W‐7, a calmodulin inhibitor, potentiates dacarbazine cytotoxicity in human neoplastic cells

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Abstract
Dacarbazine induces damage in replicative DNA, with a maximum level at 24 hr after treatment. Repair of these lesions does not occur when cells are post‐treated with the calmodulin inhibitor W‐7. In parallel cell cytotoxicity increases. The augmentation effect of W‐7 is prevented by simultaneous incubation of cells with high levels of calmodulin and does not occur in cells pre‐treated with aphidicolin (to stop DNA synthesis). Furthermore, W‐5, an analogue of W‐7 with a less inhibitory effect on calmodulin, does not interfere with DNA repair. The results show that calmodulin and/or calmodulin‐regulated proteins are involved in the repair process of dacarbazine‐induced DNA lesions.
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