Post on 10-Apr-2018
transcript
8/8/2019 Tocotrienols From Palm Oil as Anticancer Drugs
1/13
Tocotrienols from Palm Oil as
anticancer drugs
8/8/2019 Tocotrienols From Palm Oil as Anticancer Drugs
2/13
Tocotrienols
Natural vitamin E four saturated analogues (, , , and ) tocopherols
four unsaturated analogues (, , , and ) tocotrienols
In many cereal grains (ie. oat, barley, and rye, rice bran) and
in palm oil, there are more tocotrienols than tocopherols Crude palm oil extracted from the fruits ofElaeis guineensis
particularly contains a high amount of tocotrienols ,particularly rich source of (, , and ) tocotrienol
8/8/2019 Tocotrienols From Palm Oil as Anticancer Drugs
3/13
Natural sources of tocotrienols
8/8/2019 Tocotrienols From Palm Oil as Anticancer Drugs
4/13
Content of tocotrienol and tocopherol isomers
from various sources.
8/8/2019 Tocotrienols From Palm Oil as Anticancer Drugs
5/13
8/8/2019 Tocotrienols From Palm Oil as Anticancer Drugs
6/13
8/8/2019 Tocotrienols From Palm Oil as Anticancer Drugs
7/13
8/8/2019 Tocotrienols From Palm Oil as Anticancer Drugs
8/13
8/8/2019 Tocotrienols From Palm Oil as Anticancer Drugs
9/13
Possible Mechanisms of Cancer Inhibition
by Tocotrienol
T3> T3> -T3> -T> -T> -T
Antioxidant Potency: Reduction of lipid peroxidationand formation of reactive products prevent DNA
mutations that increase the risk of cancer. Tocotrienol may inhibit cancer by the quenching of free
radicals, or increase the efficacy of anti-tumor actionsby strengthening the immune system.
Double bonds in the isoprenoid side chain -tocotrienolsmove freely and more efficiently within cellmembranes than tocopherols, giving tocotrienolsgreater ability to catch and fight free radicals.
8/8/2019 Tocotrienols From Palm Oil as Anticancer Drugs
10/13
Apoptosis Activation: Basically, apoptosis is an encoded suicide program
designed to protect cells from becoming cancerous.When this process does not work cancer develops.
Tocotrienols are effective promoters of apoptosis. Tocotrienol may stimulate death receptors such as
tumor necrosis factor (TNF) and Fas, which leads toactivation of caspases, including caspase-8, -9, and 3. Activation of these caspases mediates the various
cytoplasmic and nuclear events associated withapoptosis. A recent study showed that gamma-tocotrienol stimulates a rise in caspase-8, -9, and -3,thereby inducing apoptosis.
8/8/2019 Tocotrienols From Palm Oil as Anticancer Drugs
11/13
Anti-proliferation Further studies on tocotrienol and breast cancer indicated that
gamma-tocotrienol targets cancer cells by inhibiting Id1, a keycancer-promoting protein. Gamma-tocotrienol was shown totrigger cell apoptosis and well as anti-proliferation of cancercells.
The antiproliferative effect of isoprenoids is thought to be dueto suppression of the mevalonate pathway, through whichmutated ras proteins transform healthy cells into cancer cells.Mutated ras is the most common cellular defect found in humancancers. The mevalonate pathway escapes regulatory control intumor tissue but remains highly sensitive to regulation by toco-trienols. Tocotrienols are at least five times more powerful thanfarnesol, the body's regulator of the mevalonate pathway
8/8/2019 Tocotrienols From Palm Oil as Anticancer Drugs
12/13
Angiogenesis Inhibition: Recent studies showed thattocotrienols but not tocopherols inhibit angiogenesis,an indispensable step in tumor growth. Vascularendothelial growth factor (VEGF) regulates
angiogenesis by binding to VEGF receptor (VEGFR
) inendothelial cells. Tocotrienol may downregulateVEGFR, therefore blocking intracellular signaling ofVEGF and inhibiting angiogenesis. Since angiogenesis isessential to tumor growth, its inhibition may likely
prevent cancer metastasis.
8/8/2019 Tocotrienols From Palm Oil as Anticancer Drugs
13/13
Gamma-tocotrienols was shown to be three times
more potent in inhibiting growth of human breastcancer cultured cells than chemotherapy drugtamoxifen (standard treatment of breast cancer).
Tocotrienols in combination with tamoxifen were more
inhibitory than either compound alone in bothestrogen-responsive and nonresponsive breast cancercells. The synergism between tamoxifen andtocotrienols may allow for the use of lower doses oftamoxifen and reduce its risk of adverse side effects.
Tocotrienols could be a good means as complement tothe chemotherapy of breast cancer.