Dataset Information

Inhibition of Stat3 Signaling Pathway by Natural Product Pectolinarigenin Attenuates Breast Cancer Metastasis.

ABSTRACT: Background: Breast cancer is the most common female cancer with considerable metastatic potential, which urges the need for developing novel potential drug candidate to inhibit tumor metastasis. Signal transducer and activator of transcription 3 (Stat3) have critical roles in cancer growth and metastasis and have been confirmed as a promising anticancer target. Here, we report our finding with pectolinarigenin, a flavonoid compound isolated from the aerial parts of Cirsium chanroenicum. Methods: The role of Pec. in cell proliferation, cell apoptosis, and cell migration and invasion in three breast cancer cells (4T1, MDA-MB-231, MCF-7) was investigated. Cell proliferation was determined by MTT assay, cell apoptosis was determined by flow cytometry, and protein expression was detected by western blotting. Tumor xenograft mice model and breast tumor metastasis model in vivo were built to further assess the effects of Pec. on 4T1 cells. Results: Intraperitoneal administrations of pectolinarigenin significantly inhibited breast cancer metastasis to lungs without affecting the tumor growth of incubated 4T1 breast cancer cells. Pectolinarigenin could also recruit CD8+ T cells to mediate tumor immune response. Furthermore, pectolinarigenin markedly impaired cancer cell migration and invasion by down-regulating phosphorylated-Stat3, and expression of matrix metalloproteinase (MMP)-2, MMP-9, while up-regulating the expression of TIMP2. We also found that pectolinarigenin inhibited breast cancer cell proliferation and induced apoptosis via mitochondrial-related apoptosis pathway, reduced mitochondrial membrane potential and the expression of Bcl-2, increased expression of Bax, and cleaved caspase-3 as well as disturbed the ROS generation. Conclusions: Pectolinarigenin might potentially be a candidate for metastasis of breast cancer by mediating Stat3 pathway.

SUBMITTER: Li Y

PROVIDER: S-EPMC6796319 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Inhibition of Stat3 Signaling Pathway by Natural Product Pectolinarigenin Attenuates Breast Cancer Metastasis.

Li Yali Y Gan Cailing C Zhang Yange Y Yu Yan Y Fan Chen C Deng Yuanle Y Zhang Qianyu Q Yu Xi X Zhang Yiwen Y Wang Liqun L He Fang F Xie Yongmei Y Ye Tinghong T Yin Wenya W

Frontiers in pharmacology 20191010

<b>Background:</b> Breast cancer is the most common female cancer with considerable metastatic potential, which urges the need for developing novel potential drug candidate to inhibit tumor metastasis. Signal transducer and activator of transcription 3 (Stat3) have critical roles in cancer growth and metastasis and have been confirmed as a promising anticancer target. Here, we report our finding with pectolinarigenin, a flavonoid compound isolated from the aerial parts of <i>Cirsium chanroenicum ...[more]

PMID: 31649548

Similar Datasets

Project description:As the current clinical treatment of acetaminophen (APAP)‑induced liver injury (AILI) has its limitations, new and effective treatment methods are required. Fingolimod (FTY720) is an immunosuppressive drug developed in recent years that has been shown to have a protective effect against ischemia/reperfusion liver injury. However, the role of FTY720 in AILI remains unclear. The aim of the present study was to determine whether FTY720 has a protective effect on AILI. AILI was induced using intraperitoneal injection of 300 mg/kg APAP in male C57BL/6J mice. Following APAP challenge, the mice were administered 5 mg/kg FTY720 for 30 min. Protein expression levels were measured using western blot analysis. Cell viability was examined using Cell Counting Kit‑8 assays. mRNA levels were measured using reverse transcription‑quantitative PCR. Inflammation levels were evaluated using immunohistochemistry. Cell death and reactive oxygen species levels were examined using immunofluorescence. Furthermore, laser scanning intravital microscopy was used to directly observe immune cell recruitment. APAP treatment increased the serum levels of alanine transaminase and aspartate transaminase at the 6‑ and 12‑h time‑points, suggesting liver tissue damage. However, FTY720 attenuated the liver injury induced by APAP by reducing the recruitment of immune cells and the release of pro‑inflammatory cytokines and chemokines. FTY720 activated JAK2/STAT3 signaling and regulated the expression of BAX, BCL‑2 and p65 to inhibit apoptosis and inflammation. In addition, compared with APAP treatment, the viability of primary hepatocytes treated with APAP and FTY720 was increased. Inhibition of JAK2/STAT3 signaling attenuated the protective, antioxidant effects of FTY720. In conclusion, FTY720 reduced liver injury by regulating the JAK2/STAT3 signaling pathway. This compound was capable of inhibiting oxidative stress to reduce hepatocyte death and the infiltration of neutrophils in the liver.

Dataset Information

Inhibition of Stat3 Signaling Pathway by Natural Product Pectolinarigenin Attenuates Breast Cancer Metastasis.

Publications

Inhibition of Stat3 Signaling Pathway by Natural Product Pectolinarigenin Attenuates Breast Cancer Metastasis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets