Lycopene and Cancer

Lycopene is a non-provitamin A carotenoid that gives tomatoes their red color. Non-provitamin A properties means that it is a carotenoid that the body cannot convert into Vitamin A, whereas beta-carotene and some other carotenoids found in nature, can be converted by the body into Vitamin A, if the body needs the extra Vitamin A.

Humans and animals do not synthesize lycopene, and thus rely on food sources. Other sources of lycopene include tomato products (tomato sauce, tomato juice), watermelon, pink grapefruit, apricots, pink guava and papaya. Lycopene is a potent antioxidant and quenches singlet oxygen and may modulate mutagenesis, carcinogenesis, cell differentiation and proliferation, according to experimental evidence. More specifically, experimental evidence suggests that lycopene may be beneficial to prevent cancer and in adjunctive cancer management in that it has been shown to:

  1. Inhibit replication of cancer cells via its influence on cell cycle regulatory proteins.
  2. Induce cellular differentiation of cancer cells, helping to control their malignant behavior
  3. Modulate the IGF-1/IGFBP-3 system, which induces apoptosis via its effects on transforming growth factor-beta-1 and p53 tumor suppressor gene activity. In the human body 97-99% of IGF-1 is bound to one of six IGF binding proteins (IGFBP).

IGFBP-3 is the most abundant of these binding proteins, accounting for approximately 80% of IGF-1 binding. Induction of IGF-BP3 gene expression by lycopene is associated with enhanced secretion of an active form of IGF-BP3 capable of inhibiting mitogenic signaling by the insulin-like growth factor IGF-1. This helps to inhibit replication of cancer cells, as many cancer cells rely on IGF-1 signaling stimulation to up-regulate their the cell division activity.

Other results indicate that IGF-BP3 up-regulates the p53 tumor suppressor gene thereby, inducing apoptosis of cancer cells and other damaged or infected cells

  1. Induce up-regulation of gap junction communication between adjacent cells (via gap-junctional gene connexin 43 (Cx43).
  2. Affect modulation of redox signaling (antioxidant function), as free radical levels augment synthesis of 5 and 12 lipoxygenase enzymes, as well as cyclo-oxygenase enzyme, which affect the cellular proliferation rate.
  3. Inhibit inteukin-6 and androgens
  4. Inhibit the 5-lipoxygenase enzyme
  5. Modulate carcinogen metabolizing enzymes (increased detoxification at the cellular level)
  6. Modulate immune function

Human Prostate Clinical Trial Using Lycopene

Dietary intake of lycopene and soy have been associated with a lower risk of prostate cancer. In vitro studies with lycopene and genistein, a soy isoflavone, have shown induction of apoptosis and inhibition of cell growth in androgen-sensitive (LNCaP) and androgen–independent (PC3 and VeCaP) prostate cancer cell lines.

            In a Phase II clinical trial (Vaishampayan U et al, 2007) researchers investigated the efficacy of lycopene alone, or in combination with soy isoflavones, on serum PSA levels in men with prostate cancer. To be eligible for the study men with prostate cancer had to have rising serum PSA following local therapy or while on hormone therapy. The study population included 71 patients who had 3 successive rising PSA levels, or a minimum PSA of 10 ng/ml at 2 successive evaluations prior to starting therapy.

            Subjects were randomly assigned to receive a tomato extract capsule containing 15 mg of lycopene alone (n = 38) or together with a capsule containing 40 mg of a soy isoflavone mixture (n = 33), twice daily orally for a maximum of 6 months. One patient on the lycopene arm did not receive therapy due to his inability to ingest the study pill.

            There was no decline in serum PSA in either group. However, 35 of 37 (95%) patients in the lycopene group and 22 of 33 (67%) patients in the lycopene plus soy isoflavone group achieved stable disease, meaning that they achieved stabilization in serum PSA level. The data suggest that lycopene and soy isoflavones have important adjunctive effects in prostate cancer patients with PSA relapse disease, and may delay progression of both hormone-refractory and hormone-sensitive prostate cancer.

