Reactive Oxygen Species and p53 Mediated Activation of p38 and Caspases is Critically Involved in Kaempferol Induced Apoptosis in Colorectal Cancer Cells.

Abstract

Here the molecular mechanisms of Kaempferol were examined in colorectal cancers (CRCs). Kaempferol significantly exerted antiproliferative and cytotoxic effect in HCT116, HCT15, and SW480 cells. Also, Kaempferol increased sub G1 population, G2/M arrest, and the numbers of TUNEL cells in HCT116 colorectal cancer cells. Also, Kaempferol increased the PARP cleavages and activation of caspase-8, -9, and -3, phospho-p38 MAPK, p53, and p21 in HCT116 and HCT15 cells. Of note, Kaempferol generated reactive oxygen species (ROS) (43.7 ± 0.56 vs 25.8 ± 0.43, P < 0.01) in HCT116 cells and reversely ROS inhibitor NAC obstructed the effects of Kaempferol to cleave PARP and caspase-3 and activate phosphorylation of p38 MAPK in HCT116 colorectal cancer cells. Likewise, pancaspase inhibitor z-vad-fmk, p38 MAPK inhibitor SB203580, and p53 depletion blocked PARP and caspase-3 in Kaempferol treated HCT116 colorectal cancer cells. Therefore, these findings provide novel insight that ROS and p53 signalings mediate p38 phosphorylation and caspase activation in Kaempferol stimulated apoptosis in CRCs.

• Authors: Jhin-Baek Choi, Ju-Ha Kim, Hyemin Lee, Ji-Na Pak, Bum Sang Shim, Sung-Hoon Kim
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 66 Issue 38 Pg. 9960-9967 (Sep 26 2018) ISSN: 1520-5118 [Electronic] United States
• PMID: 30211553 (Publication Type: Journal Article)

Chemical References

• Kaempferols
• Reactive Oxygen Species
• Tumor Suppressor Protein p53
• kaempferol
• p38 Mitogen-Activated Protein Kinases
• Caspases

Topics

• Apoptosis (drug effects)
• Caspases (genetics, metabolism)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Colorectal Neoplasms (genetics, metabolism, physiopathology)
• Humans
• Kaempferols (pharmacology)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Tumor Suppressor Protein p53 (genetics, metabolism)
• p38 Mitogen-Activated Protein Kinases (genetics, metabolism)