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Camptothecin‐induced apoptosis is enhanced by Myc and involves PKCdelta signaling
Author(s) -
Albihn Ami,
Mo Hao,
Yang Ying,
Henriksson Marie
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22866
Subject(s) - apoptosis , camptothecin , downregulation and upregulation , cancer research , biology , caspase , signal transduction , oncogene , paclitaxel , cell culture , programmed cell death , microbiology and biotechnology , chemistry , cell cycle , chemotherapy , gene , biochemistry , genetics
The MYC oncogene is frequently deregulated in human tumors, indicative of a poor prognosis because of enhanced resistance to treatment. In such cases, the cellular sensitivity to chemotherapy could be restored by reactivation of Myc‐driven apoptosis. We have analyzed apoptosis induced by the cytotoxic agents camptothecin (CPT) and paclitaxel (PTX) using Rat1 fibroblasts with different c‐myc status and human Tet21N neuroblastoma cells with conditional MYCN expression. In these cell lines, the drug sensitivity was enhanced by Myc in line with previous reports showing that Myc sensitizes to apoptosis induction by many different apoptosis inducers. CPT‐induced apoptosis involved cleavage and activation of proapoptotic Bid and Bax, induction of mitochondrial membrane depolarization, activation of caspase‐9 and caspase‐3, protein kinase c delta (PKCδ) signaling and upregulation of p53. We also observed reduced transcriptional activity by Myc and other transcription factors in response to CPT. In contrast, the manner by which Myc potentiates the apoptosis induced by PTX differs from that of CPT and remains to be explored. In summary, our findings revealed that activation of PKCδ in response to CPT treatment requires Myc and is important in CPT‐mediated apoptosis signaling. © 2007 Wiley‐Liss, Inc.