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 |
Externí odkaz: |