ReferenceID 2000

Gossypol induces apoptosis of multiple myeloma cells through the JUN-JNK pathway

Am J Cancer Res

Multiple myeloma (MM) is one of the most common hematologic neoplastic diseases. Gossypol was once used as a male contraceptive but is considered a novel antitumor agent. This study aimed to reveal the gossypol-induced a

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Reference Id
2000
Evidence Id
18590
Core Evidence Id
18590
Source Reference Id
4018
Herb2 Reference Id
HBREF004815
Subject Paper Key
HBIN028351_32266096
Pubmed Id
32266096
Doi
Paper Title
Gossypol induces apoptosis of multiple myeloma cells through the JUN-JNK pathway
Paper Abstract
Multiple myeloma (MM) is one of the most common hematologic neoplastic diseases. Gossypol was once used as a male contraceptive but is considered a novel antitumor agent. This study aimed to reveal the gossypol-induced apoptosis mechanism and its hub genes. Gossypol-induced MM cell apoptosis is concentration- and time-dependent. Of a total of 532 differentially expressed genes, 273 genes were upregulated and 259 genes were downregulated in gossypol-treated MM cells. Through KEGG and WGCNA analyses, the apoptosis-associated module was identified, and JUN was identified as the hub gene. The expression of the JUN protein product c-Jun was downregulated in MM cell lines compared to that in normal plasma cells. High-risk MM patients had a lower expression of JUN. High-expression JUN group patients had a lower risk of death. JUN overexpression in MM cells induced potent cell death and growth inhibition by a caspase-dependent apoptotic mechanism. DR5 is one of the upstream receptors of the JNK pathway, and shRNA knockdown of DR5 can partially reverse gossypol-induced apoptosis. A total of 1017 genes were coexpressed with JUN in MM patients. These genes are mainly involved in other JNK-associated signaling pathways, such as the IL6, EGF and PDGF signaling pathways. In conclusion, JUN is identified as the hub gene in gossypol-induced apoptosis, and gossypol can activate caspase-dependent apoptosis through the JNK pathway by targeting c-Jun and other JNK-associated pathways. DR5 and IL6 are also involved in this mechanism.
Journal
Am J Cancer Res
Publish Year
2020
Experiment Subject
patient; gossypol-treated mm cells; mm cell lines; mm cells
Experiment Type
Cell Experiment
Phenotype Related
Multiple Myeloma; Hematologic Neoplastic Diseases
Paper Title Cn
Paper Title En
Gossypol induces apoptosis of multiple myeloma cells through the JUN-JNK pathway
Bilingual Status
semi_complete