Re:Dietary derived compounds in cancer chemoprevention - 녹차 카테킨, 다불포화지방산, 카로티노이드, 이소티오시안염, 비타민 D, 엽산, 칼슘, 셀레늄

[문형철]

beyond reason

미랑원소 치유의학의 세계

Contemp Oncol (Pozn). 2012; 16(5): 394–400. 

Published online 2012 Nov 20. doi: 10.5114/wo.2012.31767

PMCID: PMC3687449

PMID: 23788916

Dietary derived compounds in cancer chemoprevention

Ewa Langner1 and  Wojciech Rzeski1,2

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Abstract

Cancer chemoprevention is defined as the application of natural or synthetic agents to suppress or reverse cancer development and progression. In this field especially diet derived compounds have recently attracted researchers’ attention as potential therapeutics generally exerting low toxicity compared with regular drugs. This review presents a survey of recent findings concerning the most promising dietary chemopreventive agents such as green tea polyphenols (i.e. catechins), long-chain polyunsaturated fatty acids, carotenoids, glucosinolates/isothiocyanates, vitamins (i.e. vitamin D and folate) and minerals (i.e. calcium and selenium). Molecular targets involved in intrinsic pathways affected by these natural compounds are also shortly discussed.

- 암화학물질(Cancer chemoprevention)은 암의 발생과 진행을 자연 또는 합성물을 적용하여 억제하는 물질임

- 항암약물보다 독성이 거의 없음. 

- 이 논문에서는 녹차 폴리페놀(카테킨),  긴사슬 다불포화지방산, 카로티노이드, 이소티오시안염, 비타민 D, 엽산, 미네랄(칼슘, 셀레늄)에 대해 설명함. 

Keywords: cancer chemoprevention, green tea polyphenols, polyunsaturated fatty acids, glucosinolates, carotenoids

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Introduction

As there is overall agreement that preventing disease is more desirable than curing, a multitude of potential chemopreventive compounds are under investigation. The term chemoprevention, first introduced by Sporn, means inhibiting, suppressing or reversing cancer development and progression with the use of natural or synthetic agents [12, 34, 5

Different dietary patterns in distinct countries are related to higher or lower incidences of cancer development in these ethnic groups, which confirm‎s an inverse association between food borne preventive compounds and carcinogenesis. Lower incidence of breast, prostate and gastrointestinal tract cancer were always observed for Asian populations [6–8

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Diet-derived chemopreventive agents

For many years it has been believed that diet can influence various diseases and the impact is often positive for the human organism. It was suggested already two and half thousand years ago by Hippocrates, who said “Let food be thy medicine and medicine be thy food”. Diet can deliver both pro-healthy and harmful substances. Some can act as carcinogens and initiate or stimulate tumor growth. However, food includes an abundance of bioactive compounds which are beneficial to the human organism. There are data indicating a negative relationship between sufficient vegetable and fruit intake and cancer incidence. What is more, laboratory studies confirm‎ this inverse association. It has been found that the risk of cancer incidence is half for people who eat at least five servings of fruits and vegetables per day [910, 1144, 12

Green tea polyphenols - 녹차의 폴리페놀

Next to water, tea is the most widely consumed beverage in the world. It was estimated that mean consumption of tea per day is around 120 ml per person [15Camellia sinensis, which is exposed to different processing methods before consumption. To obtain black tea the leaves of Camellia sinensis are fermented for a long period of time, which leads to formation of polymeric compounds, i.e. theaflavins and thearubigins. Oolong tea, often called half fermented, due to shorter fermentation time, contains polymeric as well as monomeric polyphenols. Non- fermented green tea is made from fresh tea leaves exposed to steaming and drying (to eliminate the oxidation process by inactivating the polyphenol oxidase) and contains an abundance of polyphenols naturally occurring in Camellia sinensis [14, 151313, 16–18], cardiovascular heart disease (coronary heart disease, hypertension, atherosclerosis) [19], Parkinson disease [20], and Alzheimer disease [2122, 23] and bone health [2414, 15

- 물 다음으로 차는 전세계에서 가장 많이 소비되는 음료임. 

- 발효하지 않은 녹차는 폴리페놀이 풍부하여 심장혈관질환, 파킨슨병, 알츠하이머, 당뇨병에 효과적임. 

The positive health effect of green tea is mostly associated with the abundance of polyphenols, particularly flavonoids. Catechins (flavan-3-ols) make up a major group of flavonoids present in green tea leaves, including epicatechin (EC), epicatechin-3-gallate (ECG), gallocatechin (GC), epigallocatechin (EGC) and predominant (-)-epigallocatechin-3-gallate (EGCG), which constitute approximately 60% of total catechins. Widely studied medical implications are mainly attributed to epi-catechins [14, 152514, 15, 26

- 녹차의 건강증진효과는 폴리페놀(특히 플라보노이드)과 주로 연관되어 있음.

- 카테킨은(flavan-3-ols)은 녹차에 들어있는  플라보노이드의 대표성분임. 

