Arsenic induces apoptosis through a c-Jun NH2-terminal kinase- dependent, p53-independent pathway

Chuanshu Huang, Wei-Ya Ma, Jingxia Li, Zigang Dong

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184 Scopus citations

Abstract

Arsenic has been used as an effective chemotherapy agent for some human cancers, such as acute promyelocytic leukemia. In this study, we found that arsenic induces activation of c-Jun NH2-terminal kinases (JNKs) at a similar dose range for induction of apoptosis in JB6 cells. In addition, we found that arsenic did not induce p53-dependent transactivation. Similarly, there was no difference in apoptosis induction between cells with p53 +/+ or p53 - /-. In contrast, arsenic-induced apoptosis was almost totally blocked by expression of a dominant-negative mutant of JNK1. These results suggest that the activation of JNKs is involved in arsenic-induced apoptosis of JB6 cells. Taken together with previous findings that p53 mutations are involved in ~50% of all human cancers and nearly all chemotherapeutic agents kill cancer cells mainly by apoptotic induction, we suggest that arsenic may be a useful agent for the treatment of cancers with p53 mutation.

Original languageEnglish (US)
Pages (from-to)3053-3058
Number of pages6
JournalCancer Research
Volume59
Issue number13
StatePublished - Jul 1 1999

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