You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: ["HealthCareActivity", "InjuryOrPoisoning", "BodySubstance", "IntellectualProduct", "AnatomicalStructure", "SpatialConcept", "Chemical", "Bacterium", "MedicalDevice", "Organization", "BiomedicalOccupationOrDiscipline", "Finding", "BiologicFunction", "Virus", "ResearchActivity", "ClinicalAttribute", "PopulationGroup", "Eukaryote", "BodySystem", "Food", "ProfessionalOrOccupationalGroup"].

Please return the output as a JSON object of the format: {"Virus": ["HIV", ...], "Bacterium": ["MRSA", ...], "AnatomicalStructure": ["Lung", ...], "BodySystem": ["CNS", ...], "BodySubstance": ["Serum", ...], "Finding": ["Headache", ...], "InjuryOrPoisoning": ["Fracture", ...], "BiologicFunction": ["Death", ...], "HealthCareActivity": ["Biopsy", ...], "ResearchActivity": ["Clinical trial", ...], "MedicalDevice": ["Lenses", ...], "SpatialConcept": ["Camps", ...], "BiomedicalOccupationOrDiscipline": ["Forensic medicine", ...], "Organization": ["WHO", ...], "ProfessionalOrOccupationalGroup": ["Provider", ...], "PopulationGroup": ["Swimmers", ...], "Chemical": ["Gold", ...], "Food": ["Rice", ...], "IntellectualProduct": ["RPAM", ...], "ClinicalAttribute": ["Biomarker", ...], "Eukaryote": ["Dogs", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].

Only output the JSON object and do not include any additional text.

Abstract:

Anti-tumor activity of SL4 against breast cancer cells: induction of G2/M arrest through modulation of the MAPK -dependent p21 signaling pathway SL4, a chalcone -based compound, has been shown to retard tumor invasion and angiogenesis by suppressing HIF1 activity and to induce apoptosis by promoting ROS release. Here, we report that SL4 is able to inhibit the proliferation of different types of breast cancer cell in vitro and in vivo by inducing G2/M cell cycle arrest. Our results showed that SL4 exhibited strong anti-proliferative activity in several human breast cancer cell lines, with IC50 values lower than 1.3 μM. Further studies indicated that SL4 induced G2/M arrest in these cell lines. Mechanistically, SL4 reduces the expression of cyclin A2 and cdc25C and decreases the activity of the cdc2 / cyclin B1 complex. Notably, SL4 treatment resulted in an obvious increase in p21 mRNA and protein levels through activation of MAPK signaling pathways, but not the TGF-β pathway. SP600125 and PD98059, specific inhibitors of JNK kinase and ERK kinase, significantly blocked the SL4 - induced G2/M phase arrest and upregulation of p21. Furthermore, SL4 suppressed the growth of established breast tumors in nude mice through upregulation of p21 and downregulation of cdc25C, and displayed a good safety profile. Taken together, these findings demonstrate the potential value of SL4 as a novel multi-target anti-tumor drug candidate.
{"AnatomicalStructure": ["breast cancer cell", "cell lines", "p21", "breast cancer cells"], "Bacterium": [], "BiologicFunction": ["activation", "Anti-tumor activity", "upregulation", "downregulation", "apoptosis", "proliferation", "breast cancer", "signaling pathway", "MAPK signaling pathways", "breast tumors", "expression", "TGF-\u03b2 pathway", "G2/M phase arrest", "G2/M arrest", "angiogenesis", "G2/M cell cycle arrest", "growth"], "BiomedicalOccupationOrDiscipline": [], "BodySubstance": [], "BodySystem": [], "Chemical": ["cyclin A2", "p21", "SL4", "cdc25C", "inhibitors", "PD98059", "cdc2", "ERK kinase", "multi-target anti-tumor drug candidate", "anti-proliferative", "compound", "JNK kinase", "HIF1", "complex", "SP600125", "ROS", "cyclin B1", "chalcone", "protein", "mRNA", "MAPK"], "ClinicalAttribute": [], "Eukaryote": ["human", "nude mice"], "Finding": ["indicated", "tumor invasion", "findings"], "Food": [], "HealthCareActivity": ["treatment"], "InjuryOrPoisoning": [], "IntellectualProduct": ["report"], "MedicalDevice": [], "Organization": [], "PopulationGroup": [], "ProfessionalOrOccupationalGroup": [], "ResearchActivity": ["studies"], "SpatialConcept": ["in vivo"], "Virus": []}