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microRNA let-7c is essential for the anisomycin-elicited apoptosis in Jurkat T cells by linking JNK1/2 to AP-1/STAT1/STAT3 signaling.

Zhou Z, Lu X, Wang J, Xiao J, Liu J, Xing F - Sci Rep (2016)

Bottom Line: 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 deficiency reduced the AP-1, STAT1 and Bim activities, and enhanced the STAT3 and Bcl-xL, alleviating the anisomycin-induced apoptosis.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Tissue Transplantation and Immunology, Department of Immunobiology, Jinan University, Guangzhou 510632, China.

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.

No MeSH data available.


Related in: MedlinePlus

Low dose anisomycin strongly induces the apoptosis in Jurkat T cells.Two hours after pre-incubated with or without 10 μM SP600125 (SP) or 20 μM PD98059 (PD), Jurkat T cells were treated with the indicated concentrations of anisomycin (Ani) for 6 h or 24 h or with 40 ng/ml of anisomycin for the indicated time periods. (A,B) DNA fragmentation in the treated cells was analyzed by 1% agarose gel electrophoresis. (C–E) Apoptotic proportion in the treated cells was assayed by flow cytometry using annexin-V/PI double staining. The results show the typical experiment, which has been repeated three times.
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f1: Low dose anisomycin strongly induces the apoptosis in Jurkat T cells.Two hours after pre-incubated with or without 10 μM SP600125 (SP) or 20 μM PD98059 (PD), Jurkat T cells were treated with the indicated concentrations of anisomycin (Ani) for 6 h or 24 h or with 40 ng/ml of anisomycin for the indicated time periods. (A,B) DNA fragmentation in the treated cells was analyzed by 1% agarose gel electrophoresis. (C–E) Apoptotic proportion in the treated cells was assayed by flow cytometry using annexin-V/PI double staining. The results show the typical experiment, which has been repeated three times.

Mentions: As shown in Fig. 1A,B, DNA fragmentations in the cells were gradually increased with the extended exposure time of anisomycin (Ani) or the enhancing concentrations of anisomycin, which was rescued by SP600125 (SP) (Anthra[1,9-cd]pyrazol-6-(2H)-one), an inhibitor for not only JNK, but also MKK4 and MKK7 that are upstream kinases of the JNK. Consistent with the trend of DNA fragmentation alteration, the percentages of the anisomycin-induced apoptotic cells were also increased in a time- or dose-dependent manner (Fig. 1C–E). 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 JNK signaling.


microRNA let-7c is essential for the anisomycin-elicited apoptosis in Jurkat T cells by linking JNK1/2 to AP-1/STAT1/STAT3 signaling.

Zhou Z, Lu X, Wang J, Xiao J, Liu J, Xing F - Sci Rep (2016)

Low dose anisomycin strongly induces the apoptosis in Jurkat T cells.Two hours after pre-incubated with or without 10 μM SP600125 (SP) or 20 μM PD98059 (PD), Jurkat T cells were treated with the indicated concentrations of anisomycin (Ani) for 6 h or 24 h or with 40 ng/ml of anisomycin for the indicated time periods. (A,B) DNA fragmentation in the treated cells was analyzed by 1% agarose gel electrophoresis. (C–E) Apoptotic proportion in the treated cells was assayed by flow cytometry using annexin-V/PI double staining. The results show the typical experiment, which has been repeated three times.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834478&req=5

f1: Low dose anisomycin strongly induces the apoptosis in Jurkat T cells.Two hours after pre-incubated with or without 10 μM SP600125 (SP) or 20 μM PD98059 (PD), Jurkat T cells were treated with the indicated concentrations of anisomycin (Ani) for 6 h or 24 h or with 40 ng/ml of anisomycin for the indicated time periods. (A,B) DNA fragmentation in the treated cells was analyzed by 1% agarose gel electrophoresis. (C–E) Apoptotic proportion in the treated cells was assayed by flow cytometry using annexin-V/PI double staining. The results show the typical experiment, which has been repeated three times.
Mentions: As shown in Fig. 1A,B, DNA fragmentations in the cells were gradually increased with the extended exposure time of anisomycin (Ani) or the enhancing concentrations of anisomycin, which was rescued by SP600125 (SP) (Anthra[1,9-cd]pyrazol-6-(2H)-one), an inhibitor for not only JNK, but also MKK4 and MKK7 that are upstream kinases of the JNK. Consistent with the trend of DNA fragmentation alteration, the percentages of the anisomycin-induced apoptotic cells were also increased in a time- or dose-dependent manner (Fig. 1C–E). 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 JNK signaling.

Bottom Line: 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 deficiency reduced the AP-1, STAT1 and Bim activities, and enhanced the STAT3 and Bcl-xL, alleviating the anisomycin-induced apoptosis.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Tissue Transplantation and Immunology, Department of Immunobiology, Jinan University, Guangzhou 510632, China.

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.

No MeSH data available.


Related in: MedlinePlus