Hemistepsin a Induces Apoptosis of Hepatocellular Carcinoma Cells by Downregulating STAT3

Autor: Sang Mi Park, Sang Chan Kim, Sae-Kwang Ku, Sung Hwan Ki, Il Je Cho, Jae Kwang Kim, Eun Ok Kim
Rok vydání: 2021
Předmět:
0301 basic medicine
Apoptosis
Hemistepta lyrata (Bunge) Bunge
medicine.disease_cause
chemistry.chemical_compound
Lactones
0302 clinical medicine
Annexin
Genes
Reporter

hepatocellular carcinoma (HCC) cells
oxidative stress
signal transducer and activator of transcription 3 (STAT3)
Biology (General)
Cytotoxicity
STAT3
Spectroscopy
chemistry.chemical_classification
biology
Chemistry
Liver Neoplasms
General Medicine
Sorafenib
Recombinant Proteins
Computer Science Applications
Neoplasm Proteins
Gene Expression Regulation
Neoplastic

030220 oncology & carcinogenesis
embryonic structures
Sesquiterpenes
STAT3 Transcription Factor
Transcriptional Activation
Carcinoma
Hepatocellular

QH301-705.5
Down-Regulation
Catalysis
Article
Inorganic Chemistry
hemistepsin A (HsA)
03 medical and health sciences
Cell Line
Tumor

medicine
Humans
Viability assay
Physical and Theoretical Chemistry
QD1-999
Molecular Biology
Protein Kinase Inhibitors
Reactive oxygen species
Organic Chemistry
Glutathione
Molecular biology
Antineoplastic Agents
Phytogenic

body regions
030104 developmental biology
biology.protein
Drug Screening Assays
Antitumor

Oxidative stress
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 9
International Journal of Molecular Sciences, Vol 22, Iss 4743, p 4743 (2021)
ISSN: 1422-0067
Popis: Hemistepta lyrata (Bunge) Bunge is a biennial medicinal plant possessing beneficial effects including anti-inflammation, and hemistepsin A (HsA) isolated from H. lyrata has been known as a hepatoprotective sesquiterpene lactone. In this report, we explored the cytotoxic effects of H. lyrata on hepatocellular carcinoma (HCC) cells and investigated the associated bioactive compounds and their relevant mechanisms. From the viability results of HCC cells treated with various H. lyrata extracts, HsA was identified as the major compound contributing to the H. lyrata-mediated cytotoxicity. HsA increased expression of cleaved PARP and cells with Sub-G1 phase, Annexin V binding, and TUNEL staining, which imply HsA induces apoptosis. In addition, HsA provoked oxidative stress by decreasing the reduced glutathione/oxidized glutathione ratio and accumulating reactive oxygen species and glutathione-protein adducts. Moreover, HsA inhibited the transactivation of signal transducer and activator of transcription 3 (STAT3) by its dephosphorylation at Y705 and glutathione conjugation. Stable expression of a constitutive active mutant of STAT3 prevented the reduction of cell viability by HsA. Finally, HsA enhanced the sensitivity of sorafenib-mediated cytotoxicity by exaggerating oxidative stress and Y705 dephosphorylation of STAT3. Therefore, HsA will be a promising candidate to induce apoptosis of HCC cells via downregulating STAT3 and sensitizing conventional chemotherapeutic agents.
Databáze: OpenAIRE