Study: Crotoxin Demonstrates Efficacy Against Melanoma with Reduced Toxicity

A new study in Frontiers in Pharmacology indicated that crotoxin (CTX), a component of snake venom, was associated with antiproliferative effects on melanoma cells.

"Melanoma, a highly aggressive skin cancer originating in melanocytes, poses a significant threat due to its metastatic potential," the authors wrote. "While progress has been made in treating melanoma with targeted therapies and immunotherapies, challenges persist. CTX, the principal toxin in Crotalus durissus terrificus snake venom, exhibits various biological activities, including anti-tumoral effects across multiple cancers. However, its clinical use is limited by toxicity. Thus, exploring alternatives to mitigate adverse effects is crucial."

The study authors compared the native form of CTX with a detoxified variant, focusing on their effects on SK-MEL-28 and MeWo melanoma cell lines. Both forms of CTX were more cytotoxic to melanoma cells than to non-tumoral cells. The detoxified form displayed reduced phospholipase activity.

Both native and detoxified CTX increased necrosis and apoptosis rates in SK-MEL-28 cells, confirmed through the activation of caspase-3 and 7 and the formation of apoptotic bodies. They also reported that CTX caused cell cycle arrest at the G2/M phase, thereby hindering melanoma cell proliferation. Both forms also were observed to suppress cell migration and invasion.

"Our collected data lead us to the conclusion that both native and detoxified forms of CTX exhibit a potent antitumor effect on human melanoma cells," the authors wrote in the study. "This effect is attributed to their cytotoxic activity, resulting in the induction of apoptosis and necrosis in melanoma cells. Furthermore, both native and detoxified CTX induce cell cycle arrest, consequently impeding the proliferation of melanoma cells. Notably, these CTX forms also inhibit the mechanisms of cell migration and invasion. Consequently, our findings provide robust evidence of CTX’s antitumor potential."

Source: Almeida T, et al. Frontiers in Pharmacology. 2024, Vol 15. Doi:10.3389/fphar.2024.1425446