Takita Sumter, Ph.D.
College of Arts and Sciences
Chemistry, Physics and Geology
The architectural chromatin binding proteins High Mobility Group A1 (HMGA1) are proteins expressed at high levels in malignant cancers and induce neoplastic transformation. The protein is increased as the last step of the Wnt/B-catenin/TCF-4 pathway and mediates drug resistance, therefore correlating with a poor patient prognosis. HMGA1-mediated chemoresistance results from a self-protective process called cellular senescence. Analogs of the antioxidant, curcumin, when used in combination with traditional chemotherapeutic agents, are useful treatment options for drug resistant tumors. This study had two specific aims. The first being to investigate how colon cancer cells HCT116 respond to treatment with EF24. The second aim was to evaluate how hmga1 expression changed as a result of treatment with EF24. Our preliminary findings showed that cell viability decreased after 24-hour treatment with low-dose EF24, as indicated by an MTS assay, with notable discrepancies between cells that underwent a pulsed treatment regimen versus those that underwent continuous treatment. Furthermore, we demonstrated that cells exhibited fragmented DNA when treated with low-dose EF24, which is characteristic of apoptotic cells. At higher, pulsed doses, senescence activity increased, indicating the induction of a senescence pathway. Lastly, gene expression studies indicated that hmga1 was significantly down regulated in cells treated with continuous, low-dose EF24. Further investigation of this pathway could lead to decreased toxicity and increased viability of combination cancer therapies.
Diaz, Madeline and Sumter, Takita
"Evaluation of the Potential HMGA1-EF24 Nexus in Human Colon Cancer,"
The Winthrop McNair Research Bulletin: Vol. 3
, Article 4.
Available at: http://digitalcommons.winthrop.edu/wmrb/vol3/iss1/4