancer cell proliferation by inhibiting angiogenesis. Test drug 5b suppressed the expression VEGF at both transcriptional and post transcriptional levels. Apart from this, there was significant down regulation in STAT3 level after drug treatment, which was found to be involved in the VEGF transcription. Metastasis related MMP-2 and MMP-9 expressions were also modulated by 5b. In vivo study by Chick Chorioallantoic Membrane (CAM) Assay also showed anti-angiogenesis role of the test drug which was consistent with the in vitro data.

SIGNIFICANCE:

Altogether, our data demonstrated 5b as potent small molecule with anti-angiogenic activities.

KEYWORDS:

Angiogenesis; Bisindole-PBD (5b); Breast cancer; CAM assay; STAT3; VEGF

PMID:
26979778
DOI:
10.1016/j.lfs.2016.03.024
[Indexed for MEDLINE]

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