Hyaluronidase activation of c-Jun N-terminal kinase is necessary for protection of L929 fibrosarcoma cells from staurosporine-mediated cell death.

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Chang NS

Hyaluronidase activation of c-Jun N-terminal kinase is necessary for protection of L929 fibrosarcoma cells from staurosporine-mediated cell death.

Biochem Biophys Res Commun. 2001 May 4;283(2):278-86.

PubMed ID

11327694 [ View in PubMed

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Abstract

Hyaluronidase counteracts the growth inhibitory function of transforming growth factor beta (TGF-beta), whereas secretion of autocrine TGF-beta and hyaluronidase is necessary for progression and metastasis of various cancers. Whether hyaluronidase and TGF-beta1 induce resistance to staurosporine in L929 fibrosarcoma cells was investigated. When pretreated with TGF-beta1 for 1-2 h, L929 cells resisted staurosporine apoptosis. In contrast, without pretreatment, hyaluronidase protected L929 cells fromstaurosporine apoptosis. Hyaluronidase rapidly activated p42/44 MAPK (or ERK) in L929 cells and TGF-beta1 retarded the activation. Nonetheless, TGF-beta1 synergistically increased hyaluronidase-mediated inhibition of staurosporine apoptosis. Hyaluronidase rapidly activated c-Jun N-terminal kinase (JNK1 and JNK2) in L929 cells in 20 min. Dominant negative JNK1, JNK2, and JNK3 abolished the hyaluronidase inhibition of staurosporine apoptosis, but not the TGF-beta1 protective effect. Unlike the resistance to staurosporine, pretreatment of L929 cells with hyaluronidase is necessary to generate resistance to other anticancer drugs, including doxorubicin, daunorubicin, actinomycin D, and camptothecin, and the induced resistance was also blocked by dominant-negative JNKs. Together, hyaluronidase-mediated JNK activation is necessary to generate resistance to various anticancer drugs in L929 cells.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Hyaluronidase	Transforming growth factor beta-1	Protein	Humans	Unknown	Inhibitor	Details
Hyaluronidase (human recombinant)	Transforming growth factor beta-1	Protein	Humans	Unknown	Inhibitor	Details
Hyaluronidase (ovine)	Transforming growth factor beta-1	Protein	Humans	Unknown	Inhibitor	Details