Isolinderalactone Induces Cell Death via Mitochondrial Superoxide- and STAT3-Mediated Pathways in Human Ovarian Cancer Cells
| Autor: | Sang Hoon Joo, Shakya Rajina, Seo-Yeon Lee, Joon-Seok Choi, Kyung-Soo Chun, Jung-Hyun Shim, Woo Jean Kim, Hwa Kyoung Shin |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
STAT3 Transcription Factor
Programmed cell death Cell SOD2 mitochondrial superoxide Antineoplastic Agents Catalysis Article Inorganic Chemistry Superoxide dismutase lcsh:Chemistry Downregulation and upregulation Superoxides Cell Line Tumor Survivin medicine Humans Physical and Theoretical Chemistry STAT3 Molecular Biology lcsh:QH301-705.5 Spectroscopy Janus Kinases Ovarian Neoplasms biology Cell Death Activator (genetics) Chemistry Superoxide Dismutase Organic Chemistry Anti-Inflammatory Agents Non-Steroidal janus kinase General Medicine Computer Science Applications Mitochondria isolinderalactone medicine.anatomical_structure ovarian cancer lcsh:Biology (General) lcsh:QD1-999 biology.protein Cancer research signal transducer and activator of transcription 3 Female Sesquiterpenes |
| Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 20 International Journal of Molecular Sciences, Vol 21, Iss 7530, p 7530 (2020) |
| ISSN: | 1422-0067 |
| Popis: | The mortality rate of ovarian cancer (OC) worldwide increases with age. OC is an often fatal cancer with a curative rate of only 20&ndash 30%, as symptoms often appear after disease progression. Studies have reported that isolinderalactone (ILL), a furanosesquiterpene derivative extracted from the dried root of Lindera aggregata, can inhibit several cancer cell lines&rsquo growth. However, the molecular mechanisms underlying ILL activities in human OC cells remain unexplored. This study investigated the antitumor activities of ILL in human OC cells by inducing mitochondrial superoxide (mtSO) and JAK-signal transducer and activator of transcription 3 (STAT3)-dependent cell death. ILL caused cell death in SKOV-3 and OVCAR-3 cells and increased the cell proportion in the subG1 phase. Additionally, ILL significantly induced mtSO production and reduced ROS production. Moreover, ILL downregulated mitochondrial membrane potential and the expression levels of anti-apoptotic Bcl-2 family proteins and superoxide dismutase (SOD)2. Results showed that ILL decreased phosphorylation of serine 727 and tyrosine 705 of STAT3 and expression of survivin, a STAT3-regulated gene. Furthermore, ILL-induced cell death was reversed by pretreatment of Mito-TEMPO, a mitochondria-specific antioxidant. These results suggest that ILL induces cell death by upregulation of mtSO, downregulation of mitochondrial SOD2, and inactivation of the STAT3-mediated pathway. |
| Databáze: | OpenAIRE |
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