ReviewA review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention
Highlights
► Kaempferol reduces the risk of chronic diseases, especially cancer. ► Kaempferol augments human body’s antioxidant defence against free radicals. ► Kaempferol modulates apoptosis, angiogenesis, inflammation, and metastasis. ► Nanotechnology can improve the bioavailability of kaempferol.
Introduction
Cancer manifests itself in a number of forms, all marked by the same unrestrained proliferation of cells. There currently exist many techniques to manage this leading cause of mortality. Surgery, radiation treatments, and chemotherapy have shown remarkable efficacy in cancer treatments, but they are not without serious shortcomings. None of these is a panacea for such a resilient disease. Cancer cells adapt to treatment; they have a stubborn inclination to mutate or metastasize. Once a tumor is eliminated, its remnants tend to linger. Chemotherapy is also notorious for inducing a plethora of adverse effects in patients. From vomiting to hair loss, quality of life can be severely compromised during rounds of chemotherapy.
Flavonoids are polyphenolic compounds commonly found in plants and constitute a significant part of the human diet (Wojdylo, Oszmianski, & Czemerys, 2007). The antioxidant and anti-inflammatory capacities of these compounds are well documented (Seifried, Anderson, Fisher, & Milner, 2007), and many display cancer fighting potential. Flavonoids were reported to inhibit VEGF expression, cancer cell proliferation and angiogenesis (Luo, Jiang, King, & Chen, 2008). Of particular interest is the flavonoid kaempferol (Fig. 1). A member of the flavonols, kaempferol is abundantly found in tea, broccoli, apples, strawberries, and beans (Somerset & Johannot, 2008). It has been demonstrated to invoke several different mechanisms in the regulation of cancer cells. Not only is kaempferol a potent promoter of apoptosis (Ramos, 2007), but it also modifies a host of cellular signaling pathways. In addition, kaempferol is much less toxic to normal cells in comparison to standard chemotherapy drugs (Zhang, Chen, Li, Chen, & Yao, 2008). This review aims to catalogue the numerous anticancer properties of kaempferol and the cellular processes affected. An investigation into the bioavailability of kaempferol is also conducted.
Section snippets
Extraction
An economic and low cost method for kaempferol preparation was proposed by enzymatic hydrolysis using two kaempferol glycosides in tea seed (Park, Rho, Kim, & Chang, 2006). The conventional organic solvent extraction method has been used to extract the two kaempferol glycosides (Park et al., 2006, Sekine et al., 1991, Sekine et al., 1993). However, this procedure is time-consuming and labour-intensive. Handling of large volumes of hazardous solvents and extended concentration steps can result
Signal transduction
In the context of a multicellular organism, individual cells can only work in cohort when the proper channels of communication are open. Cells must be able to respond appropriately to a wide variety of external stimuli. There exist many pathways for translating chemical messages into physical changes in gene expression, one of which is the MAPK/ERK pathway. This signal route begins with the binding of an extracellular messenger to a specific membrane protein. The membrane protein can then
Effect on angiogenesis
Like every other part of the body, cancer cells require a supply of oxygen and nutrients, furnished by a network of circulating blood vessels. The formation of new blood vessels designed to meet the growing needs of the tumor is termed angiogenesis, of which vascular endothelial growth factor (VEGF) is the primary mediator (Ferrara, 2004). Recent research efforts have shown the efficacy of kaempferol in impairing cancer angiogenesis both in vitro and in vivo through inhibiting VEGF secretion in
Effect on metastasis
One of the most lethal aspects of cancer is its ability to disseminate to other parts of the body. As opposed to localised tumors, metastasized cancer presents a far more difficult problem to treat. Surgery can remove a primary tumor, but these secondary growths are prone to resurface once eliminated. In order to spread, malignant cells must first degrade their surrounding extracellular matrix (ECM), making their way through to the body’s vascular system for a free ride. To break down the
Effect on inflammation
The inflammatory response is a commonplace bodily process meant to help facilitate healing. The signs of inflammation are evoked by vasodilation and increased blood vessel permeability, which manifest as redness and swelling. The heightened blood flow allows extra blood cells to reach the site of injury to begin eliminating intruders, while simultaneously regenerating the original tissue. Inflammation is a highly regulated process built on the secretion of a plethora of chemical messengers.
Bioavailability and epidemiology of anticarcinogenic effects
Up to this point, an incredible amount of research has been conducted detailing the in vitro effects of dietary flavonoids including kaempferol. The question still remains, though, as to whether kaempferol is effective in helping real patients suffering from cancer. Low intake of vegetables has been consistently associated with an increased risk of cancer (Banks, 2000). Encouragingly, a large number of population studies have confirmed that a diet high in flavonoids, namely kaempferol, reduces
Nanotechnology
Perhaps the most promising and innovative technique to improving bioavailability, though, is through nanotechnology. The coating of certain chemicals with a layer of nanoparticles increases the permeability and amount of that substance to reach systemic circulation. The capsule of nanoparticles can help shield kaempferol from efflux transporters and coax cells to transport the nanoparticle complex inwards, in addition to preserving its structural integrity. Research done on EGCG, another
Conclusions
Upon examination of its remarkable catalogue of cancer fighting properties, it is plain to see that kaempferol is brimming with potential. In the in vitro setting, this flavonoid boasts a wide spectrum of cancer targeting effects in apoptosis, angiogenesis, metastasis, and inflammation. Most significantly, kaempferol is not a compound which concentrates its efforts in one area. If cancerous cells adapt to VEGF inhibition, they remain vulnerable to the other destructive effects of kaempferol.
Acknowledgments
This research was supported by a West Virginia Experimental Program to Stimulate Competitive Research grant and an NIH grant (5P20RR016477 and 8P20GM104434) from the National Center for Research Resources awarded to the West Virginia IDeA Network of Biomedical Research Excellence.
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