Digitized Honors Theses (2002-2017)

Date of Award

5-2014

Document Type

Undergraduate Thesis

Degree Name

BS

Department

Biomedical Sciences

Faculty Mentor

Padma Thulasiraman

Abstract

An obstacle of retinoid therapy is the resistance acquired by cancer cells. Retinoic acid (RA) promotes cell cycle arrest and apoptosis through the cellular retinoic acid binding protein II/retinoic acid receptor (CRABPIIIRAR) pathway but can also enhance proliferation by activating the fatty acid binding protein/peroxisome proliferator activated receptor o (F ABPS/PPAR o) pathway. In this study, we explored how curcumin, a hydrophobic polyphenol product derived from a plant extract, exerts its anti-carcinogenic effects, by examining the role of curcumin and RA on apoptosis and cell cycle arrest in the triple negative breast cancer cell line, MDA-MB-231 cells. To evaluate curcumin's effect on apoptosis, we examined the expression level of the cleaved and active form of the apoptotic protein PARP (poly-(ADP-ribose) polymerase), and observed that curcumin did not enhance RA-induced PARP cleavage. However, treatment of MDA-MB-231 with curcumin sensitized these cells to retinoic acid mediated cell cycle arrest. We evaluated targets of the RAR pathway, the cell cycle arrest proteins BTG2 and p21, and targets of the PPARo pathway, the oncogenic and cell survival proteins PDK-1 and VEGF-A. We found that the combination of curcumin and RA increased BTG2 mRNA expression level, while having no effect on p2l expression. Moreover, combinatorial treatment with curcumin and RA.led to a decrease in PDK-1 expression, while not altering VEGF-A expression. Taken together, our data suggests that curcumin in combination with RA promotes the growth inhibitory effect of RA through cell cycle arrest by enhancing the RAR target gene, BTG2 and suppressing the PPARo target gene, PDK-1.

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