Author: Sean Krivitsky, Class of 2026

Figure 1. Depiction of various foods that are commonly associated with having antioxidant properties.
Prostate cancer (PC) has become a growing concern for men as its rate of incidence has been steadily increasing by more than 3% per year for the past decade. As a result, many have been searching for various treatments and interventions during PC progression to help improve overall prognosis and improve patient quality of life. One notable effort was a recent clinical trial in which selenium and vitamin E were tested in cancer prevention in tens of thousands of human male test subjects. However, contrary to what was expected and what is widely supported in major health media sources, ten years of dietary antioxidant cancer treatments led to a significant increase in incidence rates of PC tumor formation. This shocking result confused many, but, recently, research led by SBU PhD student Manojit M. Swamynathan of the Trotman lab of Cold Spring Harbor Laboratory took advantage of these curious findings by asking the following question: Can pro-oxidant treatments be used to prevent PC?

Swamynathan and his team began by treating commonly used PC mouse models using a pro-oxidant supplement called menadione sodium bisulfite (MSB), which is an organic sodium salt that is a precursor of mammalian vitamin K. The primary experimental techniques utilized were CRISPR screenings, histology staining, and whole-genome sequencing on samples isolated from treated mice. These analyses along with observations of PC mouse model survival revealed a suppression of PC progression upon treatment with MSB through a novel cell death mechanism in PC cells that is uniquely facilitated by oxidation, which the researchers termed “triaptosis”. This new cell death pathway alone is a significant finding as it helps build upon our constantly expanding understanding of mechanisms of cell death beyond the more common apoptosis and necrosis pathways. This cell death was also found to function by depletion of a specific type of phospholipid called PI(3)P, which is also found to be depleted in a separate disorder called X-linked myotubular myopathy, through the inactivation of a specific class 3 PI 3-kinase VPS34. 

Ultimately, this study helped build a desperately needed understanding of the unexpected pro-cancer effects of antioxidants and leveraged this knowledge to find a promising new treatment for not only prostate cancer but also fatal X-linked myotubular myopathy. Additionally, this work serves as a stepping stone to attempting to study the ability of other pro-oxidant substances to be used for PC prevention and treatment.

Works Cited:

[1] Manojit M. Swamynathan et al., Dietary pro-oxidant therapy by a vitamin K precursor targets PI 3-kinase VPS34 function.Science386, eadk9167(2024).DOI:10.1126/science.adk9167

[2] Image retrieved from: https://pxhere.com/en/photo/1436479