Growth inhibition of rat liver epithelial tumor cells by monoterpenes does not involve Ras plasma membrane association

Abstract

The role of altered ras oncoprotein (Ras) farnesylation and membrane association in the growth inhibitory effects of several monoterpenes (limonene, perillic acid, perillyl alcohol, menthol, pinene and cineole) was investigated in rat liver epithelial cells. All of the above compounds except cineole inhibited the growth of viral Ha-ras-transformed rat liver epithelial cells (WB-ras cells) at concentrations of 0.25-2.5 mM. These cells, however, were not necessarily more sensitive to these compounds compared to non-transformed and viral raf-transformed rat liver epithelial cells. Growth inhibition by limonene, perillic acid and pinene was only partially restored (20-50%) by supplementing the culture medium with 2 mM mevalonic acid. Western blot analyses of cytosolic and membranous fractions of WB-ras cells treated with monoterpenes indicated no change in Ras distribution. In contrast, lovastatin, a potent inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase and Ras farnesylation, specifically reduced WB-ras cell growth and increased cytosolic levels of Ras. Thus, monoterpene-induced growth inhibition of rat liver epithelial cells was dissimilar to lovastatin and did not appear to involve altered Ras plasma membrane association.

Gum mastic inhibits the expression and function of the androgen receptor in prostate cancer cells

“…Many monoterpenes, including ␣-pinene, may exhibit anticancer activities. 46,48 Based on the current results, we speculate that the major component of gum mastic, ␣-pinene, may be the active compound for repressing AR expression in LNCaP cells, although we cannot rule out the possible involvement of other components in gum. Because other gum resins can be administered systemically for disease treatments in animal models, 46,47 we expect that gum mastic or its active components may be useful in vivo for prostate cancer prevention and treatment.…”

Anthelmintic activity in vitro of Citrus sinensis and Melaleuca quinquenervia essential oil from Cuba on Haemonchus contortus

“…Limonene studies have also shown antitumor effect against some cancers. The growth of viral Ha-ras-transformed rat liver epithelial cells was inhibited by limonene (Ruch and Sigler, 1994). Limonene also inhibits the development of gastric cancers through increased apoptosis and decreased DNA synthesis (Uedo et al, 1999).…”

A Novel Temozolomide–Perillyl Alcohol Conjugate Exhibits Superior Activity against Breast Cancer Cells In Vitro and Intracranial Triple-Negative Tumor Growth In Vivo

“…46 and 47). As well, it has been described as a farnesyl-transferase inhibitor that results in the blockage of ras oncoprotein activity (48,49), although this has been challenged (50,51). Importantly, in all these cases relatively high concentrations of POH (well above 100 mmol/L) are required to achieve 50% inhibition of target activity (see also Fig.…”