Valrubicin is a second generation
anthracycline characterized by an excellent safety profile presenting no skin toxicity or
necrosis upon contact. In its current liquid formulation (
Valstar; Indevus
Pharmaceuticals, Lexington, MA), it is approved solely for the treatment of
bladder cancer. Recently,
valrubicin was incorporated in a cream formulation rendering this
drug available for topical application. The
cytostatic property of
valrubicin can, thus, be employed for treating hyperproliferative
skin diseases as was recently described for
psoriasis. In the present study, the effect of topical application of
valrubicin was investigated in skin
tumor development; we hypothesized that
valrubicin may be employed in treating
actinic keratosis, a hyperproliferative skin condition that may transform into
malignancy. A two-stage chemical mouse skin
carcinogenesis model that represents the multistage etiology of human
skin cancer-from developing
papillomas to
squamous cell carcinoma (SCC) was used. Moreover, two human skin SCC cell lines: DJM-1 and HSC-1 were cultured, to further investigate the effect of
valrubicin in vitro. Cell viability was assessed by
adenosine triphosphate presence, proliferation as proliferative cell
nuclear antigen expression and apoptosis as
cytokeratin 18 cleavage,
caspase activation,
poly-adenosine diphosphate-ribose-polymerase cleavage and bax and bcl-2 regulation.
Valrubicin significantly inhibited
tumor formation in the mouse skin
carcinogenesis model and significantly decreased cell viability of the cultured human skin SCC cells. In both mouse skin and SCC cells, proliferation was significantly decreased. Apoptosis was significantly increased in SCC cells but unchanged in the treated mouse skin at study completion. This study demonstrated that topical application of
valrubicin has a beneficial effect in treating developing skin
tumors.