Antioxidant activity

Green tea polyphenols are responsible for significant and widely studied antioxidant properties of this beverage. Together with reactive oxygen and nitrogen species’ scavenging ability, they exert beneficial effects on the human organism, protecting against harmful cigarette smoke, pollution or stress as well as cancer development [26 Camellia sinensis show higher antioxidant potential than generally known antioxidants, vitamin E and C [14, 2714, 271315

- 녹차는 강력한 항산화효과와 비타민 E, C가 풍부함. 

Anticancer activity - 녹차의 항암효과

Green tea polyphenols were shown to reduce the risk of a multitude of cancer types (see above). It is still not clear if the influence of green tea catechins on many molecular targets is attributed to their antioxidant activity or they directly and independently affect these cell signaling pathways [14Camellia sinensis may act through stimulation of apoptosis in cancer cells, both by inactivating anti-apoptotic (Bcl-2, Bcl-Xl) and up-regulating pro-apoptotic (Bax, Bak, Bim, PUMA) proteins. Induced caspase-3 and -9 activities have also been shown [16, 29, 3014, 16, 3116, 31

As migration and invasion play a crucial role in cancer metastasis to other tissues it is of high importance to stop these processes. It was reported that EGCG can affect the phase of tumor progression and it was attributed to direct or indirect inhibition of metalloproteinase (MMP) activity [16, 31, 32

- 녹차 폴리페놀은 각종 암위험을 줄여줌. 

- 녹차 폴리페놀은 항산화 효과와 적접적으로 세포 신호전달에 영향을 주어 암세포의 apoptosis를 자극함. 

- 암세포는 전이와 침윤이 특성이므로 이러한 진행과정을 멈추는 것이 중요함. 

- 녹차의 EGCG(epigallocatechin-3-gallate)는 암세포 전이에 영향을 미치고 직접적으로  metalloproteinase (MMP) activity 를 억제함. 

참고( 클릭클릭)

Antiangiogenic activity - 녹차의 EGCG는 암세포의 혈관신생을 억제하는 효과를 보임. 

Creation of new blood vessels from pre-existing ones inside a tumor, called angiogenesis, promotes cancer development through its nourishment and oxygenation. Besides inhibiting activity of metalloproteinases which are involved in angiogenesis, EGCG was revealed to affect vascular endothelial growth factor (VEGF) binding ability to its receptor. VEGF is closely related to tumor-induced angiogenesis, acting as a mitogen factor for endothelial cells [16, 31, 3334

Polyunsaturated fatty acids (PUFAs) - 다불포화지방산

A multitude of epidemiological studies have indicated an association between polyunsaturated fatty acid consumption and cancer risk, especially breast, prostate and colon cancer [35–37in vitro and animal studies [38–4142437, 43, 4445

Although diet rich in dietary fat is often linked with increased risk of cancer, especially hormone-dependent cancer incidence, the types of consumed fatty acids have a significant impact. A preventive effect of n-3 PUFAs and cancer stimulating effect of n-6 PUFAs is suggested [457

- 많은 연구를 보면 다불포화지방산과 암(유방암, 직장암)과의 연관성이 있음.

- 일반적으로 지방이 많은 음식은 암 발생율을 높임. 특히 호르몬 의존성 암발생율..

-  preventive effect of n-3 PUFAs and cancer stimulating effect of n-6 PUFAs 가 제안됨. 

Chemopreventive activity of n-3 PUFAs

Dietary PUFAs exert a suppressing (n-3) or promoting (n-6) effect on cancer mainly through their derivatives, eicosanoids, hormone-like lipids. Prostaglandins (PG), thromboxanes (TX) and leukotrienes (LT) are synthesized in enzymatic reactions with use of cyclooxygenases (COX) and lipoxygenases (LOX). The n-3 and n-6 long chain fatty acids compete for the enzymes and eicosanoids derived from them reveal opposing effects on cell proliferation, differentiation, angiogenesis, metastasis and inflammatory responses [32, 454742, 43 It was revealed that PUFAs and their derivatives may influence several molecular signaling pathways involved in basic processes including cell growth, differentiation, apoptosis or metastasis. The n-3 PUFAs were found to down regulate protein kinase C and ras [48, 49], ERK1/2 [50], NFκB [51525342, 54, 55

- 음식으로 섭취하는 다불포화지방산은  그들의 유도물, eicosanoids, 호르몬유사 lipids를 통해 n-3 PUFAs는 암세포 억제, n-6 PUFAs는 촉진효과를 냄. 

- 프로스타글란딘, 트롬복산, 류코트리엔은 COX와 LOX의 사용으로 만들어짐. 

- n-3 and n-6 long chain fatty acids 는 암세포의 증식, 분화, 혈관신생, 전이, 염증반응을 억제함. 

