Kaempferol and quercetin stimulate granulocyte-macrophage colony-stimulating factor secretion in human prostate cancer cells.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) holds immunotherapeutic promise in prostate cancer as it activates the host immune system. Increased production of GM-CSF by cancer cells may facilitate host immunosurveillence by the dendritic cells (DC). Here, we studied the effects of kaempferol (K) and quercetin (Q) on the production of GM-CSF in PC-3 cells. Human cytokine antibody array revealed that treatment with K or Q increased GM-CSF release by PC-3 cells. We further observed by ELISA that K and Q in a concentration-dependent manner increased GM-CSF production without affecting its mRNA levels. Inhibitors of vesicular traffic through the endoplasmic reticulum and Golgi-blocked GM-CSF secretory stimulation. A microtubule-stabilizing agent stimulated GM-CSF release, whereas tubulin and actin depolymerizers suppressed K- or Q-stimulated secretion of GM-CSF. Depletion of extracellular or intracellular calcium ion inhibited the GM-CSF secretion upregulated by both K and Q. Furthermore, we showed that K- and Q-stimulated GM-CSF production involves PLC, PKC, and MEK1/2 activation. Treating human DC with the conditioned medium of K- or Q-incubated PC-3 cells increased chemotaxis of DC, which was significantly attenuated when the conditioned medium was incubated with the neutralizing antibody against GM-CSF. Taken together, our results demonstrate that K and Q activate an immune response in the prostate cancer cells by stimulating GM-CSF production, which in turn could result in the recruitment of DCs to the tumor site.
Bandyopadhyay
Sanghamitra
S
Developmental Toxicology, Indian Institute of Toxicology Research, Lucknow, India.
Romero
Jose R
JR
Chattopadhyay
Naibedya
N
D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D044949:Kaempferols / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D002614:Chelating Agents; D044949:Kaempferols; D047428:Protein Kinase Inhibitors; C006552:kaempferol; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011794:Quercetin; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D010738:Type C Phospholipases; D002118:Calcium