Flavonoids identified from Korean Scutellaria baicalensis induce apoptosis by ROS generation and caspase activation on human fibrosarcoma cells.
The effects of flavonoids from Korean Scutellaria baicalensis on fibrosarcoma HT1080 cells and their underlying molecular mechanism were investigated in this study. Flavonoids affected HT1080 cell proliferation by interrupting cell cycle progress, obviously augmenting the proportion of sub-G1 and diminishing that of G1 phase, and undergoing apoptosis at the tested dosage (100-400 μg/mL). In addition, the mediated apoptosis was mainly caused by total reactive oxygen species (ROS) generation and by up-regulating the ratio of Bax/Bcl-xL, triggering caspase cascades (caspase-3, -9 and -8), and inactivating PARP, dose-dependently. The proteomics results showed that AP-4, ARID 5B, HNRNP K, PLOG, Prdx6, and myosin-1, associated with cell growth, differentiation and development, and overexpressed in gastric cancer, colorectal cancer, pancreatic cancer, etc., were statistically down-regulated after the flavonoids treatment. Taken together, our data demonstrated that flavonoids from Korean S. baicalensis induced apoptosis in HT1080 cells, which involved a hierarchy of cellular pathways and multiple signal proteins, and might be a potential anticancer therapeutic agent.
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu 214063, China.
Jue
J
Zhang
Hyeon-Soo
HS
Park
Jin-A
JA
Kim
Gyeong-Eun
GE
Hong
Arulkumar
A
Nagappan
Kwang-Il
KI
Park
Gon-Sup
GS
Kim
D017209:Apoptosis / Q000187:drug effects*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005354:Fibrosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005419:Flavonoids / Q000302:isolation & purification* / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000378:metabolism; D006801:Humans; D007723:Korea; D010936:Plant Extracts / Q000737:chemistry*; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species / Q000009:adverse effects* / Q000378:metabolism*; D031364:Scutellaria baicalensis / Q000737:chemistry*; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
C503805:ARID5B protein, human; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D005419:Flavonoids; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D010936:Plant Extracts; C404766:REPIN1 protein, human; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; C499814:Scutellaria baicalensis extract; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D020169:Caspases