Abstract:
Aberrant gene function and altered signalling pathways are closely linked with the proliferation, metastasis, and angiogenesis of tumour cells, which result in the transition of cancer cells from their site of origin to other parts of the body. Through modulating JAK/STAT3 activation in breast cancer cell lines, we have looked into the mechanism of Pilea umbrosa methanol (PUM) extract anticancer potential. Anti-proliferative and apoptotic potential of PUM extract was determined against various breast cancer cells, through MTT and Flow cytometry analysis. Cells were analyzed through transwell and invasion matrigel system for their metastatic potential against PUM extract. Finally, Western blotting used to analyze the protein expression of apoptotic and STAT3 signaling pathway. We found that PUM, at concentrations as low as 25 µg/ml, suppressed the growth of several breast cancer cell lines including MDA-MB-231, and Mcf-7 cells. PUM induces apoptosis and triggers cell cycle arrest, which can be correlated with its ability to downregulate the expression of cleaved caspase-9/3/7/8, PARP, pro-apoptotic proteins Bax, Bak, Bid, and cytochrome-c, and upregulate the expression of Cyclin D1, Cyclin E, VEGF, COX-2, metastatic protein MMP-9/2, anti-apoptotic proteins Bcl-2, Mcl-1, Survivin, and XIAP in a concentration-dependent manner. The underlying mechanism of PUM-induced apoptosis was preceded by the suppression of constitutive STAT3 signalling in MDA-MB-231 cells in a time-dependent manner. STAT3 suppression was mediated through inhibition of upstream Janus-activated kinases (JAK1 and JAK2) and c-Src protein, suggesting the involvement of tyrosine kinases. The inhibition of STAT3 via Stattic inhibitor (SC-203282) reverses the PUM-inhibited proliferation, induces apoptosis, cell cycle arrest and abrogates angiogenesis in the MDA-MB-231 cell line. Indeed, we found that PUM also induced the expression of tyrosine phosphatase of Protein Inhibitor of Activated STAT3 (PIAS-3) that is correlated with the down-regulation of constitutive STAT3 activation in MDAMB-231 cells. Our results conclude the anticancer effect of PUM through inhibition of STAT3 pathway in MDA-MB-231 cell lines. Further, PUM-induced apoptosis in suitable animal models would be an encouraging and promising research area. Abbreviations: Single transducer and activator of transcription 3 (STAT3), X-linked inhibitor of apoptosis protein (XIAP), Poly (ADP-ribose) polymerase) (PARP), Bcl-2 homologous antagonist/killer (BAK), Bcl-2-Associate X protein (BAX), B-cell lymphoma-extra-large (BCLXL), 3-(4, 5-Dimethylthiazol-2-yl)_2,5 diphenyltetrazoliumbromide (MTT), Matrix metalloproteinases-2/9 (MMP-2/9).
Page(s):
118-118
DOI:
DOI not available
Published:
Journal: Abstract Book on Global Science Technology and Management Conference, Volume: 0, Issue: 0, Year: 2023
Keywords:
Metastasis
,
Apoptosis
,
Malignant Cells
,
Targeting STAT3 Signaling Pathway
,
Pilea Umbrosa