An azaspirane derivative suppresses growth and induces apoptosis of ER-positive and ER-negative breast cancer cells through the modulation of JAK2/STAT3 signaling pathway

  • Authors:
    • Nurfarhanah Bte Syed Sulaiman
    • Chakrabhavi Dhananjaya Mohan
    • Salundi Basappa
    • Vijay Pandey
    • Shobith Rangappa
    • Hanumantharayappa Bharathkumar
    • Alan Prem Kumar
    • Peter E. Lobie
    • Kanchugarakoppal S. Rangappa
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  • Published online on: July 6, 2016     https://doi.org/10.3892/ijo.2016.3615
  • Pages: 1221-1229
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Abstract

Persistent activation of signal transducer and activator of transcription 3 (STAT3) is associated with the progression of a range of tumors. In this report, we present the anticancer activity of 2-(1-(4-(2-cyanophenyl)1-benzyl‑1H-indol-3-yl)-5-(4-methoxy-phenyl)-1-oxa-3-azaspiro(5,5)undecane (CIMO) against breast cancer cells. We observed that CIMO suppresses the proliferation of both estrogen receptor-negative (ER-) (BT-549, MDA-MB‑231) and estrogen receptor-positive (ER+) (MCF-7, and BT-474) breast cancer (BC) cells with IC50 of 3.05, 3.41, 4.12 and 4.19 µM, respectively, and without significantly affecting the viability of normal cells. CIMO was observed to mediate its anti-proliferative effect in ER- BC cells by inhibiting the phosphorylation of JAK2 and STAT3 proteins. Quantitative PCR analysis demonstrated that CIMO decreases the relative mRNA expression of genes that are involved in cell cycle progression (CCND1) and cell survival (BCL2, BCL-xL, BAD, CASP 3/7/9, and TP53). In addition, CIMO was observed to arrest BC cells at G0/G1 phase and of the cell cycle. Furthermore, CIMO suppressed BC cell migration and invasion with concordant regulation of genes involved in epithelial to mesechymal transition (CDH1, CDH2, OCLN and VIM). Thus, we report the utility of a synthetic azaspirane which targets the JAK-STAT pathway in ER- BC.
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September 2016
Volume 49 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Sulaiman, N.B., Mohan, C.D., Basappa, S., Pandey, V., Rangappa, S., Bharathkumar, H. ... Rangappa, K.S. (2016). An azaspirane derivative suppresses growth and induces apoptosis of ER-positive and ER-negative breast cancer cells through the modulation of JAK2/STAT3 signaling pathway. International Journal of Oncology, 49, 1221-1229. https://doi.org/10.3892/ijo.2016.3615
MLA
Sulaiman, N. B., Mohan, C. D., Basappa, S., Pandey, V., Rangappa, S., Bharathkumar, H., Kumar, A. P., Lobie, P. E., Rangappa, K. S."An azaspirane derivative suppresses growth and induces apoptosis of ER-positive and ER-negative breast cancer cells through the modulation of JAK2/STAT3 signaling pathway". International Journal of Oncology 49.3 (2016): 1221-1229.
Chicago
Sulaiman, N. B., Mohan, C. D., Basappa, S., Pandey, V., Rangappa, S., Bharathkumar, H., Kumar, A. P., Lobie, P. E., Rangappa, K. S."An azaspirane derivative suppresses growth and induces apoptosis of ER-positive and ER-negative breast cancer cells through the modulation of JAK2/STAT3 signaling pathway". International Journal of Oncology 49, no. 3 (2016): 1221-1229. https://doi.org/10.3892/ijo.2016.3615