Differential cytoprotective effect of squalene in a neuroblastoma vs. bone marrow model of cisplatin induced toxicity Bikul Das, Herman Yeger, Melvin Freedman, Gideon Koren, Sylvain Baruchel New Agent and Innovative Therapy Program, Hospital for Sick Children and Institute of Medical Science, University of Toronto, Toronto, ON, Canada; New Agent and Innovative Therapy Program, Hospital for Sick Children, Toronto, ON, Canada; New Agent and Innovative Therapy Program,Hospital for Sick Children, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada. Background: The development and potential application of cytoprotective agents that preferentially protect normal cells but not malignant cells from cytotoxic agents constitute a major therapeutic challenge. We investigated the cytoprotective ability of squalene, an isoprenoid antioxidant against cisplatin induced bone marrow (BM) toxicity. Methods: The growth inhibitory effect of squalene (squalene iP6, Isshogenki Corporation) against neuroblastoma cell line, SKNSH was tested in monolayer culture and colony formation in agarose. Flow cytometry and TUNNEL assay were done to characterize the growth inhibitory property of squalene. Selective cytoprotection of squalene against cisplatin induced BM toxicity was tested using a human BM progenitor colony assay grown in a methylcellulose media (MethocultTM,GFH4434, Stem Cell Inc., BC, Canada). Data analysis was done by One Way ANOVA. Results: Long term treatment of squalene (25-50 uM for 8 days) inhibited the growth of SKNSH cells by 20-35 % (P < 0.01). Exposure to squalene (12.5-50uM) for 10 days induced morphological changes in SKNSH cell line; large S type cells were seen to predominate the culture. Cell cycle analysis showed G0/G1 arrest in 25-50 uM dose range and TUNNEL assay showed 32% apoptosis in 50 uM treated group in SKNSH cell line. Squalene (50uM) also enhanced the residual cell killing ability of cisplatin in SKNSH cell line (p = 0.06443). On the other hand squalene demonstrated BM protective effect against cisplatin-induced cytotoxicity. Squalene (25uM) protected 4 weeks old human bone marrow CFU-GM and CFU-BEMM colonies from cisplatin induced toxicity (see table). Morphologically, squalene treated group revealed healthy and relatively bigger sized CFU-GEMM colonies compared to cisplatin treated group. In addition, squalene stimulated the total BM colony growth; 12.5 uM squalene increased the total BM colonies by 41.8 % (p= 0.001). The above findings demonstrate that squalene has selective action in normal versus cancer cell that make it a potential candidate for cytoprotective therapy. Squalene may also be used to stimulate the bone marrow in a situation of marrow failure. Ann's NOTE: This is excellent news. What this study demonstrates is that the action of cisplatin was enhanced in the cancer cells with the use of squalene, yet normal cells were protected from some of the adverse effects of chemotherapy. More evidence that natural products may enhance conventional therapy (complementary medicine) without limiting its effects against cancer AND still protect the normal cells. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.