Jianqiang Wu, MD, PhD
Gary S. Wood, MD
As reported in JAMA Dermatology, Jianqiang Wu, MD, PhD, and Gary S. Wood, MD, found that the widely available nonprescription topical antimicrobial agent gentian violet has potent activity against cutaneous T-cell lymphoma (CTCL) in studies in vitro and ex vivo. The study involved high-throughput small molecule screening of 1,710 compounds to detect cleaved caspase 8 induced in CTCL, indicative of activation of extrinsic and intrinsic apoptotic pathways.
Among the compounds screened, nitrogen mustard was found to be among the highest inducers of cleaved caspase 8 in CTCL cells. However, gentian violet was found to induce similar levels of cleaved caspase 8 and induce greater levels of total apoptosis; the agent induced 4 to 6 times greater apoptosis in CTCL lines than in normal keratinocytes, indicating a potentially favorable topical toxicity profile.
Activity of Gentian Violet
Further characterization of gentian violet showed that it upregulated death receptors 4 and 5, tumor necrosis factor (TNF)-related apoptosis-inducing ligand, and Fas ligand but not Fas receptors, TNF receptors, or TNF-α ligand—activities consistent with the induction of extrinsic apoptosis via the Fas and TNF-related apoptosis-inducing ligand pathways. The agent also increased phosphorylation of phospholipase C-γ1, Ca2+ influx, and reactive oxygen species, activities suggesting that Fas ligand upregulation involved central components of the activation-induced cell death pathway.
In ex vivo studies, 1 μmol/L of gentian violet induced up to 90% CTCL apoptosis in Sézary blood cells. The agent was also found to reduce expression of antiapoptotic myeloid cell leukemia 1 and proproliferative nuclear factor–κB components and increase inhibitory κB levels—activities that were associated with cell-cycle arrest and reduction of CTCL tumor cell proliferation. The combination of gentian violet and methotrexate resulted in increased CTCL killing.
The investigators concluded, “This study found that [gentian violet] attacked tumor viability and growth in CTCL. Although purple at neutral pH, [gentian violet] can be rendered colorless by altering its pH. These preclinical findings may help to broaden knowledge of the antineoplastic features of [gentian violet] and provide a rationale for clinical studies of its use as a novel, inexpensive, topical therapy for CTCL that is available worldwide."