Kaempferol‐induced growth inhibition and apoptosis in A549 lung cancer cells is mediated by activation of MEK‐MAPK

Abstract

A vast variety of naturally occurring substances have been shown to protect against experimental carcinogenesis and an increasing amount of evidence suggests that kaempferol may have cancer chemopreventative properties. However, the precise underlying protective mechanisms are poorly understood. To elucidate these mechanisms, we challenged human lung cancer cell line A549 with kaempferol and investigated its effects upon cellular growth and signal transduction pathways. Treatment of A549 cells with kaempferol resulted in a dose- and time-dependent reduction in cell viability and DNA synthesis with the rate of apoptosis equivalent to 0.9+/-0.5, 5.2+/-1.5, 16.8+/-2.0, 25.4+/-2.6, and 37.8+/-4.5% on treatment with 0, 17.5, 35.0, 52.5, and 70.0 microM kaempferol, respectively. Concomitantly, kaempferol treatments led to a 1.2-, 2.7-, 3.3-, and 3.4-fold increase in Bax. Similar elevations were also observed in Bad which increased 1.2-, 3.3-, 3.7-, and 4.7-fold, respectively, as compared to control. Bcl-2 and Bcl-xL expression were inhibited in a dose-dependent fashion. While the Akt-1 and phosphorylated Akt-1 were inhibited, the mitogen-activated protein kinase (MAPK) was activated upon kaempferol treatment. Kaempferol induced apoptosis was associated with the cleavage of caspase-7 and poly ADP-ribose polymerase (PARP). Inhibition of MEK1/2 but not PI-3 kinase blocked kaempferol-induced cleavage of caspase-7, PARP cleavage, and apoptosis. The results suggest that inactivation of Akt-1 and alteration of Bcl-2 family of proteins are not sufficient for kaempferol to induce apoptosis and activation of MEK-MAPK is a requirement for kaempferol-induced cell death machinery in A549 cells.

In Vitro Cytotoxicity Effect of Kaempferol in Breast Cancer Cell Lines MCF-7 and Lung Cancer Cell Lines A459

“…This may be due to the presence of flavonoid compound especially kaempferol which also show high cytotoxicity which isolated from high polar fraction of the methanolic extract, in we study the cytotoxicity of MCF-7,A459 cell lines by isolated compound. Our findings are line line with previous studies (Nguyen et al, 2003). Kaempferol is a polyphenol antioxidant found in fruits and vegetables.…”

Ginkgo biloba Extract Kaempferol Inhibits Cell Proliferation and Induces Apoptosis in Pancreatic Cancer Cells

“…The inhibitory effect of kaempferol on cell proliferation may be attributed by its antioxidation capacity and cytotoxic action. Furthermore, kaempferol inhibits the activity of several enzymes involved in cell growth and signal transduction pathway including cAMP-phosphodiesterase and tyrosine kinase [18], cdc25 phosphatase [17], DNA topoisomerase II, topoisomerase I catalyzed DNA religation [19], proline-directed protein kinase fatty acid in human prostate carcinoma cells, and myosin light chain kinase [20]. Several studies on kaempferol have been reported including the activation of human estrogen receptors and unique signaling pathways.…”

Influence of kaempferol, a flavonoid compound, on membrane-bound ATPases in streptozotocin-induced diabetic rats

“…It can be isolated from tea, broccoli, witch-hazel, propslis, grapefruit, and other plants (Yoshida et al, 2008). The medicinal properties of kaempferol include antioxidant, anti-inflammatory, and anticancer activities (Kampkötter et al, 2007;Kim et al, 2010;Nguyen et al, 2003). Several studies have shown that intake of foods containing kaempferol is associated with reductions in mortality, the incidence of myocardial infarction, and the incidence of cerebrovascular disease, as well as with a slightly reduced risk of coronary heart disease (Geleijnse et al, 2002;Knekt et al, 2002;Lin et al, 2006).…”