Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Oct 10;23(10):2592.
doi: 10.3390/molecules23102592.

Kaempferol Attenuates ROS-Induced Hemolysis and the Molecular Mechanism of Its Induction of Apoptosis on Bladder Cancer

Ping Wu  1   2 , Xiaofeng Meng  3   4 , Huade Zheng  5 , Qin Zeng  6 , Tianfeng Chen  7 , Wen Wang  8   9 , Xia Zhang  10 , Jianyu Su  11   12   13
Affiliations

Kaempferol Attenuates ROS-Induced Hemolysis and the Molecular Mechanism of Its Induction of Apoptosis on Bladder Cancer

Ping Wu et al. Molecules. .

Abstract

Bladder cancer has become the most common malignant urinary carcinoma. Studies have shown that significant antioxidant and bladder cancer-fighting properties of several plant-based diets like Psidium guajava, ginger and amomum, are associated with their high kaempferol content. In this paper, we evaluated the antioxidant and anticancer activities of kaempferol and its mechanism of induction to apoptosis on bladder cancer cells. Our findings demonstrated that kaempferol showed an obvious radical scavenging activity in erythrocytes damaged by oxygen. Kaempferol promoted antioxidant enzymes, inhibited ROS generation and lipid peroxidation and finally prevented the occurrence of hemolysis. Additionally, kaempferol exhibited a strong inhibitory effect on bladder cancer cells and high safety on normal bladder cells. At the molecular level, kaempferol suppressed EJ bladder cancer cell proliferation by inhibiting the function of phosphorylated AKT (p-AKT), CyclinD1, CDK4, Bid, Mcl-1 and Bcl-xL, and promoting p-BRCA1, p-ATM, p53, p21, p38, Bax and Bid expression, and finally triggering apoptosis and S phase arrest. We found that Kaempferol exhibited strong anti-oxidant activity on erythrocyte and inhibitory effects on the growth of cancerous bladder cells through inducing apoptosis and S phase arrest. These findings suggested that kaempferol might be regarded as a bioactive food ingredient to prevent oxidative damage and treat bladder cancer.

Keywords: anti-bladder cancer cell activity; antioxidant activity; apoptosis; kaempferol; p53 pathway.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structure of kaempferol.
Figure 2
Figure 2
Protection of kaempferol against AAPH-induced oxidative damage. (A) Kaempferol inhibited AAPH-induced ROS generation in erythrocytes. (B) Kaempferol attenuated AAPH-induced MDA generation in erythrocytes. (C) Kaempferol enhanced AAPH-induced SOD activity in erythrocytes. (D) Kaempferol enhanced AAPH-induced GPx activity in erythrocytes. All data are expressed as means ± SD of triplicates. Means with different letters (a, b, c) are statistically different at p < 0.05 level.
Figure 3
Figure 3
Protective effects of kaempferol on the images of human erythrocytes by scanning electron microscopy. (A) Normal human erythrocytes. (B) Damaged erythrocytes by 100 mM AAPH alone for 2 h. (C) Pretreated erythrocytes with 80 μM kaempferol before erythrocytes were cultured with 100 mM AAPH for 2 h.
Figure 4
Figure 4
Protective effects of kaempferol on bladder cancer EJ cells. (A) The effects of kaempferol on the cell viability of an EJ cell and a normal bladder cell SV-HUC-1. (B) Morphological changes of EJ cells as examined by phase-contrast microscopy (magnification, 200×). (C) Kaempferol-induced S cell cycle arrest in EJ cells. Cell cycle distribution of EJ cells treated with kaempferol was analyzed by flow cytometric analysis. ∗ p < 0.05 versus the control.
Figure 5
Figure 5
The expression levels of signal protein in EJ cells treated with kaempferol by western blotting. (A) p-BRCA1, p-ATM, p-p53, and T-p53. (B) Bax, Bad, Bid, Mcl-1, and Bcl-xL. (C) Cyclin D1, CDK6, p27, p21, and p38. (D) Phosphorylated AKT (p-AKT) and total AKT (t-AKT). β-actin was used as the loading control. The protein expression levels are percentages of the control. Relative intensity was shown above each immunoblotted protein and condition. Representative images of three independent experiments are presented.
Figure 6
Figure 6
Proposed signaling pathway triggered by kaempferol in EJ cells.
See this image and copyright information in PMC

References

    1. Garg M. Urothelial cancer stem cells and epithelial plasticity: Current concepts and therapeutic implications in bladder cancer. Cancer Metastasis Rev. 2015;34:691–701. doi: 10.1007/s10555-015-9589-6. - DOI - PubMed
    1. Kasala E.R., Bodduluru L.N., Madana R.M., Athira K.V., Gogoi R., Barua C.C. Chemopreventive and therapeutic potential of chrysin in cancer: Mechanistic perspectives. Toxicol. Lett. 2015;233:214–225. doi: 10.1016/j.toxlet.2015.01.008. - DOI - PubMed
    1. Chen A.Y., Chen Y.C. A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention. Food Chem. 2013;138:2099–2107. doi: 10.1016/j.foodchem.2012.11.139. - DOI - PMC - PubMed
    1. Wang Y., Zhang G., Pan J., Gong D. Novel insights into the inhibitory mechanism of kaempferol on xanthine oxidase. J. Agric. Food Chem. 2015;63:526–534. doi: 10.1021/jf505584m. - DOI - PubMed
    1. Yao S., Wang X., Li C., Zhao T., Hai J., Fang W. Kaempferol inhibits cell proliferation and glycolysis in esophagus squamous cell carcinoma via targeting EGFR signaling pathway. Tumour Biol. 2016;37:10247–10256. doi: 10.1007/s13277-016-4912-6. - DOI - PubMed

MeSH terms