The Durk Pearson & Sandy Shaw^®
Life Extension News^TM
Volume 6 No. 1 • February 2003

Lycopene Interferes with Cell Progression and IGF-1 Signaling in Mammary Cancer Cells

There is evidence that IGF-1 (insulinlike growth factor 1) signaling may play a role in certain cancers (such as prostate, breast, lung, and colorectal in women) by acting as a mitogen (a substance that increases cell proliferation) and inhibiting apoptosis (programmed cell death). In observational studies, higher levels of IGF-1 are associated with higher risks of these and possibly other cancers.¹ Hence, interfering with IGF-1 signaling, especially if such interference can be localized to high-risk tissues sensitive to its mitogenic effects,² would be very desirable in terms of reducing cancer risk.

A recent paper⁸ reports that, in mammary cancer cells, growth stimulation by IGF-1 was markedly reduced by lycopene treatment. The researchers note that these effects were not associated with changes in the number or affinity of IGF-1 receptors, but were a result of an increase in membrane-associated IGF-binding proteins, which were shown previously to negatively regulate IGF-1 receptor activation in different cancer cells. Moreover, they report that lycopene inhibited basal and IGF-induced thymidine incorporation into DNA (as a measure of growth) and slowed cell cycle progression, while not causing cell death. These same authors had previously reported that lycopene inhibited mammary, endometrial, and lung cancer cell growth in a dose-dependent manner; the concentration causing 50% inhibition was approximately 2 microM. The latter inhibition was detected after 24 hours of incubation and was maintained for at least three days.

References

1. See, e.g., a review by Yu and Rohan, Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 92(18):1472-89 (2000).
2. On the other hand, IGF-1 has shown protective effects in the pathogenesis of diabetic angiopathy,³ in accelerating muscle and motor neuron regeneration,⁴ in enhancing DNA accretion and growth in skeletal muscle,⁵ and possibly in enhancing the removal of amyloid-beta from the brain.⁶ Recently, transgenic mice (which had one gene for the IGF-1 receptor knocked out, while the other gene was normal) had greater resistance to oxidative stress and lived an average of 26% longer than their wild-type littermates (the 16% increase in lifespan for the male mice was not statistically significant, however; the male mice, but not females, also had abnormal blood glucose regulation).⁷ Hence, the overall picture for the risk/benefit of IGF-1 is decidedly complex.
3. Janssen and Lamberts. Circulating IGF-1 and its protective role in the pathogenesis of diabetic angiopathy. Clin Endocrinol 52:1-9 (2000).
4. Rabinovsky et al. Targeted expression of IGF-1 transgene to skeletal muscle accelerates muscle and motor neuron regeneration. FASEB J (Nov. 1, 2002).
5. Fiorotto et al. Persistent IGF-1 overexpression in skeletal muscle transiently enhances DNA accretion and growth. FASEB J (Nov. 15, 2002).
6. Carro et al. Serum insulin-like growth factor 1 regulates brain amyloid-beta levels. Nature Med 8(12):1390-7 (2002). See last issue of this newsletter for discussion.
7. Holzenberger et al. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421:182-7 (2003).
8. Karas et al. Lycopene interferes with cell cycle progression and insulin-like growth factor 1 signaling in mammary cancer cells. Nutr Cancer 36(1):101-111 (2000).