Natural treatment for advanced prostate cancer, Part 3

July 30, 2012, Featured in Cancer and Natural Medicines, 0 Comments

Zinc is necessary for the production of testosterone and inhibiting the enzymatic activity of prostate specific antigen (PSA), a marker for the diagnosis and monitoring of prostate cancer. PSA is a protein produced by cells of the prostate gland. PSA is specific to the prostate and is not cancer-specific. Therefore elevated levels of PSA is seen in an array of condition such as prostatitis (inflammation of the prostate) and benign hypertrophy of the prostate (enlargement of the prostate) besides prostate cancer.

PSA could play a role in prostate cancer cell growth, migration and invasion. PSA is a serine protease with a molecular weight of approximately 33 kDa. The serine proteases are a family of enzymes that cut certain peptide bonds in other proteins. In mammals, serine proteases perform many important functions, especially in digestion, blood clotting, and the complement system. The serine protease activity of PSA could be involved in the invasion and metastasis of prostate cancer.

PSA is actually an enzyme that digests semen proteins called semenogelin I and II, resulting in liquefaction and the release of motile spermatozoa. The prostate is surrounded by a thin layer of connective tissue that merges with surrounding soft tissues, including nerves. If PSA synthesis, controlled by androgens, becomes excessive, PSA can digest the connective tissue in the prostate. Cancer metastasis is accompanied by degradation of connective tissue necessary to facilitate the spread and invasion of cancer cells from one organ to other parts of the body.

This means, if prostate cancer cells already exist in the body, PSA can definitely contribute to their growth and their invasion, or their metastatic capability. PSA degrades extracellular matrix glycoproteins fibronectin and laminin and, thus, may facilitate invasion by prostate cancer cells. The extracellular matrix degrading ability of PSA not only makes it a marker for early detection but also a target for prevention and intervention in prostate cancer. Zinc ions have a strong inhibitory effect on the activity of PSA. Zinc ions in human prostate suppress the invasion and metastasis of prostate cancer cells through the regulation of the proteolytic activity of PSA. Simply put, zinc inhibits the growth of these highly metastatic prostate cancer cells.

Prostate-specific antigen is a “chymotrypsin-like” serine protease with unique P1 substrate specificity.

Prostate-specific antigen: an overlooked candidate for the targeted treatment and selective imaging of prostate cancer.

Presence and enzymatic activity of prostate-specific antigen in archival prostate cancer samples.

Semenogelins I and II bind zinc and regulate the activity of prostate-specific antigen.

Prostate-specific antigen, a serine protease, facilitates human prostate cancer cell invasion.

PSA affects prostate cancer cell invasion in vitro and induces an osteoblastic phenotype in bone in vivo.

Enzymatic action of prostate-specific antigen (PSA or hK3): substrate specificity and regulation by Zn(2+), a tight-binding inhibitor.

Evidence that the prostate-specific antigen (PSA)/Zn2+ axis may play a role in human prostate cancer cell invasion.

Telomeres are guanine-rich repeated sequences located at the ends of chromosomes. However, each time a cell divides, some of the telomere is lost. The loss of telomeric repeats after each cell division may function as a biological clock limiting the cell proliferation ability.When the telomere becomes too short, the chromosome reaches a “critical length” and can no longer replicate. This means that a cell becomes “old” and dies by an apoptotic process.

Telomerase is an enzyme that rescues cells from destruction by extending the protective caps on the ends of chromosomes. If telomerase is activated in a cell, the cell will continue to grow and divide. Cancer cells have very short telomeres. The only thing keeping these cells alive is their overexpression of the enzyme telomerase. Telomerase is expressed in more than 85% of cancer cells, making it a nearly universal cancer marker, while the majority of normal somatic cells are telomerase negative. In mice, reactivating telomerase led to the repair of damaged tissues and reversed the signs of ageing.

In most advanced cancers, telomerase is reactivated and serves to maintain telomere length and emerging data have also documented the capacity of telomerase to directly regulate cancer-promoting pathways. The mechanism for the activation of telomerase in cancer cells, however, is still unclear. Therefore, suppression of telomerase activity is a universal cancer therapeutic target. Unfortunately, zinc enhances the activity of telomerase.

