Cytotoxic activity of cyclosporin A and [3-keto-Bmt1]-[Val2]-cyclosporin (SDZ PSC 833) on tumour cells from patients with haematological malignancies

Abstract

Objective and method: The fluorometric microculture cytotoxic assay was employed for characterisation of the cytotoxic effect of cyclosporin A (CsA) and its non-immunosuppressive analogue SDZ PSC 833, [3-keto-Bmt¹]-[Val²]-cyclosporin (PSC) in tumour cells from patients with haematological or solid tumours.

Results: Tumour cells from patients with chronic lymphocytic leukaemia (CLL) or non-Hodgkin's lymphoma (NHL) were found to be more sensitive to both drugs than those of tumour cells from patients with acute lymphocytic leukaemia (ALL), acute myoblastic leukaemia (AML) and various solid tumours. There was a close correlation between the effects of the two drugs (correlation coefficient 0.71), but CsA was slightly more active than PSC in most diagnoses. No tumour cell sample showed sensitivity to PSC without also being sensitive to CsA. There was a moderate level of correlation between the activity pattern of CsA and doxorubicin (correlation coefficient 0.66), whereas the correlations with other cytostatics, such as vincristine, cytarabine and melphalan, were low (correlation coefficient −0.11 to 0.33).

Conclusion: The results indicate that PSC shares the direct cytotoxic properties of CsA, but is slightly less potent. Clinical testing of the cytotoxic effect of these agents in haematological malignancies seems warranted and the apparent non-cross-resistance with standard agents makes cyclosporins a potentially useful adjunct to chemotherapy in those diagnoses.