Elsevier

Food Chemistry

Volume 138, Issue 4, 15 June 2013, Pages 2099-2107
Food Chemistry

Review
A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention

https://doi.org/10.1016/j.foodchem.2012.11.139Get rights and content

Abstract

Kaempferol is a polyphenol antioxidant found in fruits and vegetables. Many studies have described the beneficial effects of dietary kaempferol in reducing the risk of chronic diseases, especially cancer. Epidemiological studies have shown an inverse relationship between kaempferol intake and cancer. Kaempferol may help by augmenting the body’s antioxidant defence against free radicals, which promote the development of cancer. At the molecular level, kaempferol has been reported to modulate a number of key elements in cellular signal transduction pathways linked to apoptosis, angiogenesis, inflammation, and metastasis. Significantly, kaempferol inhibits cancer cell growth and angiogenesis and induces cancer cell apoptosis, but on the other hand, kaempferol appears to preserve normal cell viability, in some cases exerting a protective effect. The aim of this review is to synthesize information concerning the extraction of kaempferol, as well as to provide insights into the molecular basis of its potential chemo-preventative activities, with an emphasis on its ability to control intracellular signaling cascades that regulate the aforementioned processes. Chemoprevention using nanotechnology to improve the bioavailability of kaempferol is also discussed.

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.

References (83)

  • K.M. Lee et al.

    Kaempferol inhibits UVB-induced COX-2 expression by suppressing Src kinase activity

    Biochemical Pharmacology

    (2010)
  • Y.H. Lee et al.

    Extraction of nobiletin and tangeretin from Citrus depressa Hayata by supercritical carbon dioxide with ethanol as modifier

    Industrial Crops and Products

    (2010)
  • B. Li et al.

    Response surface optimization of supercritical fluid extraction of kaempferol glycosides from tea seed cake

    Industrial Crops and Products

    (2010)
  • B. Li et al.

    Theaflavins inhibit the ATP synthase and the respiratory chain without increasing superoxide production

    Journal of Nutritional Biochemistry

    (2012)
  • Y. Li et al.

    Functional and molecular interactions between the HGF/c-Met pathway and c-Myc in large-cell medulloblastoma

    Laboratory Investigation

    (2008)
  • W. Liu et al.

    Supercritical carbon dioxide extraction of seed oil from Opuntia dillenii Haw. and its antioxidant activity

    Food Chemistry

    (2009)
  • S. Liu et al.

    Optimization of process parameters for supercritical carbon dioxide extraction of Passiflora seed oil by response surface methodology

    Journal of Supercritical Fluids

    (2009)
  • H. Luo et al.

    Kaempferol induces apoptosis in ovarian cancer cells through activating p53 in the intrinsic pathway

    Food Chemistry

    (2011)
  • H. Luo et al.

    Kaempferol inhibits VEGF expression and in vitro angiogenesis through a novel ERK-NFκB-cMyc-p21 pathway

    Food Chemistry

    (2012)
  • R. Marr et al.

    Use of supercritical fluids for different processes including new developments—A review

    Chemical Engineering and Processing

    (2000)
  • U. Nöthlings et al.

    A food pattern that is predictive of flavonol intake and risk of pancreatic cancer

    American Journal of Clinical Nutrition

    (2008)
  • S. Ramos

    Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention

    Journal of Nutritional Biochemistry

    (2007)
  • M.A. Rostagno et al.

    Supercritical fluid extraction of isoflavones from soybean flour

    Food Chemistry

    (2002)
  • E. Ruiz et al.

    Kaempferol inhibits apoptosis in vascular smooth muscle induced by a component of oxidized LDL

    European Journal of Pharmacology

    (2006)
  • S. Scalia et al.

    Analytical and preparative supercritical fluid extraction of Chamomile flowers and its comparison with conventional methods

    Journal of Pharmaceutical and Biomedical

    (1999)
  • R. Schindler et al.

    Flavonoids and vitamin E reduce the release of the angiogenic peptide vascular endothelial growth factor from human tumor cells

    Journal of Nutrition

    (2006)
  • A.H. Schinkel et al.

    Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: An overview

    Advanced Drug Delivery Reviews

    (2003)
  • H.E. Seifried et al.

    A review of the interaction among dietary antioxidants and reactive oxygen species

    Journal of Nutritional Biochemistry

    (2007)
  • T. Sekine et al.

    Two flavonol glycosides from seeds of Camellia sinensis

    Phytochemistry

    (1991)
  • L. Wang et al.

    Dietary intake of selected flavonols, flavones, and flavonoid-rich foods and risk of cancer in middle-aged and older women

    American Journal of Clinical Nutrition

    (2009)
  • A. Wojdyło et al.

    Antioxidant activity and phenolic compounds in 32 selected herbs

    Food Chemistry

    (2007)
  • J.J. Wu et al.

    Sites of stromelysin cleavage in collagen types II, IX, X, and XI of cartilage

    Journal of Biological Chemistry

    (1991)
  • Y. Zhang et al.

    Ginkgo biloba extract kaempferol inhibits cell proliferation and induces apoptosis in pancreatic cancer cells

    Journal of Surgical Research

    (2008)
  • M.L. Ackland et al.

    Synergistic antiproliferative action of the flavonols quercetin and kaempferol in cultured human cancer cell lines

    In Vivo

    (2005)
  • E. Banks

    The epidemiology of ovarian cancer

  • A. Barve et al.

    Metabolism, oral bioavailability and pharmacokinetics of chemopreventive kaempferol in rats

    Biopharmaceutics & Drug Disposition

    (2009)
  • G. Bobe et al.

    Interleukin-6 as a potential indicator for prevention of high risk adenoma recurrence by dietary flavonols in the polyp prevention trial

    Cancer Prevention Research (Phila)

    (2010)
  • G. Bobe et al.

    Flavonoid intake and risk of pancreatic cancer in male smokers (Finland)

    Cancer Epidemiology, Biomarkers & Prevention

    (2008)
  • A. Bonni et al.

    Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms

    Science

    (1999)
  • L.W. Chen et al.

    The two faces of IKK and NF-kappaB inhibition: Prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion

    Nature Medicine

    (2003)
  • Y.Y. Cho et al.

    A regulatory mechanism for RSK2 NH2-terminal kinase activity

    Cancer Research

    (2009)
  • Cited by (0)

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