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These results not only provide a novel molecular mechanism for the anticancer effect of oridonin in colorectal cancer, but also suggest oridonin could be a novel FAS inhibitor in cancer treatment. These results strengthen the scientific basis for the therapeutic use of oridonin in colorectal cancer.

The tumor promoters 12-O-tetradecanoyl-phorbol-13-acetate and teleocidin markedly enhanced the transformation of C3H 10T1/2 mouse fibroblasts when these cells were transfected with the cloned human bladder cancer c-rasH oncogene. Transfection studies with the drug resistance marker gpt and time course studies indicate that this enhancement is not simply an effect on the process of DNA transfection. These findings, together with parallel studies with NIH 3T3 fibroblasts, also indicate that the competence of animal cells for DNA transfection is a function of the recipient cell line, the transfected marker, and the growth conditions. Our findings suggest that during multistage carcinogenesis tumor promoters may complement the function of activated cellular oncogenes.

Studies of a number of normal and carcinogen-transformed murine cell lines, and a variety of murine tissues, have indicated that, in contrast to several other cellular oncogenes, the oncogene c-mos gene is usually transcriptionally silent. The recent report by Rechavi et al. indicating that in the mouse myeloma XRPC24 originally induced by pristane (2,6,10-14-tetramethylpentadecane) the c-mos gene is rearranged and transcriptionally active, and that it can transform murine fibroblasts in a transfection assay, is therefore of considerable interest. Here we show that the c-mos locus has undergone a similar rearrangement, and is also transcriptionally active, in the cell line P3-X63-Ag8-653, a derivative of the mouse myeloma MOPC 21 which was induced by mineral oil. This line is widely used for making hybridomas that synthesize monoclonal antibodies. We also demonstrate that the rearranged c-mos sequence is maintained in three different hybridomas derived by fusion of this cell line with normal murine spleen lymphocytes, suggesting that it may play a role in the continuous growth and/or constitutive immunoglobulin production by these hybridomas.