Glucosinolates/isothiocyanates(글루코시놀레이트, 이소티오시안염)

Crucifers (the plant family Cruciferae, also known as Brassicaceae) include several widely consumed vegetables, e.g. cabbage, broccoli, cauliflower, parsnip, Brussels sprouts, radish, horseradish, turnip and kale [5656, 57585960615856, 59

- 십자화과 식물(양배추, 브로콜리, 콜리플라워, 무, 고추냉이, 케일)

Several mechanisms of cancer protection by glucosinolates/isothiocyanates have been proposed. The most studied is the influence of the compounds on detoxification pathways leading to increased activity of phase I and phase II enzymes and resulting in lowered amounts of carcinogens within the body due to their decreased formation as well as increased excretion. Moreover, altered activity of the enzymes was reported in vitro and in vivo [62581S or G2M arrest depending on cell type [636465

- 글루코시놀레이트, 이소티오시안염은 항암물질임. 

- 해독작용에 영향을 주고 phase 1, 2 효소의 활성증가, 몸에서 배출을 촉진하여 발암물질의 양을 낮춤. 

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Carotenoids

Among other phytochemicals present in food, carotenoids constitute a wide group of approximately 600 compounds found in almost all colored vegetables, while around 40 of them are present in daily diet. However, only 21 carotenoids are found in human serum/plasma due to differences in their bioavailability and absorption in the gut. The most commonly studied are lycopene (watermelon, tomatoes – well absorbed from tomato juice and sauce, red grapefruit, briar), β-carotene (carrots, leafy greens), lutein (dihydroxy form of α-carotene, present in kale, spinach, mango, and oranges) and zeaxanthin (dihydroxy form of β-carotene, present in corn). Since high consumption of fruits and vegetables is associated with decreased cancer risk, carotenoids are being extensively investigated for anticarcinogenic activity [66–68

At first, the cancer preventing effects were linked mainly to the precursors of vitamin A, then non-provitamin A carotenoids were also found to act as anticarcinogens [697069, 710/G1 [72] or G1/S [73692, 747576

- 라이코펜은 토마토, 수박에 많음. 

- 루테인(알파 카로틴의 dihydroxyl형태)은 케일, 시금치, 망고, 오렌지에 많음. 

- zeaxanthin(베타 카로틴의 dihydroxiy형태)는 옥수수에 많음. 

- 고농도의 과일, 야채 섭취는 암위험성을 줄이고 카로티노이드(라이코펜, 루테인, 지싼틴 등) 항암효과를 나타냄. 

- 결국 비타민 A의 전구물질로 작용하여 카로티노이드는 항암효과를 보임. 

Vitamins and minerals

Intake of minerals and vitamins in daily diet is essential for health maintenance. Although they are present in trace amounts within tissues, they play a significant role in a variety of biological processes. Some of them also have a positive impact on the process of carcinogenesis. Anticancer activity of vitamins E and C was observed, mostly due to their antioxidant effects. The protective influence of vitamin C is revealed in relation to e.g. gastric cancer through inhibiting formation of N-nitroso compounds. Besides the reactive oxygen species moderating effect, vitamin E may also induce cancer cell differentiation and apoptosis. Vitamin D and folic acid were also observed to have an impact on carcinogenesis [3

- 비타민 E, C는 항산화효과 때문에 항암효과가 있음. 

- 비타민 D, 엽산은 마찬가지로 항암효과가 있음. 

Vitamin D

Vitamin D is a fat-soluble prohormone naturally occurring in very small amounts in food. Two forms of this vitamin can be distinguished: calciferol (D2) and cholecalciferol (D3), which is produced in skin after exposure to UV-B light. Active forms of vitamin D are obtained in the body after their conversion in the liver to calcidiol (25-hydroxyvitamin D) and in kidneys to calcitriol (1, 25-dihydroxyvitamin D) [777879–848577, 8687

Folate

Folic acid (also known as vitamin B9) is a constituent found in large amounts in green leafy vegetables and fresh fruits. It plays a crucial role in proper cell division and growth and takes part in nucleotide biosynthesis [1088, 893, 1010, 90

Selenium

A variety of in vitro, animal and epidemiological studies suggest a preventive role of selenium against human cancer development, especially tumors of the gastrointestinal tract. Low levels of selenium in serum were associated with increased risk of prostate cancer. It is suggested that selenium may inhibit initiation and promotion phases of carcinogenesis [109192] as well as inhibition of cell proliferation involving alternations in MAPK kinases and Akt kinase signaling pathways [9394–9658, 97

Calcium

Calcium constitutes an essential macroelement for human health. Dairy products (milk, yogurts, and cheese), dark green vegetables, legumes and nuts constitute a good source of this micronutrient. Although some results are inconsistent, a number of epidemiological studies have attributed calcium intake with decreased colon adenoma and cancer [90, 9886, 87, 99, 100

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Conclusion

Based on various studies outlined in this review reporting a broad spectrum of naturally occurring compounds with chemopreventive activity, intense consideration of them as potential therapeutics is quite intelligible. Some of these may be already found as extracts or pure substances available for daily supplementation and are becoming a common dietary habit. However, providing a well-balanced diet containing an abundance of biologically active compounds should become a daily habit.

The authors declare no conflict of interest.

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