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- Karlson, J., et al.
(författare)
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Inhibition of tumor cell growth by monoterpenes in vitro : Evidence of a Ras-independent mechanism of action
- 1996
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Ingår i: Anti-Cancer Drugs. - : Ovid Technologies (Wolters Kluwer Health). - 0959-4973 .- 1473-5741. ; 7:4, s. 422-429
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Tidskriftsartikel (refereegranskat)abstract
- (+)-Limonene (d-limonene) and related monoterpenes show chemopreventive activity against rodent mammary carcinoma and inhibit the growth of cancer cells in vitro, One suggested mechanism for the anti-tumorigenic effect of (+)-limonene is inhibition of the post-translational isoprenylation of growth controlling Pas oncoproteins. We have here examined the growth inhibitory effects of (+)-limonene and other related monoterpenes on PANC-1 pancreas carcinoma cells (carrying a K-ras mutation) and on 12V-H-ras-transformed rat fibroblasts, (+)- and (-)-perillyl alcohol, 7-methyl-perillyl alcohol, (+)-limonene oxide and (+)-perillic acid methyl ester were all found to efficiently inhibit cell growth at 1 mM, whereas (+)-limonene caused an approximately 50% growth reduction at 5 mM, Whereas BZA-BB, an inhibitor of Ras farnesyl transferase, was found to induce morphological reversion of 12v-H-ras-transformed cells, (+)-perillyl alcohol and (+)-limonene did not induce reversion. Furthermore, monoterpenes did not decrease MAP kinase enzyme activity or collagenase promoter activity in PANC-1 cells, two functions known to be down-stream from Pas, We conclude that although effective in inhibiting the growth of tumor cells harboring activated res oncogenes, limonene and (+)-perillyl alcohol are unlikely to act by inhibiting Ras function.
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