Curcumin, derived from the rhizome curcuma longa, is one of the primary ingredients in turmeric and curry powders that are used as spices in Middle Eastern and Asian countries, especially on the Indian subcontinent. More recently, laboratory studies have demonstrated that dietary curcumin exhibits various biological activities and significantly inhibits colon tumorigenesis and tumor size in animals. Curcumin displays both anti-inflammatory and antioxidant properties, giving it the potential to be considered in the development of cancer preventive strategies and applications in clinical research. Experimental studies have shown the biological activities of the compound, but much more information on pharmacokinetics, bioavailability, and food content are needed. Whether the amount of curcumin in turmeric and curry powders is sufficient to suggest effects on biological activities and cancer risk is unknown. To determine and compare the quantitative amounts of curcumin that are present in several brands of turmeric and curry powders, a high performance liquid chromatography technique was used to analyze 28 spice products described as turmeric or curry powders and two negative controls. Pure turmeric powder had the highest curcumin concentration, averaging 3.14% by weight. The curry powder samples, with one exception, had relatively small amounts of curcumin present, and the variability in content was great. The curcumin content of these seasoning products that are consumed as a component of the diet should be considered in evaluating baseline tissue concentration and response to curcumin supplementation, which is under study in chemoprevention trials.
Purpose:Pancreatic cancer is almost always lethal, and the only U.S. Food and Drug Administration-approved therapies for it, gemcitabine and erlotinib, produce objective responses in <10% of patients. We evaluated the clinical biological effects of curcumin (diferuloylmethane), a plant-derived dietary ingredient with potent nuclear factor-kappaB (NF-kappaB) and tumor inhibitory properties, against advanced pancreatic cancer.
Experimental Design:Patients received 8 g curcumin by mouth daily until disease progression, with restaging every 2 months. Serum cytokine levels for interleukin (IL)-6, IL-8, IL-10, and IL-1 receptor antagonists and peripheral blood mononuclear cell expression of NF-kappaB and cyclooxygenase-2 were monitored.
Results:Twenty-five patients were enrolled, with 21 evaluable for response. Circulating curcumin was detectable as drug in glucuronide and sulfate conjugate forms, albeit at low steady-state levels, suggesting poor oral bioavailability. Two patients showed clinical biological activity. One had ongoing stable disease for >18 months; interestingly, one additional patient had a brief, but marked, tumor regression (73%) accompanied by significant increases (4- to 35-fold) in serum cytokine levels (IL-6, IL-8, IL-10, and IL-1 receptor antagonists). No toxicities were observed. Curcumin down-regulated expression of NF-kappaB, cyclooxygenase-2, and phosphorylated signal transducer and activator of transcription 3 in peripheral blood mononuclear cells from patients (most of whom had baseline levels considerably higher than those found in healthy volunteers). Whereas there was considerable interpatient variation in plasma curcumin levels, drug levels peaked at 22 to 41 ng/mL and remained relatively constant over the first 4 weeks.
Cconclusions:Oral curcumin is well tolerated and, despite its limited absorption, has biological activity in some patients with pancreatic cancer.
Curcumin, traditionally used as a seasoning spice in Indian cuisine, has been reported to decrease the proliferation potential of prostate cancer cells, by a mechanism that is not fully understood. In the current study, we have evaluated the effects of curcumin in cell growth, activation of signal transduction, and transforming activities of both androgen-dependent and independent cell lines. Prostate cancer cell lines, LNCaP and PC-3, were treated with curcumin and its effects were further analyzed on signal transduction and expression of androgen receptor (AR) and AR-related cofactors using transient transfection assay and Western blotting. Our results show that curcumin down-regulates transactivation and expression of AR, activator protein-1 (AP-1), nuclear factor-kappaB (NF-kappaB), and CREB (cAMP response element-binding protein)-binding protein (CBP). Curcumin also inhibited the transforming activities of both cell lines as evidenced by the reduced colony forming ability in soft agar. The results obtained here demonstrate that curcumin has a potential therapeutic effect on prostate cancer cells through down-regulation of AR and AR-related cofactors (AP-1, NF-kappaB and CBP).
Background:Earlier work from our laboratory highlighted the therapeutic potential of curcumin (turmeric), used as a dietary ingredient and as a natural anti-inflammatory agent in India and other Southeast Asian countries. This agent was shown to decrease the proliferative potential and induce the apoptosis potential of both androgen-dependent and androgen-independent prostate cancer cells in vitro, largely by modulating the apoptosis suppressor proteins and by interfering with the growth factor receptor signaling pathways as exemplified by the EGF-receptor. To extend these observations made in vitro and to study the efficacy of this potential anti-cancer agent in vivo, the growth of LNCaP cells as heterotopically implanted tumors in nude mice was followed.
Methods:The androgen-dependent LNCaP prostate cancer cells were grown, mixed with Matrigel and injected subcutaneously into nude mice. Experimental group received a synthetic diet containing 2% curcumin for up to 6 weeks. At the end point, sections taken from the excised tumors were evaluated for pathology, cell proliferation, apoptosis, and vascularity.
Results:Curcumin causes a marked decrease in the extent of cell proliferation as measured by the BrdU incorporation assay and a significant increase in the extent of apoptosis as measured by an in situ cell death assay. Moreover, a significant decrease in the microvessel density as measured by the CD31 antigen staining was also seen.
Conclusions:Curcumin could be a potentially therapeutic anti-cancer agent, as it significantly inhibits prostate cancer growth, as exemplified by LNCaP in vivo, and has the potential to prevent the progression of this cancer to its hormone refractory state.
Curcumin I (Cur I) and curcumin III (Cur III) are the yellow coloring phenolic compounds isolated from the spice turmeric. The effect of curcumins on different stages of development of cancer was studied. Cur I inhibited benzopyrene- (BP) induced forestomach tumors in female Swiss mice, and Cur III inhibited dimethylbenzanthracene- (DMBA) induced skin tumors in Swiss bald mice. Cur I also inhibited DMBA-initiated, tetradeconyl phorbol acetate-promoted skin tumors in female Swiss mice. In vitro 3H-BP-DNA interaction studies, and in vivo carcinogen metabolizing enzyme studies revealed that curcumins exert anticarcinogenic activity by altering the activation and/or detoxification process of carcinogen metabolism. Cur I and Cur III also exhibit in vitro cytotoxicity against human chronic myeloid leukemia, which is dose dependent. This study shows that curcumins inhibit cancer at initiation, promotion and progression stages of development.