Repurposing Aspirin for Chemoresistant Breast Cancer Cells
Posted: Tuesday, December 8, 2020
An aspirin a day may keep cancer away, according to recently published research findings in the journal Science Signaling. Tanya Das, PhD, of Bose Institute, India, and colleagues suggest aspirin may be especially helpful in breast cancer treatment. Their findings showed that aspirin could inactivate molecular pumps cancer cells use to expel chemotherapy drugs.
“Our findings revealed that [cancer stem cell resistance] is driven by the inherent repression of SMAR1 expression by Oct4 and Sox2, but that the nonsteroidal anti-inflammatory drug aspirin restores both SMAR1 expression and chemosensitivity in [cancer stem cells],” wrote the authors.
The study collected cancer stem cells from invasive breast tumors to analyze the expression of the SMAR1 protein. SMAR1 acts as a DNA transcription regulator and can inhibit breast cancer tumorigenesis. The researchers found that cancer stem cells could decrease the expression of SMAR1 by using pluripotency factors Oct4 and Sox2 along with histone deacetylase HDAC1. However, when researchers overexpressed SMAR1, cancer stem cells became more sensitized to chemotherapy. This effect seems to be a result of SMAR1 enlisting HDAC2, which can block a gene for the molecular pump ABCG2.
To preserve this molecular mechanism of action, the researchers repurposed aspirin. Using tumor-bearing mice, they found that adding aspirin lowered Oct4 and Sox2 levels. Also, although aspirin alone increased SMAR1 expression, this effect was even greater when combined with doxorubicin. This combination seemed to lead to decreases in ABCG2 expression and increased sensitivity for doxorubicin.
“Aspirin might therefore be explored as a way to improve the efficacy of chemotherapy in patients with [cancer stem cells]-burdened tumors,” they concluded.
Disclosure: The authors reported no conflicts of interest.
