Blood Thinner “Warfarin” Acts as Anti-cancer Agent: Study

Columbia University researchers have made a surprising discovery regarding the potential anti-cancer properties of warfarin, a commonly used blood thinner. This revelation comes from a study conducted on human cells and mice, revealing that warfarin possesses the ability to impede tumor growth by preventing interference with a cellular self-destruct mechanism triggered in response to mutations or irregularities. 

Wei Gu, Ph.D., the Abraham and Mildred Goldstein Professor of Pathology & Cell Biology at Columbia University Vangelos College of Physicians and Surgeons, and the leader of the study, emphasizes that these findings suggest warfarin, which is already approved by the FDA (Food and Drug Administration) for other purposes, could be repurposed to treat various forms of cancer, including pancreatic cancer. 

Published on July 18 in the journal Cell Metabolism under the title “Regulation of VKORC1L1 is critical for p53-mediated tumor suppression through vitamin K metabolism,” the study involved the contributions of first authors Xin Yang, Ph.D., and Zhe Wang, Ph.D., who are postdoctoral researcher scientists. 

The research took an unexpected turn during investigations into the molecular processes governing ferroptosis, a recently identified cell death mechanism that hinges on iron. This avenue of inquiry was led by Brent Stockwell, Ph.D., an associate professor in the Department of Biological Sciences and Chemistry at Columbia. Ferroptosis is of great interest in cancer research due to its potential to eliminate cancer cells that are resistant to current treatments. 

In their pursuit of understanding ferroptosis regulation, Gu, Stockwell, and their team conducted genetic screenings on human melanoma cells to pinpoint genes influencing ferroptosis. Among the genes identified, one novel candidate stood out: VKORC1L1. 

Further experimentation demonstrated that VKORC1L1 acts as a potent inhibitor of ferroptosis, and its depletion sensitizes cells to ferroptosis cell death. Moreover, clinical implications surfaced as an analysis of human cancer data revealed that patients with lower VKORC1L1 activity exhibited longer survival rates compared to those with higher levels. 

Warfarin, an FDA-approved drug primarily used as a blood thinner, emerged as a potential candidate due to its known role as a VKORC1L1 inhibitor. The researchers explored its potential as an anti-cancer agent and found that warfarin, by reducing VKORC1L1 activity, heightened the sensitivity of human pancreatic cancer cells to ferroptosis. Notably, warfarin also suppressed tumor growth in a mouse model of pancreatic cancer. 

Previous studies had already hinted at the potential anti-cancer effects of warfarin. Cancer patients, who face an elevated risk of blood clots, often receive anticoagulants like warfarin. Recent observations have indicated that patients with pancreatic, gastric, and colorectal cancers who were administered warfarin survived notably longer than those on other anticoagulants. 

Given warfarin’s established clinical usage in cancer patients, the researchers believe it holds promise as an anti-cancer drug, especially for tumors expressing elevated levels of VKORC1L1. Gu expresses the belief that this potential extends beyond pancreatic and gastric cancers to encompass a range of cancer types. The study also revealed that VKORC1L1 is a direct target of p53, a well-known tumor suppressor gene frequently mutated in various cancers. 

Columbia University’s research has unveiled the intriguing possibility that warfarin, a widely used blood thinner, possesses potent anti-cancer properties. The study demonstrates that warfarin can halt tumor growth by impeding cellular interference with a self-destruct mechanism triggered by mutations. This discovery presents the prospect of repurposing warfarin for cancer treatment, offering hope for a variety of cancer types, including pancreatic cancer.

The study’s findings shed light on the molecular underpinnings of ferroptosis, a recently identified cell death mechanism dependent on iron. Importantly, warfarin’s established clinical usage in cancer patients lends further credibility to its potential as an anti-cancer agent. By uncovering the intricate interplay between warfarin, VKORC1L1, and ferroptosis, this research brings us closer to innovative and potentially more effective cancer therapies.