Turmeric, derived from the plant Curcuma longa, is a gold-colored spice commonly used in the Indian subcontinent, not only for health care but also for the preservation of food and as a yellow dye for textiles. Curcumin, which gives the yellow color to turmeric, was first isolated almost two centuries ago, and its structure as diferuloylmethane was determined in 1910. Since the time of Ayurveda (1900 Bc) numerous therapeutic activities have been assigned to turmeric for a wide variety of diseases and conditions, including those of the skin, pulmonary, and gastrointestinal systems, aches, pains, wounds, sprains, and liver disorders. Extensive research within the last half century has proven that most of these activities, once associated with turmeric, are due to curcumin. Curcumin has been shown to exhibit antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, and anticancer activities and thus has a potential against various malignant diseases, diabetes, allergies, arthritis, Alzheimer's disease, and other chronic illnesses. These effects are mediated through the regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other enzymes. Curcumin exhibits activities similar to recently discovered tumor necrosis factor blockers (e.g., HUMIRA, REMICADE, and ENBREL), a vascular endothelial cell growth factor blocker (e.g., AVASTIN), human epidermal growth factor receptor blockers (e.g., ERBITUX, ERLOTINIB, and GEFTINIB), and a HER2 blocker (e.g., HERCEPTIN). Considering the recent scientific bandwagon that multitargeted therapy is better than monotargeted therapy for most diseases, curcumin can be considered an ideal "Spice for Life".

Curcumin: The Indian solid gold

Curcumin and cancer: An “old-age” disease with an “age-old” solution

Curcumin is a natural polyphenol used in ancient Asian medicine. Since the first article referring to the use of curcumin to treat human disease was published in The Lancet in 1937, >2,600 research studies using curcumin or turmeric have been published in English language journals. The mechanisms implicated in the inhibition of tumorigenesis by curcumin are diverse and appear to involve a combination of antiinflammatory, antioxidant, immunomodulatory, proapoptotic, and antiangiogenic properties via pleiotropic effects on genes and cell-signaling pathways at multiple levels. The potentially adverse sequelae of curcumin's effects on proapoptotic genes, particularly p53, represent a cause for current debate. When curcumin is combined with some cytotoxic drugs or certain other diet-derived polyphenols, synergistic effects have been demonstrated. Although curcumin's low systemic bioavailability after oral dosing may limit access of sufficient concentrations for pharmacologic effects in tissues outside the gastrointestinal tract, chemical analogues and novel delivery methods are in preclinical development to overcome this barrier. This article provides an overview of the extensive published literature on the use of curcumin as a therapy for malignant and inflammatory diseases and its potential use in the treatment of degenerative neurologic diseases, cystic fibrosis, and cardiovascular diseases. Despite the breadth of the coverage, particular emphasis is placed on the prevention and treatment of human cancers.

Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials.

Curcumin, commonly called diferuloyl methane, is a hydrophobic polyphenol derived from rhizome (turmeric) of the herb Curcuma longa. Extensive research over the last half century has revealed important functions of curcumin. In vitro and in vivo research has shown various activities, such as anti-inflammatory, cytokines release, antioxidant, immunomodulatory, enhancing of the apoptotic process, and anti-angiogenic properties. Curcumin has also been shown to be a mediator of chemo-resistance and radio-resistance. The anti-cancer effect has been seen in a few clinical trials, mainly as a native chemoprevention agent in colon and pancreatic cancer, cervical neoplasia and Barrets metaplasia. Some clinical studies with healthy volunteers revealed a low bioavailability of curcumin, casting doubt on the use of curcumin only as food additive. Our clinical experience with curcumin, along with the anti-metabolite gemcitabine in the treatment of patients with advanced pancreatic carcinoma, produced an objective response in less than 10% of patients, with a minor effect on survival. However, the safety of this combination was proved. Curcumin's potent anti-proliferative activity interacting with several intracellular signal transduction pathways may potentiate the anti-tumor effect of gemcitabine. The preclinical data lead to various, but still scarce, clinical studies (some on-going) that demonstrated the possible efficacy of this treatment as a chemopreventive or chemotherapeutic agent. This review will focus on the clinical evidence, including our experience with curcumin as a chemopreventive and therapeutic agent and the in vitro background results.

Curcumin as an Anti-Cancer Agent: Review of the Gap Between Basic and Clinical Applications

Purpose: Curcumin, a component of turmeric, has been shown to suppress inflammation and angiogenesis largely by inhibiting the transcription factor nuclear factor-κB (NF-κB). This study evaluates the effects of curcumin on ovarian cancer growth using an orthotopic murine model of ovarian cancer. Experimental Design: In vitro and in vivo experiments of curcumin with and without docetaxel were done using human ovarian cancer cell lines SKOV3ip1, HeyA8, and HeyA8-MDR in athymic mice. NF-κB modulation was ascertained using electrophoretic mobility shift assay. Evaluation of angiogenic cytokines, cellular proliferation (proliferating cell nuclear antigen), angiogenesis (CD31), and apoptosis (terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling) was done using immunohistochemical analyses. Results: Curcumin inhibited inducible NF-κB activation and suppressed proliferation in vitro. In vivo dose-finding experiments revealed that 500 mg/kg orally was the optimal dose needed to suppress NF-κB and signal transducers and activators of transcription 3 activation and decrease angiogenic cytokine expression. In the SKOV3ip1 and HeyA8 in vivo models, curcumin alone resulted in 49% ( P = 0.08) and 55% ( P = 0.01) reductions in mean tumor growth compared with controls, whereas when combined with docetaxel elicited 96% ( P P = 0.05). In SKOV3ip1 and HeyA8 tumors, curcumin alone and with docetaxel decreased both proliferation ( P P P Conclusions: Based on significant efficacy in preclinical models, curcumin-based therapies may be attractive in patients with ovarian carcinoma.

https://clincancerres.aacrjournals.org/content/clincanres/13/11/3423.full.pdf

Qiufeng Cai

Papers

Antiproliferation and apoptosis induced by curcumin in human ovarian cancer cells.

Hydrogen peroxide-induced apoptosis in human gastric carcinoma MGC803 cells