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Cancer; natural, complementary treatments
Natural Compounds Show Antiangiogenic Activity
Charles Marwick
Ever since evidence emerged that growth of malignant tumors could be slowed or even prevented by cutting off their blood supply, the search for antiangiogenic agents has widened and now includes natural compounds and compounds derived from natural agents. "There are easily 4 dozen natural compounds that are antiangiogenic," said Raymond Chang, M.D., medical director of Meridian Medical Group, New York, and clinical assistant professor of medicine at the Albert Einstein School of Medicine, N.Y. "The field is complex and it’s important to realize this. There is no magic bullet here. There is no single answer, no single pathway," he warned.
At the recent fourth annual conference on Integrating Complementary and Alternative Therapies in Cancer in Arlington, Va., Chang reviewed a number of studies involving various natural compounds and extracts of natural compounds that have shown some antiangiogenic activity.
They include shark cartilage, curcumin (the yellow pigment in tumeric), the omega-3 and omega-6 fatty acids, green tea, licorice, quercetin (a bioflavonoid present in fruits and vegetables), squalamine (an extract of dogfish liver), and vitamin D3.
Some of these agents are in clinical trials. For instance, one form of shark cartilage extract, Neovastat, is being developed by Aeterna Laboratories, Quebec, Canada. It is in early phase III trials for the management of renal cell carcinoma, non-small-cell lung cancer, and prostate cancer. Another agent is squalamine, which is in phase II trials, sponsored by Genaera Laboratories, Plymouth Meeting, Pa., for the treatment of some solid tumors and lung and ovarian cancers.
Vitamin D and cancer.
Ali MM, Vaidya V. J Cancer Res Ther. 2007 Oct-Dec;3(4):225-30. Links
Department of Microbiology, Institute of Science, 15, Madame Cama Road, Mumbai-400 032, India. minu_ali@yahoo.co.in
Vitamin D, a fat-soluble prohormone is synthesized in response to sunlight. Experimental evidence suggests that vitamin D may reduce the risk of cancer through regulation of cellular proliferation and differentiation as well as inhibition of angiogenesis. These anticancer properties have been attributed primarily to 1,25-dihydroxyvitamin D [1,25(OH) 2 D] (calcitriol), the hormonal form of vitamin D. Extensive research has shown that cells, including cancer cells, express specific receptors (VDR) for 1,25-dihydroxyvitamin D. When bound to the VDR, 1,25-dihydroxyvitamin D regulates> 60 genes that exert prodifferentiating, antiproliferative and antimetastatic effects on cells, including effects on cell cycle. The amount of exposure to the sun has been found to correlate inversely with cancer mortality and survival in numerous epidemiological studies. An inverse relationship between solar ultraviolet-B (UV-B) exposure and non-skin cancer mortality has long been reported. Several ecological studies suggest that sunlight may protect against prostate, colon, rectal, female breast and ovarian cancer, all diseases that contribute to a substantially higher proportion of cancer mortality in the western industrialized world. Some analytical studies also suggest a protective association between circulating vitamin D in blood, which is largely derived from sunlight, or dietary vitamin D. Paricalcitol (calcitriol analogue) is as effective as 1,25-dihydroxyvitamin D in transactivating the prostatic VDR and in inhibiting the growth of prostate cancer cell lines and primary cultures of prostate cancer cells in vitro. Promising preclinical evaluations of calcitriol and analogues have appeared in prostate cancer animal models.
Shedding light on vitamin D and integrative oncology.
Integr Cancer Ther. 2008 Jun;7(2):81-9. Epub 2008 May 27.
