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Life Extension Magazine

LE Magazine November 2000

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References on Page 5

imageBroccoli: a wealth of phytochemicals

Broccoli may contain more cancer-preventing nutrients than any other plant. In 1992, scientists identified a broccoli compound called sulforaphane that helps mobilize the body’s natural cancer-fighting resources and reduces the risk of developing cancer.(54-60)

Sulforaphane has been shown to block the formation of tumors initiated by chemical carcinogens. Moreover, sulforaphane has been demonstrated to induce cancer cell death via the apoptosis (natural cell death) process.(61,62) A large amount of data shows that sulforaphane and other broccoli compounds act as cancer chemopreventive agents by favorably modifying carcinogen metabolism via modulation of both Phase 1 and Phase 2 detoxification enzyme systems.(62-66) These results suggest that broccoli compounds prevent cancer by activating detoxifying enzyme systems and inducing cancer cell apoptosis.

Phase II detoxifying enzymes, such as glutathione S-transferase, play an important role in the detoxification of chemical carcinogens. Recent studies have demonstrated that sulforaphane not only induces beneficial glutathione S-transferases but also inhibits of some major P450 enzymes that block the detoxification of organic poisons.(64,67,68)

Studies show that high human gastrointestinal tissue levels of glutathione S-transferase protect against a wide range of cancers. One study showed that a sulforaphane analog increased glutathione-S-transferase activity in all organs studied including the small intestine, liver and stomach. This study showed sulforaphane to be more potent than indole-3-carbinol in boosting beneficial glutathione S-transferase.(68)

Inhibiting DNA-adduct formation is known to reduce incidence of mammary tumor incidence. Sulforaphane was shown in one study to inhibit chemical-induced DNA adduct formation by 68% to 80%, suggesting that this extract from broccoli may function as a breast cancer preventive.(64) On the basis of mechanisms of carcinogenic effects cigarette smoke, sulforaphane appears to be a component in the prevention of lung cancer.

imageBroccoli contains a high percentage of D-glucarate compared to most plants studied. As mentioned earlier in this article, D-glucarate is critical in maintaining the important glucuronidation detoxification process.

Broccoli provides a cornucopia of carotenoids and other nutrients that provide a wide range of health benefits. The new Life Extension Mix contains a super-concentrated broccoli extract that is standardized to deliver precise amounts of sulforaphane and D-glucarate in each dose.

A potent flavonoid


Apigenin is a flavonoid found in parsley, artichoke, basil, celery and other plants. Over the last three years, a large number of published studies have demonstrated the anti-cancer properties of apigenin.

To study the effects of various plant constituents, an examination was made of 21 different flavonoids on the growth of human breast cancer cells. Apigenin was shown to the most effective anti-proliferative flavonoid tested.(69) A related study showed that flavonoids such as apigenin bind to estrogen receptor sites on cell membranes in order to prevent over-proliferation of these cells in response to estrogen.(70)

A study assessed the antioxidant potencies of several dietary flavonoids compared with vitamin C. Pretreatment with all flavonoids and vitamin C produced dose-dependent reductions in oxidative DNA damage. When ranked in order of potency, only apigenin, rutin and quercetin were more effective than vitamin C in reducing DNA oxidative damage.(71)

Apigenin was tested to ascertain its effect on human leukemia cells. Apigenin was shown to induce apoptosis more effectively than quercetin and other flavonoids tested. The researchers attributed a unique mechanism of inducing apoptosis to the cancer preventive activity of apigenin.(72) Another study showed that apigenin and another flavonoid called luteolin strongly inhibited the growth of human leukemia cells and induced these cells to differentiate.(73) Topoisomerases are involved in many aspects of leukemic cell DNA metabolism such as replication and transcription reactions. In one study, quercetin or apigenin were shown to inhibit topoisomerase-catalyzed DNA irregularities.(74) In a study of various agents used to induce differentiation of human promyelocytic leukemia cells, apigenin and luteolin were among the flavonoids shown to cause these leukemia cells to mature into healthy moncytes and macrophages.(75)

In studies against thyroid cancer cell lines, apigenin and luteolin were the most effective inhibitors found. Apigenin was shown to inhibit cancer cell signal transduction and induce apoptosis. The scientists concluded that apigenin may provide a new approach for the treatment of human anaplastic thyroid carcinoma for which no effective therapy is presently available.(76) Another study compared the effects genistein, apigenin, luteolin, chrysin and other flavonoids on human thyroid carcinoma cell lines. Among the flavonoids tested, apigenin and luteolin were shown to be the most potent inhibitors of these cancer cell lines. The scientists noted that because these thyroid cancer cells lacked an anti-estrogen receptor binding site and an estrogen receptor, that apigenin and luteolin are inhibiting these cancer cells via previously unknown mechanisms. The scientists concluded that apigenin and luteolin may represent a new class of therapeutic agents in the management of thyroid cancer.(77)

