Zero Hunger (SDG 2), Good Health & Well-being (SDG 3)
Pilea umbrosa induces apoptosis and inhibits metastasis in malignant cells through mediating c-Jun N-terminal kinase and targeting STAT3 signaling pathway
Irum Naz* The Islamia University of Bahawalpur, Pakistan
Aberrant gene function and altered signalling pathways such as signal transducer and activator of transcription 3 (STAT3) and JNK/MAPK are closely linked with the growth and colonization of tumour cells. Thus, an agent that can antagonize these signaling pathway could be a promising candidate for cancer treatment. In the current study, we investigated the effect of Pilea umbrosa methanol extract (PUM) in breast and hepatocellular carcinoma (HCC) cell lines. We observed that PUM treatment induced antiproliferative, pro-apoptotic and antimetastatic effect in MDA-MB-231 and HCCLM3 cells. The observed effect of PUM could be related to its ability to downregulate the protein expression of cleaved caspase-9/-3, PARP, Bcl-2, Mcl-1, Survivin, XIAP, Cyclin D1, Cyclin E, and MMP-9/-2 in parallel with the upregulation of Bax, Bak and Bid. Notably, we observed that PUM modulated the activation of STAT3 signalling cascade, which is mediated through blocking upstream Janus-activated kinases (JAK1 and JAK2) and c-Src and by increasing the activation of Protein Inhibitor of Activated STAT3 (PIAS-3) expression in MDA-MB-231 cells. Moreover, PUM induced the antiproliferative effect through increasing protein expression of JNK/MAPK in HCCLM3 cells. Indeed, we also found that the inhibition of STAT3 via Stattic inhibitor (SC-203282) and JNK via JNK inhibitor (SP610025) reverses the PUM mediated apoptosis in breast and HCC cells, respectively. Our results concluded that the anticancer effect of PUM is mediated through modulation of multiple signaling cascades; therefore, it may be a suitable candidate for the development of an anticancer drug. Key words: Pilea umbrosa; apoptosis; inhibitor; metastasis; HCCLM3; MDA-MB-231
P30
© The Author(s), 2023
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