More than 230,000 diagnosed cases of invasive breast cancer in women was estimated in 2014 and an expected 40,000 deaths attributed to the aggressive carcinoma. An effective approach to diminish the morbidity and mortality of breast cancer is the development of chemopreventive and chemotherapeutic agents. Nutraceuticals have demonstrated their ability to proficiently halt carcinogenesis. The administration of natural compounds able to effectively serve as chemoprevention and chemotherapeutics without causing harm or adverse effects is imperative. Curcumin derived from the rhizome of Curcuma longa L., is a common spice of India, used for centuries because of its medicinal properties. The main component of curcumin possesses a wide range of biological activities; anti-proliferative, anti-inflammatory, and apoptotic characteristics modulated through the inactivation of pathways such as EGK and Akt/mTOR. In addition, curcumin alters the expression of cytokines, transcription factors, and enzymes involved in cell vitality. The in vivo application of curcumin in breast cancer is hindered by its limited bioavailabiity. The synthesis of curcumin analogues and delivery via nanoparticles has demonstrated enhanced bioavailability of curcumin in the malignancy. This review focuses on recent developments in the use of curcumin, curcumin analogues, and novel delivery systems as a preventive and therapeutic method for breast cancer.
Primary prostate cancer, also known as prostate adenocarcinoma (PCa), is a devastating cancer in men worldwide. Europe and developing countries of Asia have fewer reported cases of prostate cancer compared to increasing cases in the United States with higher incidence in Black men. Risk factors associated with prostate cancer are aging, genetics, lifestyle, high body mass index as well as carcinogenic exposure to carbon-containing fuels, tobacco, and charbroiled meats. Hormone therapy and radical prostatectomy are commonly implemented treatments. The more than 20,000 prostate cancer deaths of 2013 suggest there exists a need for enhanced chemopreventive and therapeutic agents for prostate cancer treatment. Fruits, vegetables, and red wines contain high levels of polyphenolic levels. Consumption of these products may provide chemoprevetion of PCa. Curcumin, the major compound from the turmeric rhizome Curcumin Longa has long been used for medicinal purposes as an antiseptic and wound healing. This review focuses on curcumin's therapeutic effectiveness in vitro and in vivo in prostate cancer models. The review will highlight the mechanisms of actions of curcumin in the signaling pathways of prostate cancer.
Curcumin is a popular, plant-derived compound that has been extensively investigated for diverse range of biological activities. Anticancer activity against various types of cancers and high-safety profile associated with curcumin makes it very attractive. In this study, we report the synthesis and evaluation of pyrazole and click chemistry curcumin analogues for Head and Neck cancer. MTT assay against head and neck cancer cell lines CAL27 and UM-SCC-74A revealed the micromolar potency of the synthesized compounds. To determine the possible molecular mechanisms, effect of these analogues in the expression of pSTAT3, pFAK, pERK1/2 and pAKT was studied. Interestingly, compounds 2 and 5 significantly inhibited the pSTAT3 (Tyr 705) phosphorylation. As far as other compounds, they showed potent cytotoxicity against CAL27; however, these compounds did not show any activity on pSTAT3 phosphorylation at IC 50 concentration level. Molecular docking studies revealed the possible binding mode of pyrazole compound 2 in the SH2 domain of STAT3. K E Y W O R D Sclick chemistry curcumin analogue, curcumin, head and neck squamous cell carcinoma, pyrazole analogue Curcumin, a natural polyphenol which is used as a food colourant, and herbal medicine in Asia. Curcumin has received a lot of attention recently due to its high-safety profile and efficacy in treating various diseases.[1-3] Potential anticancer activities associated with curcumin make it a promising therapeutic agent. Apart from anticancer activity, it has shown antioxidant, anti-inflammatory, chemopreventive, chemotherapeutic, antimicrobial and antifungal activities. Curcumin (Figure 1) is being vigorously studied for its effect against breast cancer, prostate cancer, liver cancer, ovarian cancer and cervical cancer.[4] It demonstrated cytotoxic effects against cancer cell lines and cytoprotective effects on non-cancer cells. One of the important aspects of curcumin is its high-safety profile of up to 12 g per day oral administration.[5]Nevertheless, there are a number of challenges, low aqueous solubility, poor absorption and rapid metabolism that limits its therapeutic efficacy.[6] Curcumin can exist as a tautomeric mixture of keto and enol forms in solutions, and the enol form was found to be responsible for the rapid degradation of the curcumin. Chakraborti et al., [7] found that the stability of curcumin was improved when the central diketone moiety of the curcumin was replaced by isooxazole and pyrazole groups. Structural modifications of curcumin were proven to be a meaningful approach to discover analogues with enhanced properties. [8][9][10][11][12] Conjugates of curcumin with β-and γ-cyclodextrin, liposomal and loaded nanoparticles and nanoemulsion are some of the lipid-based colloidal system that has been employed to enhance water solubility and improving its bioavailability.[13] Recent work supports the
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