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In a study on colorectal cancer cell lines, apigenin or quercitin were shown to interfere with epidermal growth factor cell stimulation. The researchers speculated that these flavonoids could be primary components in fruits and vegetables that reduce the risk colorectal cancer by inferring with the cancer cell growth signaling pathway.(78)

The epidermal growth factor signal transduction pathway is an essential component of both cancer cell growth and differentiation. Certain gelatinases are expressed in human cancers and are thought to play a critical role in tumor cell invasion and metastasis. Apigenin was shown to inhibit these gelatinases and interfere with the growth factor signaling pathways. The scientists concluded that compounds like apigenin may provide a novel means of controlling growth and invasive potential of certain tumors via these dual mechanisms.(79) In a related study, apigenin was shown to prevent the degradation of tissue components by cultured human carcinoma cells, a mechanism by which cancer spreads to other parts of the body.(80)

The soy isoflavone genistein has been shown to be a potent inhibitor of cancer cell proliferation and in vitro angiogenesis. Moreover, the concentration of genistein in the urine of subjects consuming a plant-based diet is 30-fold higher than that in subjects consuming a traditional Western diet. Scientists have found in one study that apigenin and luteolin are more potent cancer inhibitors than genistein, and suggest that these plant components may contribute to the preventive effect of a plant-based diet on chronic diseases, including certain cancers. The scientists noted that the consumption of a plant-based diet can prevent the development and progression and growth of solid malignant tumors.(81)

Protein kinase C is over-expressed in many human tumors. One group of scientists has shown that apigenin blocks several points in the process of tumor promotion, including inhibiting kinases, reducing transcription factors and regulating cell cycle.(82) Another group of scientists showed that apigenin and other flavonoids inhibit prostate cancer cell growth by blocking tyrosine kinase activity.(83) Moreover, another study demonstrated that apigenin blocks mammary cell proliferation induced by several kinase-related pathways.(84)

The mutation and oxidation of estrogens is related to the development of certain cancers. The favorable influence of apigenin, genistein and other flavonoids on estrogen metabolism led researchers in one study to speculate that these plant extracts could be used in the prevention or treatment of estrogen-related diseases.(85)

Another mechanism by which cells mutate into malignancies involves a process known as sulfation. One study showed that apigenin and ellagic acid were potent inhibitors of sulfation compared to quercetin.(86)

In a study on human promyelocytic leukemia cells, genistein, followed by apigenin and daidzein, were the most potent inhibitors of toxic free radical byproducts generated by these leukemia cells. Other flavonoids showed no effect. The scientists stated that the antioxidant effects of these flavonoids may contribute to their chemopreventive potentials against human cancers.(87)

Seven men and seven women participated in a randomized crossover trial to study the effect of intake of parsley, containing high levels of apigenin, on biomarkers for oxidative stress. This basic diet was supplemented with parsley providing 3.73-4.49 mg apigenin in one of the intervention weeks. The scientists observed increased activity of the natural antioxidants glutathione reductase and superoxide dismutase in red blood cells during intervention with parsley as compared to people taking the basic diet without added parsley.(88)

A group of scientists studied the potential preventive effects of skin tumor promotion by apigenin. When topically applied, apigenin was shown to inhibit UV-induced skin tumorigenesis in mice. The scientists observed that apigenin facilitated several tumor suppressor factors including the important p53 binding activity.(89)

Grape skin and red wine contain resveratrol, which has been shown to inhibit platelet aggregation both in vivo and in vitro. One study showed that genistein, daidzein or apigenin produced inhibitory effects against an underlying cause of abnormal platelet aggregation similar to those seen with resveratrol.(90)

imageIn order to better understand the mechanisms by which apigenin may prevent cancer, scientists looked at the effects this flavonoid would have on new blood vessel growth. Apigenin was shown to inhibit some factors involved in the process of tumor angiogenesis (new blood vessel growth that feeds rapidly dividing cells).(91)

Many types of cancer cells use cyclooxygenase-2 (COX-2) to propagate. COX-2 inhibiting drugs are being prescribed to cancer patients to slow the growth of existing tumors. One study showed that apigenin or genistein also suppresses formation of COX-2. The scientists conducting this study suggest that apigenin and related flavonoids may be important in the prevention of cancer and inflammation, partly via their COX-2 inhibiting properties.(92)

These studies as a whole provide a basis for cancer patients to consume a diet rich in certain fruits and vegetables as an adjunctive treatment for their disease. Apigenin is an antioxidant flavonoid with chemopreventive properties. It has been shown to arrest the growth of cancer cells, with concomitant inhibition of intracellular signaling cascades and decreased oncogene expression.

The Life Extension Foundation first introduced apigenin in 1985, but was unable to find a standardized plant extract that could consistently provide a specific number of milligrams per dose. The new Life Extension Mix contains a plant concentrate that provides 10 to 18 mg of apigenin and apigenin 7-glucoside per daily dose. Apigenin 7-glucoside is broken down into apigenin in the small intestine where it is absorbed.

Continued on Page 3
References on Page 5

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