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Vitamin D and cancer. Ali MM, Vaidya V. J Cancer Res Ther. 2007 Oct-Dec;3(4):225-30. Review. PMID: 18270398 DOI: 10.4103/0973-1482.38998

Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells. Mantena SK, Sharma SD, Katiyar SK. Mol Cancer Ther. 2006 Feb;5(2):296-308. PMID: 16505103 doi: 10.1158/1535-7163.MCT-05-0448 The effectiveness of berberine in checking the growth of androgen-insensitive, as well as androgen-sensitive, prostate cancer cells without affecting the growth of normal prostate epithelial cells indicates that it may be a promising candidate for prostate cancer therapy. The evaluation of ancient herbal medicines may indicate novel strategies for the treatment of prostate cancer, which remains the leading cause of cancer-related deaths in American men (1). In our present investigation, we show that a naturally occurring isoquinoline alkaloid, berberine, significantly inhibits the proliferation and reduces the viability of DU145 and PC-3 as well as LNCaP cells (Fig. 1), which suggests that berberine may be an effective chemotherapeutic agent against both androgen-sensitive and androgen-insensitive prostate cancer cells. Importantly, we found that berberine did not exhibit toxicity to nonneoplastic human prostate epithelial cells under the conditions used, except for a moderate reduction in cell viability at higher concentrations when cells were treated in vitro for an extended period of time. In conclusion, the results of the present study indicate that berberine inhibits proliferation and induces G1-phase arrest and apoptosis in human prostate cancer cells but not in normal human prostate epithelial cells. In addition, we provide mechanistic evidence that berberine-induced apoptosis in prostate carcinoma cells, particularly hormone-refractory prostate carcinoma cells, is mediated through enhanced expression of Bax, disruption of the mitochondrial membrane potential, and activation of caspase-3.

Yang P, Cartwright C, Chan D, Vijjeswarapu M, Ding J, Newman RA. Zyflamend((R))-Mediated Inhibition of Human Prostate Cancer PC3 Cell Proliferation: Effects on 12-LOX and Rb Protein Phosphorylation. Cancer Biol Ther. 2007 Feb 25;6(2) [Epub ahead of pr

Yeudall WA, Miyazaki H. Chemokines and squamous cancer of the head and neck: targets for therapeutic intervention? Expert Rev Anticancer Ther. 2007 Mar;7(3):351-60. PMID: 17338654 [PubMed - in process]

Schroeder CP, Yang P, Newman RA, Lotan R. Eicosanoid metabolism in squamous cell carcinoma cell lines derived from primary and metastatic head and neck cancer and its modulation by celecoxib. Cancer Biol Ther. 2004 Sep;3(9):847-52. Epub 2004 Sep 18. P

M. F. McCarty and K. I. Block Toward a core nutraceutical program for cancer management. Integr Cancer Ther, June 1, 2006; 5(2): 150 - 171.

Brewer GJ, Merajver SD. Cancer therapy with tetrathiomolybdate: antiangiogenesis by lowering body copper--a review. Integr Cancer Ther. 2002 Dec;1(4):327-37. Review. PMID: 14664727 [PubMed - indexed for MEDLINE]

Pan Q, Bao LW, Kleer CG, Brewer GJ, Merajver SD. Antiangiogenic tetrathiomolybdate enhances the efficacy of doxorubicin against breast carcinoma. Mol Cancer Ther. 2003 Jul;2(7):617-22. PMID: 12883034 [PubMed - indexed for MEDLINE]

Meta-analysis: longitudinal studies of serum vitamin D and colorectal cancer risk. Yin L, Grandi N, Raum E, Haug U, Arndt V, Brenner H. Aliment Pharmacol Ther. 2009 Jul 1;30(2):113-25. Epub 2009 Apr 15. PMID: 19392870 DOI: 10.1111/j.1365-2036.2009.04022.x Conclusions Our results support suggestions that serum 25(OH)D is inversely related to CRC risk.

Mitochondrially targeted effects of berberine [Natural Yellow 18, 5,6-dihydro-9,10-dimethoxybenzo(g)-1,3-benzodioxolo(5,6-a) quinolizinium] on K1735-M2 mouse melanoma cells: comparison with direct effects on isolated mitochondrial fractions. Pereira GC, Branco AF, Matos JA, Pereira SL, Parke D, Perkins EL, Serafim TL, Sardão VA, Santos MS, Moreno AJ, Holy J, Oliveira PJ. J Pharmacol Exp Ther. 2007 Nov;323(2):636-49. Epub 2007 Aug 17. PMID: 17704354 doi: 10.1124/jpet.107.128017 The present work shows that berberine is accumulated by mitochondria of a mouse melanoma cell line, leading to mitochondrial fragmentation and dysfunction, accompanied by decreased cellular energy charge. When the effect was compared with the results obtained on isolated mitochondrial fractions, it is observed that regardless of the system used, berberine is toxic for mitochondria. One major limitation of the present study (as in many others) is the lack of knowledge of the real concentration of berberine that reaches mitochondria in intact cells. Although we do not possess data regarding this aspect, it is wise to speculate that mitochondrial berberine concentrations will be much higher than in the bulk cytosol due to electrophoretic accumulation. We believe that the range of berberine concentrations accumulated by mitochondria in intact cells is within the range of concentrations used on isolated mitochondrial fractions in the present study. The present work not only provides insights on the mechanism by which berberine interferes with tumor cell proliferation, demonstrating previously unknown effects on mitochondrial physiology, but also raises a note of caution on the use of berberine as a nontoxic "natural" over-the-counter medication.

Tetrathiomolybdate promotes tumor necrosis and prevents distant metastases by suppressing angiogenesis in head and neck cancer -- Hassouneh et al. 6 (3): 1039 -- Molecular Cancer Therapeutics