The Flavonoid Quercetin Modulates the Hallmark Capabilities of Hamster Buccal Pouch Tumors

Abstract

Epidemiological studies have consistently demonstrated the protective effects of dietary phytochemicals against cancer risk. Quercetin, a ubiquitous dietary flavonoid, has attracted considerable attention owing to its potent antioxidant and antiproliferative activities. The present study was designed to investigate the chemopreventive as well as the therapeutic ability of quercetin to modulate the key hallmark capabilities of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinomas. We analyzed the expression of markers associated with cell proliferation and survival (PCNA, p21, p53, cyclin D1, GST-P), apoptosis (Fas, Fas-L, Bcl-2 family proteins, cytochrome-C, Apaf-1, caspases, PARP, survivin, cFLIP, API1), invasion (MMPs, TIMP-2, RECK), angiogenesis (PlGF, VEGF, VEGF receptors, HIF-1α), as well as the epigenetic markers (HDAC-1, DNMT1) by immunohistochemical, Western blot, and RT-PCR analyses. Simultaneous administration of quercetin to DMBA-painted hamsters reduced tumor incidence and tumor burden, while posttreatment of quercetin resulted in a significant tumor growth delay. In addition, quercetin administration induced cell cycle arrest and apoptosis and blocked invasion and angiogenesis. We found a positive correlation between the inhibition of HDAC-1 and DNMT1 by quercetin and its anticancer properties. A dietary phytochemical such as quercetin that modulates a plethora of molecules offers promise as an ideal candidate for multitargeted cancer prevention and therapy.

Plant Phytochemicals as Epigenetic Modulators: Role in Cancer Chemoprevention

“…Quercetin administration caused cell cycle arrest and apoptosis and blocked invasion and angiogenesis. This study found a positive correlation between the inhibition of HDAC1 and DNMT1 by quercetin and its anticancer properties (99).…”

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

“…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 using H460 cells indicated that quercetin enhances the expression of genes associated with death receptor signaling and cell cycle inhibition, but decreases the expression of genes involved in nuclear factor (NF)-κB activation.…”

“…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.…”

Efficacy of quercetin against chemically induced murine oral squamous cell carcinoma

“…There are a number of promising studies regarding the anticancer effect of quercetin in oral carcinoma cell lines (29) and animal models (16,30,31). However, studies of in vivo models of different types of OSCCs are controversial (15).…”