Abstract A46: Ablack raspberry extract inhibits the proliferation of cervical cancer cells partially through proapoptotic effects

Abstracts: Frontiers in Cancer Prevention Research 2008 A46 Cervical carcinoma, the second most common female cancer worldwide, is the seventh leading cause of cancer death in women. Although pap smears to screen abnormal cervical cytology have helped reduce mortality rates, it remains a challenge to manage preinvasive and invasive cervical lesions. The long latency of cervical cancer allows preventive and therapeutic interventions before progressing onto invasive disease. Thus, phytochemical-based cancer chemoprevention and the role of bioactive food components have attracted significant interest in current cancer-fighting interventions. We have previously shown that lyophilized black raspberries (LBR, Rubus occidentalis ) inhibit the cell proliferation of human oral squamous cell carcinoma cells in vitro as well as oral tumorigenesis in vivo . Given the similar epidemiologic basis of oral and cervical cancers, we evaluated whether an LBR extract had anti-proliferative effects in cervical cancer cells in vitro and began to elucidate the possible regulatory molecular mechanisms. We found that LBR inhibited the proliferation of three human cervical cancer cell lines, HeLa (HPV16−/HPV18+) SiHa (HPV16+/HPV18−) and C-33A (HPV18−/HPV16−), in a dose-dependent manner (at 25, 50, 100 or 200µg/ml for 1, 3 and 5 days, respectively) to a maximum of 44%, 53% and 45% respectively (P<0.005). While exogenous hydrogen peroxide (H2O2, 100µM), a common reactive oxygen species (ROS) intermediate and inhibitor of cell growth, inhibited C-33A proliferation, HeLa and SiHa cells were not significantly affected. The anti-proliferative effects of either LBR or LBR+catalase were similar in all cell lines as shown by WST1 (tetrazolium salt cleavage) and crystal violet assays, which supporting the hypothesis that decreased proliferation is specific to LBR bioactive components and independent in vitro peroxide generation. Flow cytometric analysis of propidium iodide and Annexin V staining showed that LBR induced apoptotic markers in all three cells lines, and did not change cell cycle progression. LBR treatment induced hypercondensation and volume contracted nuclei in Hela cells as demonstrated by fluorescence microscopy analysis of Hoechst 33342 staining. In conclusion, an extract of lyophilized black raspberries demonstrated significant anti-proliferative and pro-apoptotic activities in human cervical cancer cells in vitro . Therefore, black raspberries and their bioactive components may represent promising candidates for the phytochemical-based chemoprevention of cervical cancer and warrant further investigation. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A46.