Cantor I. Steiner Medical and Therapeutic Center, Phoenixville, Pennsylvania 19460, USA. isc@steinermed.com
Studies show an important relationship between vitamin D and malignancies, both in prevention and treatment. The extraskeletal actions of vitamin D relevant to oncology include being proapoptotic, antimetastatic, antiangiogenic, antiinflammatory, prodifferentiating, and immunomodulating. Widespread and severe vitamin D deficiencies exist worldwide. Decreased sun exposure, caused by lifestyle changes, as well as fear of skin cancers, is the main cause of these deficiencies. Recommended daily oral intakes, as well as suggested blood levels, are below optimal levels suggested by studies. Improvement in vitamin D status, through lifestyle changes and supplementation, can be of profound benefit regarding the occurrence and mortality of malignancies.
The influence of isoflavonoids on the antitumor activity of vitamin D3; good help for Cancer treatments?
Postepy Hig Med Dosw (Online). 2007;61:253-60 Wietrzyk J.
Laboratorium Doświadczalnej Terapii Przeciwnowotworowej Instytutu Immunologii i Terapii Doświadczalnej PAN im. L. Hirszfelda we Wrocławiu, Poland. wietrzyk@iitd.pan.wroc.pl
Isoflavonoids exert a regulatory function on the expression of cytochrome P450 enzymes and also up-regulate the vitamin D(3) receptor (VDR) on cancer cells, which increase their sensitivity to 1,25-dihydroxyvitamin D(3) , the hormonally active form of vitamin D(3) . Isoflavonoids (like resveratrol) are also able to raise the serum level of the active form of vitamin D(3) due to their inhibitory activity on CYP24, the enzyme involved in the degradation of 1,25-dihydroxyvitamin D(3) and its precursor 25-OH-D(3) to inactive compounds. Another enzyme, CYP27B1, involved in the synthesis of 1,25-dihydroxyvitamin D(3) , is stimulated by isoflavonoids, and this may result in a similar effect of increasing in the serum level of 1,25-dihydroxyvitamin D3. CYP27B1 and CYP24 were found in kidneys (the main location of 1,25-(OH) (2)D(3) synthesis) and also in brain cells, osteoclasts, keratinocytes, macrophages, intestine epithelial cells, and in some cancer cells. The expression of VDR was detected not only in the cells primarily targeted by 1,25-dihydroxyvitamin D3, but also in epithelial and mesenchymal cells. Therefore, combined treatment with isoflavonoids and 1,25-dihydroxyvitamin D3 might be effective in both cancer prevention and treatment.
Bacopa monniera Linn. extract modulates antioxidant and marker enzyme status in fibrosarcoma bearing rats.
Rohini G, Sabitha KE, Devi CS. Indian J Exp Biol. 2004 Aug;42(8):776-80.Links
Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 020, India.
Antioxidative property and tumor inhibitive property of B. monniera (20mg/kg body wt, sc) was examined in 3-methylcholanthrene induced fibrosarcoma rats. Antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and the levels of glutathione (GSH) and the rate of lipid peroxidation (LPO) in the liver and kidney tissues were assessed.
Fibrosarcoma
A significant increase was noted for the rate of LPO with a corresponding decrease in the antioxidant enzyme status in fibrosarcoma bearing rats. In fibrosarcoma bearing rats, the tumor markers like lactate dehydrogenase (LDH), creatine kinase (CK), alanine transaminase (ALT), aspartate transaminase (AST) and sialic acid (SA) were increased in the serum. Treatment with B. monniera extract significantly increased the antioxidant enzyme status, inhibited lipid peroxidation and reduced the tumor markers. It can be concluded that B.monniera extract promotes the antioxidant status, reduces the rate of lipid peroxidation and the markers of tumor progression in the fibrosarcoma bearing rats.
Modulation of anti-apoptotic and survival pathways by curcumin as a strategy to induce apoptosis in cancer cells.
Reuter S, Eifes S, Dicato M, Aggarwal BB, Diederich M. Biochem Pharmacol. 2008 Aug 3.
Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9 rue Edward Steichen, L-2540 Luxembourg, Luxembourg.
