| Abstrakt: |
Metastatic prostate cancer is the second most common cancer globally, with high mortality and morbidity rates. This study aimed to elucidate the effects of plant-derived kaempferol on the proliferation and migration of human prostate cancer cells at the molecular level. Spectrophotometric analyses proved that kaempferol was stable up to 48 h. Antioxidant properties were investigated by DPPH, CUPRAC, and ABTS methods, and kaempferol possess 3.6 mg/mL DPPH activity. Cytotoxic properties of kaempferol were investigated on various human cancerous cells, including A549(Lung), PC-3(Prostate), NCI-H295R(Adrenal Gland), HUH-7(Liver), HeLa(Cervix) using the Alamar Blue method. Western Blotting and qRT-PCR was employed to analyze Bax, BcL-2, Caspase-3, Caspase-9, Caspase-12, p53, Nf-κB, Smad-4, Kras, APC, MLH-1 expressions. Kaempferol was found the most potent inhibitor against the proliferation of PC-3 cells with an IC50 value of 16.9 µM. Confocal microscopy studies proved that kaempferol was primarily localized in the cytoplasm. Besides, PC-3 cells' migration and colony formation rates significantly (p<0.0001) inhibited 46% and 68%, respectively. Increased protein expressions of TP53 and Nf-κB due to kaempferol activated the E-cadherin, key protein in the migration process. Kaempferol treatment elevated the early rate of apoptosis by regulating apoptotic and antiapoptotic genes and proteins, including Bax, BcL-2, Caspase-3, Caspase-9, Caspase12. Protein expression of Bax was increased 2.63-fold (p<0.001), while BcL-2 protein expression was decreased 87% (p<0.05). Besides, kaempferol modulated PI3K-Akt, TGFβ, and MAPK signaling pathways. mRNA expressions of Smad-4 and Kras were inhibited while APC and MLH-1 mRNA expressions were increased. The low cost and high efficiency of kaempferol used in treating fatal and increased incidence of prostate cancer can reduce and treat prostate cancer by showing a new direction to traditional treatments. [ABSTRACT FROM AUTHOR] |