 

Reference:

Vaishampayan U, Hussain M, Seren S, Sarkar F, Fontana J et al. Lycopene and Soy Isoflavones in the Treatment of Prostate Cancer.Nutri and Cancer. 2007; 59 (1): 1-7

 

 

Additional Information Regarding Lycopene And Cancer

Lycopene represents as much as 50% of the carotenoids found in human serum. Lycopene demonstrates a high level of bioavailability, which is enhanced when tomatoes and other lycopene-containing vegetables and fruits are heated, chopped and processed. This explains why tomato sauce is such a good and bioavailable source of lycopene.

Lycopene has been shown to concentrate in the prostate gland, adrenals, testes, skin, liver and kidneys. The body cannot convert lycopene into Vitamin A, as it can with some other carotenoids (e.g. beta-carotene), but lycopene demonstrates powerful antioxidant activity and is the most effective quencher of oxygen free radicals among the many carotenoids found in nature, being twice as potent as beta-carotene in this regard.

Under experimental conditions lycopene is able to reduce lung adenomas and carcinomas, colon cancer, prostate cancer, breast (mammary) tumor, and to inhibit endometrial cancer as well as HL-60 leukemic cell growth.

Epidemiological evidence indicates that the ingestion of tomato products is associated with a reduction in risk of overall cancer mortality or incidence. The evidence appear to be strongest for reduced risk of pancreatic, rectal, colon, esophageal, oral, cervical, breast and prostate cancer. The Mediterranean-type diet in particular, which has a higher intake of tomato products, is associated with lower incidence of digestive tract cancers.

 

Reference:

Fazekas Z, Gao D, Saladi RN et al. Protective effects of lycopene against ultraviolet B-induced photodamage. Nutr and Cancer 2003, 47;2: 181-187

 

 

Prostate Cancer

Lycopene intake of 6.5 mg per day has been linked to a 21% decreased risk of prostate cancer compared with those consuming the least.  This study also reported that those who ate more than ten servings per week of tomato-based foods had a 35% decreased risk of prostate cancer compared with those eating less than 1.5 weekly servings.1

Lycopene is the most abundant carotenoid in the prostate2, and high blood levels of Lycopene have been linked to prostate cancer prevention,3 including prospective or longitudinal studies.4

Women’s Health

Higher intakes of Lycopene have also been associated with a lower risk of cervical intraepithelial neoplasia – precancerous changes of the cervix and cervical dysplasia.5-8 Some preliminary evidence also suggests that Lycopene may help reduce the risk of breast cancer.9

Immune System

Lycopene supplementation has also boosted immune function in the elderly (15 mg of Lycopene per day increased natural killer cell activity by 28% in twelve weeks) 9

 

References:

  1. Giovannucci E, Ascherio A, Rimm EB, et al. Intake of carotenoids and retinal in relation to risk of prostate cancer.  J Natl Cancer Inst 1995;87:1767-76.
  2. Carter HB, Coffey DS.  The prostate: an increasing medical problem.  Prostate 1990;16:39-48.
  3. Hsing AW, Comstock GW, Abbey H, Polk F.  Serologic precursors of cancer.  Retinol, carotenoids, and tocopherol and risk of prostrate cancer.  J Natl Cancer Inst 1990;82:941-6.
  4. Gann PH, Ma J, Giovannucci E, Willett W, Sacks FM, Hennekens CH, et al .  Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis (physicians health study).  Cancer Res 1999;59(6):1225-30.
  5. Van Eenwyk J, Davis FG,BownePE.  Dietary and serum carotenoids and cervical intraepithelial neoplasia.  Int J Cancer 1991;48:34-38.
  6. Kanetsky PA, Gammon MD, Mandelblatt J, Zhang ZF, Ramsey E, Dnistrian A, et al.  Dietary intake and blood levels of lycopene: an association with cervical dysplasia among non-hispanic, black women.  Nutr Cancer 1998;31:31-40.
  7. Cuzik J, Stavola BL, Russell MJ, Thomas BS.  Vitamin A, Vitamin E and risk of cervical intraepithelial neoplasia.  Br J Cancer 1990;62:651-2.
  8. La Vecchia C, Decarli A, Fasoli M, Parazzini F, Franceschi S, Gentile A, et al.  Dietary Vitamin A and the risk of intraepithelial and invasive cervical neoplasia.  Gynegol Oncol 1988;30:187-95.
  9. Corridan BM, O'Donohue MP, Morrissey PA.  Carotenoids and immune response in elderly people.  Proc Nutr Soc 1998;3(Abstract):57A.

 

 

 

 

 

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