Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pectolinarigenin (PEC), a natural flavonoid present in Cirsium chanroenicum and in some species of Citrus fruits, has various pharmacological benefits such as anti-inflammatory and anti-cancer activities. In the present study, we investigated the anti-cancer mechanism of PEC induced cell death caused by autophagy and apoptosis in AGS and MKN28 human gastric cancer cells. The PEC treatment significantly inhibited the AGS and MKN28 cell growth in a dose-dependent manner. Further, PEC significantly elevated sub-G1 phase in AGS cells and G2/M phase cell cycle arrest in both AGS and MKN28 cells. Apoptosis was confirmed by Annexin V and Hoechst 33342 fluorescent staining. Moreover, Immunoblotting results revealed that PEC treatment down-regulated the inhibitor of apoptosis protein (IAP) family protein XIAP that leads to the activation of caspase-3 thereby cleavage of PARP (poly-ADP-ribose polymerase) in both AGS and MKN28 cells in a dose-dependent manner. The autophagy-inducing effect was indicated by the increased formation of acidic vesicular organelles (AVOs) and increased protein levels of LC3-II conversion in both AGS and MKN28 cells. PEC shows the down regulation of PI3K/AKT/mTOR pathway which is a major regulator of autophagic and apoptotic cell death in cancer cells that leads to the down-regulation of p-4EBP1, p-p70S6K, and p-eIF4E in PEC treated cells when compared with the untreated cells. In conclusion, PEC treatment might have anti-cancer effect by down-regulation of PI3K/AKT/mTOR pathway leading to G2/M phase cell cycle arrest, autophagic and apoptotic cell death in human gastric cancer cells. Further studies of PEC treatment can support to develop as a potential alternative therapeutic agent for human gastric carcinoma.
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PMID:Pectolinarigenin Induced Cell Cycle Arrest, Autophagy, and Apoptosis in Gastric Cancer Cell via PI3K/AKT/mTOR Signaling Pathway. 3009 5

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.
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PMID:Inhibition of Stat3 Signaling Pathway by Natural Product Pectolinarigenin Attenuates Breast Cancer Metastasis. 3164 48