Quercetin Induces Necrosis and Apoptosis in SCC-9 Oral Cancer Cells

Haghiac, Maricela; Walle, Thomas

doi:10.1207/s15327914nc5302_11

Cited by 94 publications

(56 citation statements)

References 47 publications

(52 reference statements)

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“…Asynchronized cells were plated in 60 mm 2 plates at 0.1×10 6 cells/ml, grown until 75-80% confluency then treated with 0, 5, 10, 25 and 50 μM flavonoid for 24, 48 and 72 h [4]. The cells were collected by trypsinization, washed twice with cold phosphate-buffered saline (PBS), and centrifuged.…”

Section: Cell Cycle Analysismentioning

confidence: 99%

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Cancer chemopreventive properties of orally bioavailable flavonoids—Methylated versus unmethylated flavones

Walle

Kawamori

et al. 2007

Biochemical Pharmacology

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197

175

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Poor oral bioavailability has been a major limitation for the successful use of dietary flavonoids as cancer chemopreventive agents. In this study, we examined fully methylated flavones as promising improved agents. In the humanoral SCC-9 cancer cells, 5,7-dimethoxyflavone and 5,7,4'-trimethoxyflavone were both ten times more potent inhibitors of cell proliferation (IC 50 values 5-8 μM) than the corresponding unmethylated analogs chrysin and apigenin. Flow cytometry indicated that both methylated flavones arrested the SCC-9 cells in the G1 phase with a concomitant decrease in the S phase, dramatically different from the unmethylated analogs, which promoted G2/M phase arrest. Both methylated compounds inhibited the proliferation of two other cancer cell lines with very little effect on two immortalized normal cell lines. Examination of additional flavone structures indicated that methylated flavones in general have antiproliferative properties. Finally, we demonstrated that 5,7-dimethoxyflavone, in contrast to its unmethylated analog chrysin, was well absorbed and had high oral bioavailability as well as tissue accumulation in vivo in the rat. Thus, fully methylated flavones appear to have great potential as cancer chemopreventive/ chemotherapeutic agents, in particular in oral cancer.

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Section: Cell Cycle Analysismentioning

confidence: 99%

“…Novel biochemical mechanisms are still being revealed at an accelerating rate in cell culture experiments [4][5][6][7]. However, extending such studies to the in vivo situation in animals or even more so in humans, using modest clinically tolerable doses, in most cases have been unsuccessful.…”

Section: Introductionmentioning

confidence: 99%

Cancer chemopreventive properties of orally bioavailable flavonoids—Methylated versus unmethylated flavones

Walle

Kawamori

et al. 2007

Biochemical Pharmacology

Self Cite

197

175

View full text Add to dashboard Cite

show abstract

“…This most recently includes effects on VEGF and HIF-1 expression via PI3K/AKT pathways [7] or via ARNT [8], inactivation of EGFR [9] and inhibition of thioredoxin reductase [10], thymidylate synthase [11] and the MDM2 oncogene [12] as well as effects on cancer cell resistance by targeting the molecular chaperone glucose-regulated protein 78 [13].…”

Section: Introductionmentioning

confidence: 99%

Methoxylated flavones, a superior cancer chemopreventive flavonoid subclass?

Walle

2007

Seminars in Cancer Biology

263

181

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Dietary flavonoids and other polyphenols show great potential as cancer chemopreventive agents in cell culture studies. This does not translate well into in vivo activity, because of extensive conjugative metabolism of these compounds in the intestine and liver. This paper presents a review of a flavonoid subclass in which all hydroxyl groups are capped by methylation. This results in dramatically increased metabolic stability and membrane transport in the intestine/liver, thus improving oral bioavailability. The methoxyflavones also show increased cancer chemopreventive properties. At the cancer initiation stage, bioactivation of polyaromatic hydrocarbon carcinogens and binding to DNA are markedly diminished through effects on CYP1A1/1B1 transcription but also through direct interactions with the proteins. At the cancer promotion stage, the proliferation of cancer cells, but not normal cells, is inhibited with greater potency than with the unmethylated flavones. Limited mechanistic experiments, such as of effects on cell cycle regulation, indicate that the mechanisms of methoxyflavone activities are unique, including aromatase inhibition. The cancer preventive effects and mechanisms of the polymethoxyflavones, such as tangeretin and nobiletin, are discussed in comparison. It is concluded that the methoxyflavones have properties that may make them particularly useful as cancer chemopreventive agents.

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“…Regardless of recent progress in oral squamous cell carcinoma therapy, the prognosis of these patients has not ameliorated significantly over the past 20 years. Development of resistance and unbearable side effects of current chemotherapy drugs are considerable problems that need to be settled (Haghiac and Walle 2005). In cancer therapy, almost 74 % of anticancer agents are naturally-derived products; therefore, one of the reasonable and effective strategies regarding cancer chemoprevention is the research for new anti-tumour agents from plant sources (Gordaliza 2007).…”

mentioning

confidence: 99%

Cell cycle arrest and mechanism of apoptosis induction in H400 oral cancer cells in response to Damnacanthal and Nordamnacanthal isolated from Morinda citrifolia

et al. 2016

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Oral cancer is the eleventh most prevalent cancer worldwide. The most prevalent oral cancer is oral squamous cell carcinoma (OSCC). Damnacanthal (DAM) and nordamnacanthal (NDAM), the anthraquinone compounds, are isolated from the root of Morinda citrifolia L. (Noni), which has been used for the treatment of several chronic diseases including cancer. The objectives of this study were to evaluate the cytotoxicity, cell death mode, cell cycle, and the molecular mechanism of apoptosis induced by DAM and NDAM on OSCC. The cytotoxic effects of these compounds against OSCC cell lines were determined by MTT assay. The cell death mode was analysed by DNA laddering and FITC-annexin V/PI flow cytometric assays. In addition, the mechanism of apoptosis induced by DAM and NDAM was detected using mitochondrial membrane potential, Cytochrome c, and caspases assays. Finally, the effect of DAM and NDAM on cell cycle phase distribution of OSCC cells was detected by flow cytometry. In the present study, DAM and NDAM showed cytotoxicity towards OSCC cell lines and the maximum growth inhibition for both compounds was observed in H400 cells with IC 50 value of 1.9 and 6.8 lg/ml, respectively, after 72 h treatment. The results also demonstrated the inhibition of H400 OSCC cells proliferation, internucleosomal cleavage of DNA, activation of intrinsic apoptosis pathway, and cell cycle arrest caused by DAM and NDAM. Therefore, these findings suggest that DAM and NDAM can be potentially used as antitumor agents for oral cancer therapy.

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Quercetin Induces Necrosis and Apoptosis in SCC-9 Oral Cancer Cells

Cited by 94 publications

References 47 publications

Cancer chemopreventive properties of orally bioavailable flavonoids—Methylated versus unmethylated flavones

Cancer chemopreventive properties of orally bioavailable flavonoids—Methylated versus unmethylated flavones

Methoxylated flavones, a superior cancer chemopreventive flavonoid subclass?

Cell cycle arrest and mechanism of apoptosis induction in H400 oral cancer cells in response to Damnacanthal and Nordamnacanthal isolated from Morinda citrifolia

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