Selective toxicity of rose bengal to ovarian cancer cells in vitro

Paper here. Published June 30, 2012.

Author: Steven B. Koevary, Department of Biomedical Sciences and Disease, New England College of Optometry & Department of Cell Biology, University of Massachusetts Medical School

Abstract: Rose bengal (RB) has been utilized as a photodynamic agent for the targeted killing of cancer cells. Recent data suggest that intralesional RB alone may be effective in chemoablating locoregional and metastatic melanomas. The ability of RB to induce direct and bystander melanoma cell death led to the speculation that it may be similarly effective in the treatment of other neoplasms. The objective of this study was to determine whether RB can limit the growth, or kill, ovarian cancer cells in vitro. Ovarian carcinoma cells with or without a germline BRCA1 mutation were cultured with up to 800 µM RB for one hour or four days, after which their ability to proliferate was assessed using the MTT assay. Control cells included an embryonic kidney cell line transformed with adenovirus, and normal human fibroblasts. Ovarian cancer cells exhibited significant dose-dependent suppression of growth in response to RB; this suppression was similar to that seen with carboplatin. RB treated ovarian cancer cells appeared rounded, shrunken, and damaged. RB also inhibited the growth of kidney tumor cells but was much less effective in slowing the growth of normal human fibroblasts suggesting that RB-mediated growth suppression might be tumor cell specific. Ovarian cancer cells treated with RB displayed a significant increase in apoptosis that peaked at approximately four times the levels seen in untreated control cells. Furthermore, RB exposure resulted in the intracellular generation of reactive oxygen species (ROS) at levels that were significantly greater than in untreated cells and similar to levels seen in cells treated short term with H2O2. These data suggest that RB may not only suppress ovarian cancer cell growth but also induce their apoptotic cell death, justifying the further investigation of the effects of RB in an animal model of ovarian cancer.  

"Thus, even when optimally debulked, many patients still exhibit tumor nodules too small to have been resected by even the most skilled surgeon that likely seed future growths. In light of the above data, it is theorized that injection of these nodules with RB at the time of surgery may prove to be an effective strategy for not only their elimination, but for vaccinating patients against the future regrowth of gross tumors. This notion is supported by data that showed that PV-10 treatment increased the levels of tumor infiltrating lymphocytes and that the overall survival of ovarian cancer patients was greater in patients whose tumors contained T cells."