Indole-3-carbinol (I3C) is a phytochemical with anticarcinogenic properties derived from the cruciferous vegetables of the Brassica genus (cabbage, broccoli, cauliflower and brussels sprouts). I3C initiates a series of reactions in the body that culminates in the elimination of estrogen. In the liver, I3C promotes the metabolism of estrogen and increases the ratio of 2-hydroxy estrogen to 16-hydroxy estrogen. The 2-hydroxy estrogens, less active than the 16-hydroxy estrogens, generally are eliminated more rapidly from the body. I3C can help to maintain healthy hormonal balance for both men and women and therefore may support the health of the breast, prostate, and other reproductive organs.

I3C is acid-catalyzed in the stomach into diindolylmethane (DIM). The majority of ingested I3C is absorbed in the small intestine as DIM, which is believed to be the active beneficial constituent in I3C and cruciferous vegetables. DIM has been shown to selectively bind to estrogen receptors and may act as an estrogen antagonist at physiological concentration. Both I3C and DIM induce biochemical pathways to metabolize potential carcinogens. Research shows that DIM inhibits dihydyrotestosterone (DHT) from binding to androgen receptors in androgen-dependent human prostate cancer cells, decreasing the induction of DNA synthesis.

I3C was first investigated for its potential role in preventing breast cancer and benefiting patients infected with the human papilloma virus. New research, however, continues to reveal that this cruciferous vegetable-derived nutrient can inhibit numerous forms of cancer including breast cancer, prostate cancer, endometrial cancer, colon cancer, and leukemia. I3C is a potent inhibitor of the synthesis and activation of telomerase enzymes. I3C also inhibits production of PSA in the prostate cancer cells. Recent studies continue to confirm that I3C inhibits cancer cell growth and prevents cancer cell division by blocking DNA duplication. Furthermore, in cancer cells, it triggers apoptosis (cell death).

I3C is available without a prescription as a dietary supplement. When used for prostate cancer treatment, the dosage used has been up to 800mg per day. The usual dosage for men is 400 mg per day taken with food. ProstaZym contains I3C / DIM complex and its perfectly enhanced bioavailability delivery system for I3C / DIM complex.The bioavailability of ProstaZym is superior to regular DIM and its unstable precursor, indole-3 carbinol (l3C). With ProstaZym you are assured a stabilized dose and consistent benefit.

ProstaZym also contains phenethyl isothiocyanate (PEITC), a bioactive constituent of many edible cruciferous vegetables. The mechanisms behind the anticancer effects of PEITC are not fully understood. Studies have indicated that PEITC mediates gene regulation, such as downregulation of androgen receptor expression and induction of endogenous cyclin-dependent kinase inhibitors, p21 and p27. The gene for detoxifying enzyme pi-class glutathione S-transferase (GSTP1), silenced in the vast majority of prostate tumor cells, could be reactivated and the enzymatic function recovered. Dietary PEITC suppress prostate cancer progression by induction of autophagic cell death, another important physiological cell death process.

Is telomerase a viable target in cancer?

Prostate tumor cells with cancer progenitor properties have high telomerase activity and are rapidly killed by telomerase interference.

Telomerase reactivation following telomere dysfunction yields murine prostate tumors with bone metastases.

The effects of telomerase inhibition on prostate tumor-initiating cells.

Modulation of telomerase activity by zinc in human prostatic and renal cancer cells.

Indole-3-carbinol inhibits telomerase activity and gene expression in prostate cancer cell lines

Indole-3-carbinol induces a G1 cell cycle arrest and inhibits prostate-specific antigen production in human LNCaP prostate carcinoma cells.

Plant-derived 3,3′-Diindolylmethane is a strong androgen antagonist in human prostate cancer cells.

Chemopreventative potential of the cruciferous vegetable constituent phenethyl isothiocyanate in a mouse model of prostate cancer.

Prostate cancer chemopreventive activity of phenethyl isothiocyanate through epigenetic regulation (review).

Atg5 regulates phenethyl isothiocyanate-induced autophagic and apoptotic cell death in human prostate cancer cells.

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