Quercetin Potentiates Apoptosis by Inhibiting Nuclear Factor-kappaB Signaling in H460 Lung Cancer Cells

Abstract

The herbal flavonoid quercetin inhibits the growth of various cancer cells, but how it affects human cancer cells, particularly lung cancer cells, is unclear. We investigated the anticancer activity of quercetin and the underlying molecular mechanisms in non-small cell lung cancer (NSCLC) cells. Quercetin strongly inhibited cell proliferation, and increased sub-G1 and apoptotic cell populations regardless of p53 status. Quercetin-induced apoptosis was verified by caspase cleavage, Hoechst staining, trypan blue exclusion, and DNA fragmentation assays. Microarray analysis using H460 cells indicated that quercetin increased the expression of genes associated with death receptor signaling tumor necrosis factor-related apoptosis-inducing ligand receptor (TRAILR), caspase-10, interleukin (IL) 1R DNA fragmentation faotor 45 (DFF45), tumor necrosis factor receptor (TNFR) 1, FAS, inhibitor of kappaBalpha (IκBα)) and cell cycle inhibition growth arrest and DNA-damage inducible 45 (GADD45), p21 Cip1), but decreased the expression of genes involved in nuclear factor (NF)-kappaB activation (NF-κB, IKKα). Further validation assays confirmed that quercetin inhibited growth by suppressing NF-κB and by increasing the expression of death receptors and cell cycle inhibitors. Taken together, these findings suggest that quercetin may be useful in the prevention and therapy of NSCLC.Key words quercetin; lung cancer; apoptosis; death receptor; nuclear factor-kappaB pathway Lung cancer is the leading cause of cancer death in many developed countries because of its poor prognosis. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, of which 70% show advanced-stage disease at the time of diagnosis.1,2) Although various chemical drugs have been developed, 3,4) frequent chemoresistance and side effects in patients with NSCLC require the development of new preventive and therapeutic agents. High intake of flavonoids from fruits and vegetables is associated with a low risk of various cancers, 5-10) including lung cancer. 11,12) Of these polyphenolic flavonoids, quercetin is readily found in fruits, vegetables, green and black tea, and various medical plants such as Euonymus alatus (Thunb.) Sieb. Quercetin can act as either an antioxidant or a prooxidant depending on its concentration (1-40 µm or 40-100 µm, respectively). 13,14) Numerous studies have reported a broad range of pharmacological properties of quercetin, including benefits for inflammation, 15) atherosclerosis, 16) hypertension, 17) and neurodegeneration. 18,19) In addition to these beneficial effects, quercetin plays preventive and therapeutic roles in various types of cancer and cancer cells. [20][21][22][23][24][25] However, the anticancer effect of quercetin in NSCLC cells has been rarely addressed, and the underlying molecular mechanism remains to be determined.Here, we investigated the growth inhibitory role of quercetin in three NSCLC cell lines and found that its effect is p53-independent and triggered by apoptosis. Subsequent microarray analysis usin...

Neuroprotective activities of curcumin and quercetin with potential relevance to mitochondrial dysfunction induced by oxaliplatin

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Protective mechanism of quercetin on acute myocardial infarction in rats

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“…Kuersetin potansiyel bir anti-kanser ajan olarak umut vadetmektedir. Farklı kanser hücre hatlarında apoptozu aktive ettiği, küçük hücreli olmayan akciğer kanserinde hücre proliferasyonunu güçlü bir şekilde inhibe ettiği ve servikal kanserlerde nF-kB ekspresyonunun azaltılmasıyla apoptotik hücre popülasyonunu arttırdığı gösterilmiştir (64,65). Bu hücrelerde pro-apoptotik Bax proteininin ekspresyonu yanında, sitozolik sitokrom c, Apaf-1 (apoptotic peptidase activating factor 1), p53, kaspaz-9 ve kaspaz-3 ile kesilmiş poli (ADP-riboz) polimeraz (PArP) miktarları da artmıştır.…”