Abstract
Anisomycin, an antibiotic produced by Streptomyces griseolus, strongly induces apoptosis in various tumor cells in vitro, superior dramatically to adriamycin. The present study aims to elucidate its detailed mechanistic process. The results showed that anisomycin sufficiently promoted the apoptosis in human leukemic Jurkat T cells at a quite low dose. microRNA let-7c (let-7c) contributed to the anisomycin-induced apoptosis, which could be abrogated by the inactivation of JNK signaling. The let-7c over-expression and the addition of its mimics facilitated the activation of AP-1, STAT1 and Bim by linking JNK1/2 to AP-1/STAT1, but rather inhibited the activation of STAT3 and Bcl-xL by connecting JNK1/2 to STAT3, followed by the augmented apoptosis in the cells. The let-7c deficiency reduced the AP-1, STAT1 and Bim activities, and enhanced the STAT3 and Bcl-xL, alleviating the anisomycin-induced apoptosis. The knockdown of the bim gene repressed the anisomycin-boosted apoptosis through the attenuation of the active Bak and Bax. The findings indicate for the first time that miR let-7c is essential for the anisomycin-triggered apoptosis by linking JNK1/2 to AP-1/STAT1/STAT3/Bim/Bcl-xL/Bax/Bak signaling. This provides a novel insight into the mechanism by which anisomycin leads to the tumor cell apoptosis, potentially laying the foundations for its development and clinical application.
Highlights
The induction of apoptosis in cancer cells is one of key strategies for cancer therapy[1,2]
The percentage of 40 ng/ml anisomycin-induced apoptotic cells reached 47.9% at 24 h after the treatment. These results demonstrate that anisomycin strongly induces the apoptosis in Jurkat T cells through the Jun N-terminal kinases (JNKs) signaling
Our studies indicate that the activation of JNK1/2 is more predominant than that of p38 in the anisomycin-induced apoptosis
Summary
The induction of apoptosis in cancer cells is one of key strategies for cancer therapy[1,2]. Several studies have shown that the anisomycin induces the apoptosis in cancer cells by activating the c-Jun N-terminal kinases (JNKs) or/and p38 MAPK11–15. MicroRNAs are small (about 18–24 nucleotides) noncoding RNAs that negatively regulate the gene expression post-transcriptionally by binding to specific mRNA targets and promoting their degradation and/or translational inhibition[23]. Due to their abundant presence, there is mounting evidence suggesting that miRNAs play pivotal roles in a wide spectrum of the biological processes, including the apoptosis[24]. This study is to elucidate a detailed mechanistic process of the anisomycin-induced cell apoptosis
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
