Preferential induction of apoptosis of leukaemic cells by farnesol

Rioja, Alphonso S.; Pizzey, Arnold; Marson, Charles M.; Thomas, N. Shaun B.

doi:10.1016/s0014-5793(00)01168-6

Cited by 57 publications

(43 citation statements)

References 23 publications

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“…One possibility is that g-T3H acts via inhibition of prenylation (Theriault et al, 2002). Indeed, other compounds, which block prenylation, have been shown to be strong apoptogens (Miquel et al, 1998;Rioja et al, 2000). It is tempting to hypothesise that compounds like g-T3H or g-T2H may prevent carcinogenesis by suppressing prenylation of crucial oncogenes, such as Ras (Adjei 2001), in which case these agents would have prophylactic effects.…”

Section: Resultsmentioning

confidence: 99%

Vitamin E analogues as inducers of apoptosis: structure–function relation

et al. 2003

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Recent results show that a-tocopheryl succinate (a-TOS) is a proapoptotic agent with antineoplastic activity. As modifications of the vitamin E (VE) molecule may affect its apoptogenic activity, we tested a number of newly synthesised VE analogues using malignant cell lines. Analogues of a-TOS with lower number of methyl substitutions on the aromatic ring were less active than a-TOS. Replacement of the succinyl group with a maleyl group greatly enhanced the activity, while it was lower for the glutaryl esters. Methylation of the free succinyl carboxyl group on a-TOS and d-TOS completely prevented the apoptogenic activity of the parent compounds. Both Trolox and its succinylated derivative were inactive. a-tocotrienol (a-T3 H) failed to induce apoptosis, while g-T3 H was apoptogenic, and more so when succinylated. Shortening the aliphatic side chain of g-T3 by one isoprenyl unit increased its activity. Neither phytyl nor oleyl succinate caused apoptosis. These findings show that modifications of different functional moieties of the VE molecule can enhance apoptogenic activity. It is hoped that these observations will lead to the synthesis of analogues with even higher apoptogenic and, consequently, antineoplastic efficacy.

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Section: Resultsmentioning

confidence: 99%

Vitamin E analogues as inducers of apoptosis: structure–function relation

et al. 2003

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“…A vouacapan diterpene, isolated from a Pterodon pubescens extract, was shown to reduce proliferation and induce apoptosis of melanoma cells (7). The compounds geranylgeraniol and farnesol were shown to induce tumor cell anti-proliferative effects (11) and apoptosis (12,13). Thus, different substances present in EEPp may be involved in its anti-leukemic effects.…”

Section: Discussionmentioning

confidence: 99%

Pterodon pubescens seed extract induces the cell cycle arrest of leukemic cells by deregulating cyclin D1 and E2 mRNA levels

Pereira

Simão²,

Dalmau³

et al. 2010

Oncology Letters

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Abstract. Plant-derived compounds are important sources of effective anti-cancer agents. Pterodon pubescens is a native Brazilian plant popularly known for its anti-inflammatory and anti-arthritic effects. The ethanolic extract of its seeds (EEPp) is a viscous, brown and fragrant oil containing geranylgeraniol, farnesol, naphthalene, dimethyldodecatrienol and vouacapan diterpene derivatives, in addition to other compounds. This study investigated the in vitro anti-leukemic properties of EEPp using the resistant human leukemia cell line K562. The EEPp anti-proliferative effect was demonstrated by the inhibition of DNA synthesis and cell growth, and the induction of cell cycle arrest in the G 1 phase. Furthermore, cyclin E2 mRNA levels were down-regulated, while those of cyclin D1 were up-regulated. An EEPp anti-leukemic effect may have also triggered apoptosis, as it increased the number of shrunken cells and phosphatidylserine cell membrane exposure. These observations suggest that EEPp deregulates cyclin D1 and E2 expression, inducing cell cycle arrest and apoptosis of leukemic cells.

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“…Farnesol is produced from FPP by farnesyl pyrophosphatase (21). It exhibits a wide variety of biological activities, including cell growth inhibition (22,23), induction of apoptosis (24,25), and vascular tone regulation (26)(27)(28). In the lipid metabolism, farnesol accelerates the degradation of HMG-CoA reductase (29)(30)(31)(32).…”

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confidence: 99%