The Expression and Value of Aldolase in Endometrial Cancer and the Role of Clotrimazole in Endometrial Cancer Cell Viability and Morphology.
Stuti Shroff, Dan Wang, Joshua Kesterson, Song Liu, Kunle Odunsi, Paulette Mhawech-Fauceglia. University at Buffalo, SUNY, Buffalo, NY; Roswell Park Cancer Institute, Buffalo, NY
Background: Previously, using cDNA microarray gene expression, we found that aldolaseC was among numerous genes upregulated in uterine serous carcinoma in comparison to endometrioid adenocarcinoma. Aldolase is a critical enzyme in the glycolytic pathway. Most cancer cells use this pathway for generation of ATP as a main source of their energy supply. Clotrimazole, an antifungal agent, has been proven to induce a dose-dependent detachment of aldolase from the cytoskeleton, leading to cell damage and destruction. Our aims are to evaluate the value of aldolaseC in endometrial carcinoma (EC) and to determine the impact of clotrimazole in inhibition of cell viability and alteration of cell structure in EC cell line.
Design: To accomplish the first aim, aldolaseC protein expression using immunohistochemistry analysis was performed on 350 paraffin-embedded EC tissues. Next, fresh frozen tissue from 70/350 samples were available to evaluate the aldolaseC mRNA level using Taqman RT-PCR. For the second aim, endometrial cancer cell line cell (HEC1) and colonic cancer cell line (CT26) (as a control) with and without treatment with clotrimazole were evaluated for cell viability by tryptan blue dye and for cell structure by transmission electron microscope at different times.
Results: AldolaseC protein was expressed in 78% EC cases. High aldolaseC mRNA levels were associated with low tumor grade (p=0.002), serous subtypes (p=0.006) and longer overall survival (p=0.051). Treatment of cancer cell lines with clotrimazole induced detachment of cancer cells from culture plates. Total cell death was seen 4 hrs post-treatment in CT26 and 24 hrs in HEC1. The effect of clotrimazole on HEC1 at 4 hrs manifested as small discontinuities of the cell membrane, swollen mitochondria with loss of cristae and very granular cytoplasm. At the 24 hrs time point, cell death had occurred evidenced by loss of integrity of the plasma membrane, leading to cell rupture.
Conclusions: Although preliminary, our data is the first to shed light on the value of aldolaseC in EC. We provided evidence of the effect of clotrimazole in EC cell viability and cell structure. We hope our results will open the door for future in vivo investigation and raise the option of clotrimazole as a new therapeutic agent in EC patients
Category: Gynecologic & Obstetrics
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 173, Wednesday Afternoon