Apoptosis is a highly regulated mechanism by which cells undergo cell death in an active way. As one of the most challenging tasks concerning cancer is to induce apoptosis in malignant cells, researchers increasingly focus on natural products to modulate apoptotic signaling pathways. Curcumin, a natural compound isolated from the plant Curcuma longa, has chemopreventive properties, which are mainly due to its ability to arrest cell cycle and to induce apoptosis. This article reviews the main effects of curcumin on the different apoptotic signaling pathways involved in curcumin-induced apoptosis of cancer cells, including the intrinsic and extrinsic apoptosis pathways, the NF-kappaB-mediated pathway as well as the PI3K/Akt signaling pathway. This review also focuses on the sensitization of cells to TRAIL-induced apoptosis after curcumin treatment and shows that curcumin enhances the capacity to induce cell death of different chemotherapeutical drugs.
New mechanisms and therapeutic potential of curcumin for colorectal cancer.
Villegas I, Sánchez-Fidalgo S, Alarcón de la Lastra C.
Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville, Spain. Fax: +34-9-5-4556074. Mol Nutr Food Res. 2008 Jul 24.
Curcumin is a polyphenol derived from Curcuma longa. Over the last few years, a number of studies have provided evidence of its main pharmacological properties including chemosensitizing, radiosensitizing, wound healing activities, antimicrobial, antiviral, antifungical, immunomodulatory, antioxidant and anti-inflammatory. More recent data provide interesting insights into the effect of this compound on cancer chemoprevention and chemotherapy. In fact, preclinical studies have shown its ability to inhibit carcinogenesis in various types of cancer including colorectal cancer (CRC). Curcumin has the capacity of interact with multiple molecular targets affecting the multistep process of carcinogenesis. Also, curcumin is able to arrest the cell cycle, to inhibit the inflammatory response and the oxidative stress and to induce apoptosis in cancer cells. Likewise, it has been shown to possess marked antiangiogenic properties. Furthermore, curcumin potentiates the growth inhibitory effect of cyclo-oxygenase (COX)-2 inhibitors and traditional chemotherapy agents implicating another promising therapy regimen in the future treatment of CRC. However, its clinical advance has been hindered by its short biological half-life and low bioavailability after oral administration. This review is intended to provide the reader an update of the bioavailability and pharmacokinetics of curcumin and describes the recently identified molecular pathways responsible of its anticancer potential in CRC.
Coffee consumption and the risk of cancer: An overview.
Nkondjock A. Cancer Lett. 2008 Sep 30.
Research Center for Military Health, P.O. Box 906, Yaounde, Cameroon; Yaounde Military Hospital, P.O. Box 12794, Yaounde, Cameroon.
Habitual coffee drinking has been associated with a reduced risk of mortality and chronic diseases, including cancer. The favourable influence of coffee is supported by several plausible mechanisms due to the presence of a variety of biological compounds such as caffeine, diterpenes, caffeic acid, polyphenols as well as volatile aroma and heterocyclic substances. Current evidence suggests that coffee consumption is associated with a reduced risk of liver, kidney, and to a lesser extent, premenopausal breast and colorectal cancers, while it is unrelated to prostate, pancreas and ovary cancers. Coffee drinking may still help reduce death due to liver cancer.
Health properties of shark oil
Szostak WB, Szostak-Wegierek D. Przegl Lek. 2006;63(4):223-6
Zakład Profilaktyki Chorób, Zywieniowozaleznych z Poradnia Chorób Metabolicznych, Instytut Zywności i Zywienia w Warszawie.
Fish oils are the source of nutrients important for health maintenance. The most significant are essential fatty acids (EFA) of n-3 family, alkylglycerols and squalene. N-3 EFA are of great importance in atherosclerosis prevention. Alkylglycerols and squalene are modulators of immunity to infections and cancer. Shark liver oil contains great amounts of alkylglycerols and squalene, and moderate of n-3 EFA. Therefore, it is used as an adjunctive agent in cancer therapy, especially in radiotherapy, and in the treatment of infectious diseases.
Studies:
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