It is known that in empirical medicine, different anticancer drugs have different characteristic concerning specific anti-tumor or anti-leukemic efficacy and side effects on normal tissue. While solid tumors are often treated with cisplatin, treatment of leukemia is based on the use of anthracyclines and antimetabolites. Many drugs also have unique toxicities affecting normal tissues, such as the cardiotoxicity associated with the anthracyclines, the hemorrhagic cystitis associated with the

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... ophosphamide and ifosfamide. The peripheral neuropathy from vincristine, and the coagulopathy from L-asparaginase. We therefore hypothesized that the different clinical used anticancer drugs might induce apoptosis in a drug specific manner. Thus the clinical observed difference could be reflected by different activation of apoptosis signaling pathways. The molecular signaling pathways which are initiated in response to anticancer drug-induced cellular damage, and lead to the eventual apoptosis death of the cell, are largely undefined. Previous studies show the caspase family are the critical executioners of apoptosis and anticancer drug-induced apoptosis by activating two major cell-intrinsic pathways, one that begins with ligation of cell surface death receptors, such as CD95, and another that involves mitochondrial release of cytochrome c. We therefore investigated induction of apoptosis, activation of caspases and involvement of mitochondrial signaling in the well defined Jurkat human leukemic T cells by five conventional used anticancer drugs: etoposide, cytarabine, 4-hydroxy-cyclophosphamide, doxorubicin, and methotrexate, in order to identify drug specific activation of distinct apoptosis pathways. In present studies, we found some difference of apoptosis induced by these five anticancer drugs: (1) The anticancer drug-induced apoptosis appeared in different time kinetics, etoposide and cytarabine were early acting drugs, while 4-hydroxy-cyclophosphamide, doxorubicin, and methotrexate were late acting drugs. (2) Inter [...]