Topical application of gentian violet (GV) kills cutaneous T-cell lymphoma (CTCL) cells, according to findings recently published in JAMA Dermatology.
CTCL is characterized by resistance to apoptosis. Researchers used in vitro and ex vivo models to examine the influence of GV on the activation of extrinsic pathway apoptosis that involves the Fas and tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) death receptors and levels of nuclear factor (NF)–κB. These components are typically overexpressed in advanced-stage CTCL and play an important role in tumor cell proliferation.
Using a combination of enzyme-linked immunosorbent assays, flow cytometry, and immunoblotting, researchers analyzed 1710 compounds through high-throughput small molecule screening and observed their interactions with CTCL cells. The study found that GV showed promising results as a killer of CTCL cells by inducing high levels of cleaved caspase 8. Furthermore, apoptosis was also induced by GV (1 μmol/L) among five of the CTCL cell lines examined. The results were higher in ex vivo experiments, where 75% to 90% of cells showed apoptosis in Sézary syndrome (SS) blood samples.
Other results showed that GV augments and diminishes CTCL proliferative drivers, such as NF-κB components, and enhances the expression of IκB. These important findings show that GV can be a better inducer of the extrinsic and intrinsic apoptotic pathways than compounds such as nitrogen mustard.
The study has some limitations. Only CTCL cell lines and blood samples from SS patients were used for analysis. These cells come from advanced forms of CTCL and do not necessarily predict the behavior of early CTCL cells when reacting to GV.
The authors concluded that GV is an inexpensive and readily available compound and these preclinical data suggest that GV might be an effective topical agent for early-stage CTCL. These findings justify further examination through clinical studies of the effects of GV on early-stage CTCL.
Wu J, Wood GS. Analysis of the effect of gentian violet on apoptosis and proliferation in cutaneous T-cell lymphoma in an in vitro study [published online August 29, 2018]. JAMA Dermatol. doi: 10.1001/jamadermatol.2018.2756