The NSAID Sulindac Inhibits Proliferation and Induces Apoptosis in Cervical Cancer Cell Lines.
Cathy D Spillane, Christine White, Louise Kehoe, Orla Sheils, Cara M Martin, John J O'Leary. Trinity College Dublin, Ireland; Coombe Women's & Infants University Hospital, Dublin, Ireland
Background: Sulindac, a commonly used NSAID, has been investigated as a potential novel therapeutic for different forms of cancer, including colon and breast. A recent study looked at the molecular action of this drug on the HPV18 infected cervical cell line, HeLa, and demonstrated that not only could it induce apoptosis but also degrade one of the main oncoproteins, E7.
Design: This study aimed to validate the previous findings and to extend the analysis to other cervical carcinoma cell lines with differing origins, HPV status and viral DNA content. Three cervical cancer cell lines were examined, the adenocarcinoma derived HPV18 positive HeLa, the squamous cell carcinoma derived HPV16 positive SiHa and the HPV negative C33A.
Results: Sulindac had a time and dose dependent growth inhibitory effect on all three cell lines. However, the most potent response was observed in the HeLa cells, with the IC50 value approximately 200μM less than the other two cell lines. Analysis of the HeLa cells demonstrated that this activity occurred predominantly through induction of apoptosis but additionally by cell cycle arrest. We confirmed post-transcriptional degradation of the HPV18 viral oncogene E7. This decrease was dose dependent and appeared to correlate with an observed G1 arrest. In addition, it was demonstrated that a decrease in COX activity may be partially responsible for the anti-proliferative activity of sulindac.
Conclusions: This data indicates that the antineoplastic activities of sulindac are multifaceted. Since most cancers progress through the action of multiple pathways, drugs that simultaneously block several pathways might be particularly effective as therapeutic agents. Therefore, these results suggest that NSAIDs may offer potential as novel therapeutics for cervical cancer.
Category: Gynecologic & Obstetrics
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 220, Tuesday Morning