Kaempferol induces autophagy through AMPK and AKT signaling molecules and causes G2/M arrest via downregulation of CDK1/cyclin B in SK-HEP-1 human hepatic cancer cells

Huang, Wenwen; Tsai, Shih‐Chang; Peng, Shu‐Fen; Lin, Ming-Tzer; Chiang, Jo‐Hua; Chiu, Yu–Jen; Fushiya, Shinji; Tseng, Michael T.; Yang, Jai Sing

doi:10.3892/ijo.2013.1909

Cited by 116 publications

(96 citation statements)

References 35 publications

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“…We further examined the effect of kaempferol and kaempferide on SOD1 aggregation by using a series of concentrations based on previous studies (Fig. 3C) 21, 22 . As results, kaempferol (from 0.3 µM to 10 µM) and kaempferide (from 5 µM to 50 µM) significantly decreased the aggregates.…”

Section: Resultsmentioning

confidence: 99%

The effects of Brazilian green propolis that contains flavonols against mutant copper-zinc superoxide dismutase-mediated toxicity

Ueda

Inden

Shirai

et al. 2017

Sci Rep

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective and progressive loss of motor neurons. The purpose of this study was to clarify effects of brazilian green propolis and the active ingredient against ALS-associated mutant copper-zinc superoxide dismutase (SOD1)-mediated toxicity. Ethanol extract of brazilian green propolis (EBGP) protected N2a cells against mutant SOD1-induced neurotoxicity and reduced aggregated mutant SOD1 by induction of autophagy. Kaempferide and kaempferol, the active ingredients of EBGP, also inhibited mutant SOD1-induced cell death and reduced the intracellular mutant SOD1 aggregates. Both kaempferide and kaempferol significantly suppressed mutant SOD1-induced superoxide in mitochondria. Western blot analysis showed that kaempferol potentially induced autophagy via the AMP-activated protein kinase (AMPK) - the mammalian target of rapamycin (mTOR) pathway. These results suggest that EBGP containing the active ingredient against mutant SOD1-mediated toxicity is a promising medicine or health food for prevention and treatment of ALS.

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Section: Resultsmentioning

confidence: 99%

The effects of Brazilian green propolis that contains flavonols against mutant copper-zinc superoxide dismutase-mediated toxicity

Ueda

Inden

Shirai

et al. 2017

Sci Rep

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“…Kaempferol is a flavonol present in fruits and vegetables, including onions, kale, broccoli, apples, cherries, berries, tea and red wine (11,12). Kaempferol has many biological properties, including anti-cancer, antioxidant activity, antiinflammatory effects (12,21).…”

Section: Discussionmentioning

confidence: 99%

“…Kaempferol is a dietary flavonoid and is found in fruits and vegetables and in traditional Chinese medicines (11,12).…”

Section: Introductionmentioning

confidence: 99%

Kaempferol induces ATM/p53-mediated death receptor and mitochondrial apoptosis in human umbilical vein endothelial cells

Lee

Yang

Tsai

et al. 2016

International Journal of Oncology

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Abstract. Kaempferol is a member of the flavonoid compounds found in vegetables and fruits. It is shown to exhibit biological impact and anticancer activity, but no report exists on the angiogenic effect of kaempferol and induction of cell apoptosis in vitro. In this study, we investigated the role of kaempferol on anti-angiogenic property and the apoptotic mechanism of human umbilical vein endothelial cells (HUVECs). Our results demonstrated that kaempferol decreased HUVEC viability in a time-and concentration-dependent manner. Kaempferol also induced morphological changes and sub-G1 phase cell population (apoptotic cells). Kaempferol triggered apoptosis of HUVECs as detecting by DNA fragmentation, comet assay and immunofluorescent staining for activated caspase-3. The caspase signals, including caspase-8, -9 and -3, were time-dependently activated in HUVECs after kaempferol exposure. Furthermore, pre-treatment with a specific inhibitor of caspase-8 (Z-IETD-FMK) significantly reduced the activity of caspase-8, -9 and -3, indicating that extrinsic pathway is a major signaling pathway in kaempferoltreated HUVECs. Importantly, kaempferol promoted reactive oxygen species (ROS) evaluated using flow cytometric assay in HUVECs. We further investigated the upstream extrinsic pathway and showed that kaempferol stimulated death receptor signals [Fas/CD95, death receptor 4 (DR4) and DR5] through increasing the levels of phosphorylated p53 and phosphorylated ATM pathways in HUVECs, which can be individually confirmed by N-acetylcysteine (NAC), ATM specific inhibitor (caffeine) and p53 siRNA. Based on these results, kaempferol-induced HUVEC apoptosis was involved in an ROS-mediated p53/ATM/death receptor signaling. Kaempferol might possess therapeutic effects on cancer treatment in anti-vascular targeting.

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“…In HT-29 colon cancer cells, the treatment of kaempferol (0–60 μM) provoked apoptosis by activating the death receptor pathway and mitochondrial pathway [109]. Another study in SK-HEP-1 human liver cancer cells found G 2 /M cell cycle arrest and autophagy following kaempferol treatment, which might be the result of the modulation of CDK1/cyclin B expression and AMPK and AKT signaling pathways [110]. Kaempferol induced apoptosis in MCF-7 breast cancer cells [111].…”

Section: Experimental Studiesmentioning

confidence: 99%

Natural Polyphenols for Prevention and Treatment of Cancer

et al. 2016

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There is much epidemiological evidence that a diet rich in fruits and vegetables could lower the risk of certain cancers. The effect has been attributed, in part, to natural polyphenols. Besides, numerous studies have demonstrated that natural polyphenols could be used for the prevention and treatment of cancer. Potential mechanisms included antioxidant, anti-inflammation as well as the modulation of multiple molecular events involved in carcinogenesis. The current review summarized the anticancer efficacy of major polyphenol classes (flavonoids, phenolic acids, lignans and stilbenes) and discussed the potential mechanisms of action, which were based on epidemiological, in vitro, in vivo and clinical studies within the past five years.

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Kaempferol induces autophagy through AMPK and AKT signaling molecules and causes G2/M arrest via downregulation of CDK1/cyclin B in SK-HEP-1 human hepatic cancer cells

Cited by 116 publications

References 35 publications

The effects of Brazilian green propolis that contains flavonols against mutant copper-zinc superoxide dismutase-mediated toxicity

The effects of Brazilian green propolis that contains flavonols against mutant copper-zinc superoxide dismutase-mediated toxicity

Kaempferol induces ATM/p53-mediated death receptor and mitochondrial apoptosis in human umbilical vein endothelial cells

Natural Polyphenols for Prevention and Treatment of Cancer

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