D-limonene: Anti-Proliferative Effects-Human Prostate Ca Cells

Anti-proliferative effects of D-limonene on human prostate carcinoma cells

Shawn Trokhan, Sanjay Gupta.

Case Western Reserve University, Cleveland, OH.

Prostate cancer is clinically diagnosed in 1 of every 11 men in the United States and one-third of those diagnosed will eventually develop metastatic form of the disease.

Prostate cancer often progress from a hormone-sensitive, non-metastatic phenotype to a hormone-insensitive and chemotherapy-resistant phenotype with highly invasive and metastatic growth properties.

Most prostate cancers respond initially to androgen ablation however, the residual androgen-insensitive cells recolonize, expand and ultimately establish hormone-resistant state. Also, at the time of clinical diagnosis most prostate cancers represent a mixture of androgen-sensitive and androgen-insensitive cells.

Therefore, the key to the control of prostate cancer appears to lie in the elimination of both types of cells through mechanism-based preventive or therapeutic approaches. D-limonene, a plant-derived monocyclic monoterpene commonly present in orange and other citrus peel oil has shown promise in the prevention or therapy of some cancer types.

D-limonene is probably present in high levels in the Mediterranean diet and may be an important component in putative cancer-preventive effect of such diet.

Employing LNCaP as androgen-sensitive and DU145 as androgen-insensitive human prostate carcinoma cells, specifically we first established the anti-proliferative effects of D-limonene and then determined the mechanism of its action.

D-limonene (1-10 mM) treatment resulted in dose- and time- dependent (i) inhibition of cell growth, (ii) decrease in mitochondrial activity, (iii) induction of necrosis in both cell types. D-limonene treatment (1-10 mM) showed minimal signs of apoptosis in both cell types and did not significantly affect the distribution of cells among different phases of the cell cycle.

These effects were found to correlate with a shift in Bax/Bcl2 ratio towards cell death in both cell types irrespective of the androgen association.

Taken together, this is the first study suggesting that D-limonene could be developed as an anti-cancer agent against prostate cancer.

AACR Abstract Number: 4773 2003

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