Monoterpenes such as limonene and perillyl alcohol (PA) are currently under investigation for their chemotherapeutic properties which have been tied to their ability to
Bb has a PKC INHIBITOR...which MIGHT BE (looks to be) a PKC DELTA INHIBITOR:
At the same time, PKC (delta symbol) is inactivated by tyrosine phosphorylation, resulting in defective apoptosis.
Stuart Yuspa described the use of a PKC -expressing adenovirus to show that the active kinase migrates to the mitochondria and induces cell death (28) .
***If tyrosine phosphorylation of PKC is blocked, cell differentiation takes place instead.***
Both events are potential targets for prevention. One can envision combinations of targets, one to restore the differentiation program, and another to cause cell death later in the process.
Class IV Targets: Known and Unknown Molecular Targets of Preventive Dietary Modifications Target(s) of Monoterpenes.
Monoterpenes (e.g., limonene, POH) are common compounds derived from the essential oils found in fruits and vegetables. They selectively inhibit cell proliferation via a G1 block, inducing apoptosis (44) . Limonene reduces N-nitrosomethylurea-induced mammary carcinogenesis from two tumors to less than one-half tumor/animal
but is toxic in preventive doses.
POH, commonly found in the sushi leaf, has a low-grade GI toxicity even at high dosages. Initial results with POH give encouraging hints of prolonged stable disease in prostate cancer, breast cancer, chronic myelogenous leukemia, and ovarian and rectal cancer.
Talin is a cytoplasmic protein that is concentrated at points of *cell adhesion*, membrane ruffles, the leading lamellae of the cell periphery and aligned with microfilament bundles, which acts to link cytoskeletal proteins to the integrins, thereby linking the extracellular matrix to other cells.
Talin is a large dimeric protein and is post-translationally modified through phosphorylation by protein kinase C-delta
(Litchfield and Ball, Biochem. Biophys. Res. Commun ., 1986, 134, 1276-1283; Watters et al., Exp. Cell. Res ., 1996, 229, 327-335) as well as by proteolytic cleavage events making it a central component of many signaling cascades.
Limonene inhibited isoprenylation of a class of cellular proteins of 21- *26 kDa*, including p21ras and possibly other small GTP-binding proteins, in a dose-dependent manner in both cell lines.
In contrast, limonene did not affect the isoprenylation of several other proteins, including nuclear lamins. Limonene is metabolized extensively in vivo but not in cultured cells.
The two major rat serum metabolites of limonene, perillic acid and dihydroperillic acid, were more potent than limonene in the inhibition of isoprenylation.
***These results demonstrate that limonene selectively inhibits isoprenylation of 21-26-kDa proteins*** at a point in the mevalonic acid pathway
distal to 3-hydroxy-3- methylglutaryl coenzyme A reductase,
and they provide a plausible explanation for its chemotherapeutic activity. Inhibition of isoprenylation of proteins such as p21ras and other small GTP-binding proteins would alter their intracellular localization and, hence, disrupt their biological activity.
B. burgdorferi Sh-2-82 produced an outer membrane protein different in size, i.e.,
26 kDa,
but with properties similar to those of to the protein from strain B31, suggesting variation in B. burgdorferi Tbps. (transferrin binding protein - iron implications)
Borrelia burgdorferi Proteomic liquid chromatography-tandem mass spectrometry analysis of tryptic fragments derived from strain B31 culture supernatants confirmed the identity of the 28-kDa species as Oms28 and
revealed a 26-kDa protein as 5′-methylthioadenosine/S-adenosylhomocysteine nucleosidase (Pfs-2),
Outer surface protein C (OspC) is a differentially expressed major surface lipoprotein of Borrelia burgdorferi. ospC is swiftly upregulated when spirochetes leave the Ixodes scapularis tick gut, migrate to the salivary gland, and exit the arthropod vector.
Here we show that OspC strongly binds to the tick salivary gland, suggesting a role for OspC in spirochete adherence to this tissue.
OspC is a major 23-kDa protein expressed by B. burgdorferi during transmission of spirochetes from ticks to mammals as well as in the vertebrate host (13, 14).
(Note: RECENT research suggests ``they'' are trying to make a vaccine to OspC.)
The chemoprevention of cancer by mevalonate-derived constituents of fruits and vegetables. Elson CE, Yu SG. Department of Nutritional Sciences, University of Wisconsin, Madison 53706-1571. J Nutr 1994 May;124(5):607-14 A nutritive isoprenoid constituents of fruits, vegetables, cereal grains and essential oils exhibit a spectrum of anticarcinogenic activities. The induction of hepatic Phase II detoxifying activities by dietary isoprenoids appears to underlie their blocking action. The second anticarcinogenic action of the dietary isoprenoids, suppression of the growth of chemically initiated andtransplanted tumors is, we suggest, secondary to the inhibition of mevalonate pathway activities.
Mevinolin, a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase activity, depletes cells of the intermediate products of the pathway that are required for the posttranslational modification of proteins, a process giving the proteins lipophilic anchors that bind to membranes.
As a consequence, nuclear lamins and ras oncoproteins remain in nascent states, and cells do not proliferate. gamma-Tocotrienol, perillyl alcohol, geraniol and
***d-limonene suppress hepatic HMG-CoA reductase activity, a rate-limiting step in cholesterol synthesis, and modestly lower serum-cholesterol levels of animals.***
These isoprenoids also suppress tumor growth. The HMG-CoA reductase of neoplastic tissues differs from that of sterologenic tissues in being markedly resistant to sterol feedback inhibition. Our review suggests that the mevalonate pathway of tumor tissues is uniquely sensitive to the inhibitory actions of the dietary isoprenoids.
Salonen T, Sareila O, Jalonen Y, Kankaanranta H, Tuominen R and Moilanen E (2006) Inhibition of classical PKC isoenzymes downregulates STAT1 activation and iNOS expression in LPS-treated murine J774 macrophages. British Journal of Pharmacology 147 790-799
Merry Christmas from Florida! Have some nice fresh squeezed juice!
Posts: 9424 | From Sunshine State | Registered: Mar 2001
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TerryK
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Marnie - so glad to see you back! I've missed you!!
It will take awhile to digest this new info. Thanks for posting it.
Merry Christmas to you too.
Terry
Posts: 6286 | From Oregon | Registered: Jan 2006
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This d'limonene is in TKO Orange, which kills ticks and bugs on impact, and keeps them away from any sprayed area. It's what I've been using as my nontoxic bug repellant.
It's also a fantastic cleaner. It cleaned my walls successfully after the fire exposure, and that's saying alot, as I had two fire restoration companies come over and I got sick from exposure to their cleaning products.
Posts: 13116 | From San Francisco | Registered: May 2006
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treepatrol
Honored Contributor (10K+ posts)
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