Role of SMAD signaling in drug-induced apoptosis in colon cancer

Abstract

Aberrations in SMAD signaling have been widely associated with colon cancer progression. However, their significance in modulating drug response remains unknown. In this study we investigated the response of chemotherapeutic drugs in colon cancer cells that are with (SW620 and SW480) and without aberrations (FET-1 and Caco2) in SMAD signaling. These results showed that curcumin, 5-fluorouracil and their combinations induced less cell death in SMAD signaling non-responsive cells, while the apoptosis was (>2 fold) higher in SMAD responsive cells. Furthermore, these results showed that the apoptosis in SMAD non-responsive cells was reversed and increased (~2-fold) upon ectopic expression of SMAD-4. Finally, correlation with patients undergoing chemotherapy for colon cancer showed a strong association between SMAD aberration and tumor relapse in chemotherapy. Overall, the present data showed that SMAD signaling modulates the drug responses and their signaling status should be considered while designing chemotherapy regimen for colon cancer patients.

Keywords

• Chemotherapy
• Colon cancer
• SMAD