Carotenoids, as Promising Factor for Functional Foods - ACS

Sep 24, 1998 - Chapter 6, pp 59–70. DOI: 10.1021/bk-1998-0701.ch006. ACS Symposium Series , Vol. 701. ISBN13: 9780841235724eISBN: 9780841216747...
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Chapter 6

Carotenoids, as Promising Factor for Functional Foods

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H. Nishino Department of Biochemistry, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyoku, Kyoto 602, Japan

Various natural carotenoids, besides β-carotene, were proven to have anticarcinogenic activity, and some of them, such as α-carotene, showed higher potency than β-carotene. Furthermore, some of these natural carotenoids show more potent antioxidative activity than βcarotene. Thus, these carotenoids (α-carotene, lutein, zeaxanthin, lycopene, β-cryptoxanthin and phytoene), as well as β-carotene, may be applicable as active components in functional foods for the purpose of preventing oxidative damage-related diseases, including cancer. In the case of phytoene, one of the anticarcinogenic carotenoids, the concept of "bio-chemoprevention", which means biotechnology-assisted method for chemoprevention, will be fitted. In Fact, the establishment of mammalian cells producing phytoene was accomplished by introducing the crt Β gene, which encodes phytoene synthase. These cells were proven to acquire the resistance against the oxidative stress. Phytoene-containing animal foods may be classified as a novel type of functional food, which has the preventive activity against diseases. It may also have the ability to reduce the accumulation of oxidized substances, which are hazardous for human health.

Information has been accumulated indicating that diets rich in vegetables and fruits can reduce the risk of a number of chronic diseases, including cancer, cardiovascular disease, diabetes and age-related macular degeneration. Various factors in plant foods, such as carotenoids, antioxidative vitamins, phenolic compounds, terpenoids, steroids, indoles and fibers, have been considered responsible for this reduction in risk. Among them, carotenoids have been widely studied and proven to show diverse beneficial effects on human health. Initially, carotenoids in vegetables and fruits were suggested to serve as precursors of vitamin A ; Vitamin A being the active

©1998 American Chemical Society

Shibamoto et al.; Functional Foods for Disease Prevention I ACS Symposium Series; American Chemical Society: Washington, DC, 1998.

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60 compound. In this context, β-Carotene has been studied most extensively, since βCarotene has the highest pro-vitamin A activity among carotenoids. However, Peto et al.(l) suggested that β-Carotene could have a protective effect against cancer without converting to vitamin A . Logically, then, carotenoids other than β-Carotene may also contribute to protection of cancer and various diseases. Of more than 600 carotenoids identified up to date, about 40 carotenoids are found in our daily foods. However, as a result of selective uptake in the digestive tract, only 14 carotenoids with some of their metabolites have been identified in human plasma and tissues. Thus, it was decided to evaluate the biological activities of only the carotenoids that are detectable in the human body. It was found that some of the carotenoids that were tested showed more potent activity than β-Carotene to suppress the process of carcinogenesis. In addition, antioxidative activity of α-carotene and lycopene was also proven to be higher than that of β-Carotene. Therefore, various natural carotenoids, besides β-Carotene, seem to be possible candidates as factors for functional foods. Initially, recent results of the evaluation for anticarcinogenic activity of the various natural carotenoids will be summarized, as the part of the basic data for the development of functional foods. Some of the natural carotenoids, such as phytoene, are unstable when purified, and thus, very difficult to examine the biological activities of them. In this context, we attempted to develop a new method for the synthesis of phytoene in animal cells. Discovery of mammalian cells producing phytoene was succeeded by the introduction of crt Β gene, which encodes phytoene synthase. These cells were proven to acquire the resistance against oxidative stress. Thus, the antioxidative activity of phytoene was proven. Anti-Carcinogenic Activity of Natural Carotenoids Among the carotenoids, α-carotene, lutein, zeaxanthin and lycopene are now being investigated, by international collaboration, as promising candidates for cancer prevention. This widespread investigation is, in part, due to the fact that these carotenoids are detectable in human plasma, and may have a more potent anticarcinogenic activity than β-carotene. α-Carotene. In recent studies, it was found that α-carotene induced the G1-arrest in the process of the cell cycle (2). Since various agents which induce G1-arrest have been proven to have cancer preventive activity, we evaluated anticarcinogenic activity of α-carotene. α-Carotene showed higher activity than β-carotene to suppress tumorigenesis in skin, lung, liver, and colon (3-4). In the skin tumorigenesis experiment, a two-stage mouse skin carcinogenesis modes were used. Seven-week-old ICR mice had their backs shaved with an electric clipper. Starting one week after initiation with 100μg of 7,12dimethylbenz[a]anthracene (DMBA), 1 ^ g of 12-O-tetradecanoylphorbol-13acetate (TPA) was applied twice a week for 30 weeks, a- or β-carotene (200 nmol) was applied with each TPA application. With this, greater potency of α-carotene

Shibamoto et al.; Functional Foods for Disease Prevention I ACS Symposium Series; American Chemical Society: Washington, DC, 1998.

Downloaded by NANYANG TECHNOLOGICAL UNIV on June 4, 2016 | http://pubs.acs.org Publication Date: September 24, 1998 | doi: 10.1021/bk-1998-0701.ch006

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over β-carotene was observed. The percentage of tumor-bearing mice in the control group was 68.8%, whereas the percentages of tumor-bearing mice in the groups treated with a- and β-carotene were 25.0% and 31.3% respectively. The average number of tumors per mouse in the control group was 3.73, whereas the a-carotenetreated group had 0.27 tumors per mouse (p