Squalene, Olive Oil, and Cancer Risk: Review and Hypothesis

Abstract

Epidemiologic studies of breast and pancreatic cancer in several Mediterranean populations have demonstrated that increased dietary intake of olive oil is associated with a small decreased risk, or no increased risk, of cancer, despite a high overall lipid intake. Experimental animal models in high dietary fat and cancer also indicate that olive oil either has no effect, or a protective effect, on the prevention of a variety of chemically induced tumors. As a working hypothesis, it is proposed that the high squalene content of olive oil, as compared to other human foods, is a major factor in the cancer-risk reducing effect of olive oil. Experiments in animal models suggest a tumor-inhibiting role for squalene. A mechanism is proposed for the tumor-inhibitory activity of squalene based on its known strong inhibitory activity of HMG-COA reductase catalytic activity in vivo, thus reducing farnesyl pyrophosphate (FPP) availability for "prenylation" of ras oncogene, which relocates this oncogene to cell membranes and is required for the signal-transducing function of ras. Reduction of mutated ras oncogene activation may be useful in breast and colon cancer and may be particularly applicable to pancreatic cancers that are strongly associated with ras oncogenes.

Olive oil protects against chromosomal aberrations induced by doxorubicin in wistar rat bone marrow cells

“…Experimental animal model studies of high dietary fat and cancer have also indicated that olive oil can help prevent a number of chemically induced tumors (Weijl et al, 1997). It has been proposed that squalene, found in olive oil, has a protective effect (Newmark, 1997). A favorable effect of olive oil has also been proposed, on the basis of other animal experiments, to be due to the presence of oleic acid, a monounsaturated fatty acid, and specific micronutrients, such as vitamin E (Braga et al, 1998).…”

Gemcitabine versus Modified Gemcitabine: A Review of Several Promising Chemical Modifications

“…66 Recent in vitro and in vivo model experiments suggest a tumour-inhibiting role for squalene. 67 Pr. Couvreur's team developed the concept of squalenoylation involving the chemical linkage of squalene with various nucleoside analogues which allowed the formation of novel colloidal nano-assemblies of 100-300nm with a narrow size distribution, after dispersion in an aqueous environment.…”

Involvement of steroid hormone and growth factor cross-talk in endocrine response in breast cancer.

“…farnesyl protein transferase (Kohl et al 1995, Reuveni et al 1997) or which act to lower Ras mRNA levels through the use of anti-sense oligonucleotides and ribozymes (Monia et al 1992, Kawada et al 1997, Scherr et al 1997. Many naturally occurring compounds also inhibit Ras function, often by preventing association with the membrane, including a Vinca alkaloid (Umezawa et al 1994), squalene (found in olive oil (Newmark 1997)), diallyl disulfide (found in garlic (Singh et al 1996)) and damnacanthal (Hiramatsu et al 1993).…”