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

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http://www.annieappleseedproject.org/dlimanefpros.html

 

 

 

 

 

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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