Apoptosis induction therapy for pancreatic cancer cells by isoprenoids

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Geranylgeraniol (GGO) and farnesol (FO), synthetic isoprenoids, which are the side chain of vitamine K2, have been noted for their growth inhibitory-effect on hematological cells. However, the precise mechanisms of their functions are still unclear.We investigated the effect of GGO and FO on the proliferation of sex pancreatic cancer cell lines (Panc-1, MIAPaCa-2, AsPC-I, BxPC-3, 1B2C6, KP4) and fresh cancer cells, which were isolated from ascitis of three pancreatic cancer patients. GGO inhibited the proliferation of all these cancer cells at 20-70μM of IC50 and FO did at 20-60μM of IC50. GGO and FO stimulated DNA fragmentation of treated cells. Therefore, we studied on the signal transudation of apoptosis induced by GGO and FO. P53 is not to be implicated to apoptosis by GGO and FO, because all cell lines have deletion or mutation on p53 gene. We studied whether caspse family (ICE and CPP32) was involved in the effect of GGO or FO by using ICE and CPP32 inhibitors. Effect of GGO and FO were not affected by both inhibitors. Pancreatic cancer cells were inoculated in nude mise to study the effect of GGO and FO diminished the cancer tumors without obvious side effects.