RESUMO
Possible enhancements of DNA damage with light of different wavelengths and ionizing radiation (Rhenium-188-a high energy beta emitter (Re-188)) on plasmid DNA and FaDu cells via psoralen were investigated. The biophysical experimental setup could also be used to investigate additional DNA damage due to photodynamic effects, resulting from Cherenkov light. Conformational changes of plasmid DNA due to DNA damage were detected and quantified by gel electrophoresis and fluorescent staining. The clonogene survival of the FaDu cells was analyzed with colony formation assays. Dimethyl sulfoxide was chosen as a chemical modulator, and Re-188 was used to evaluate the radiotoxicity and light (UVC: λ = 254 nm and UVA: λ = 366 nm) to determine the phototoxicity. Psoralen did not show chemotoxic effects on the plasmid DNA or FaDu cells. After additional treatment with light (only 366 nm-not seen with 254 nm), a concentration-dependent increase in single strand breaks (SSBs) was visible, resulting in a decrease in the survival fraction due to the photochemical activation of psoralen. Whilst UVC light was phototoxic, UVA light did not conclude in DNA strand breaks. Re-188 showed typical radiotoxic effects with SSBs, double strand breaks, and an overall reduced cell survival for both the plasmid DNA and FaDu cells. While psoralen and UVA light showed an increased toxicity on plasmid DNA and human cancer cells, Re-188, in combination with psoralen, did not provoke additional DNA damage via Cherenkov light.
Assuntos
Fotoquimioterapia , Rênio , Humanos , Fármacos Fotossensibilizantes/farmacologia , Ficusina/farmacologia , Radioisótopos , DNA/química , Dano ao DNA , Raios UltravioletaRESUMO
For a number of years, oral cancer has remained in the top ten most common types of cancer, with an incidence rate that is steadily increasing. In total, ~75% oral cancer cases are associated with lifestyle factors, including uncontrolled alcohol consumption, betel and tobacco chewing, and the excessive use of tobacco. Notably, betel chewing is highly associated with oral cancer in Southeast Asia. Arsenic is a key environmental toxicant; however, arsenic trioxide has been used as a medicine for the treatment of acute promyelocytic leukemia, highlighting its anticancer properties. The present study aimed to investigate the role of arsenic compounds in the treatment of cancer, using FaDu oral squamous carcinoma cells treated with sodium arsenite (NaAsO2) and dimethyl arsenic acid (DMA). The results demonstrated that FaDu cells exhibited membrane blebbing phenomena and high levels of apoptosis following treatment with 10 µM NaAsO2 and 1 mM DMA for 24 h. The results of cell viability assay demonstrated that the rate of FaDu cell survival was markedly reduced as the concentration of arsenic compounds increased from 10 to 100 µM NaAsO2, and 1 to 100 mM DMA. Moreover, flow cytometry was carried out to further examine the effects of arsenic compounds on FaDu cell cycle regulation; the results revealed that treatment with NaAsO2 and DMA led to a significant increase in the percentage of FaDu cells in the subG1 and G2/M phases of the cell cycle. An Annexin V/PI double staining assay was subsequently performed to verify the levels of FaDu cell apoptosis following treatment with arsenic compounds. Furthermore, the results of the western blot analyses revealed that the expression levels of caspase8, 9 and 3, and poly ADPribose polymerase, as well the levels of phosphorylated JNK and ERK1/2 were increased following treatment with NaAsO2 and DMA in the FaDu cells. On the whole, the results of the present study revealed that treatment with NaAsO2 and DMA promoted the apoptosis of FaDu oral cancer cells, by activating MAPK pathways, as well as the extrinsic and intrinsic apoptotic pathways.
Assuntos
Apoptose/efeitos dos fármacos , Arsênio/farmacologia , Transdução de Sinais/efeitos dos fármacos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Arsênio/metabolismo , Caspases/metabolismo , Caspases/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Humanos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/fisiopatologiaRESUMO
Oral squamous cellular carcinoma (OSCC) is considered a life-threatening disease with detection in late stages, which forces us to opt for dangerous treatment with a combination of chemotherapy and radiotherapy. Herbal components such as piperine and quercetin are derived from edible sources, proving their anticancer potential against oral cancer cells in vitro. Encapsulation into lipid matrix-mediated nanostructured lipid carriers (NLCs) can make both drugs bio-accessible. NLCs were synthesised using the high shear homogenisation method and characterised for their physicochemical properties, followed by in vitro cellular evaluation in FaDu oral cancer cells. NLCs showed negatively charged particles smaller than 180 nm with a polydispersity index (PDI) of <0.3. Both drugs were found to encapsulate sufficiently, with >85% entrapment efficiency and an improved drug release profile compared to their pristine counterparts. Differential scanning calorimetry (DSC) thermograms showed conversion into an amorphous matrix in lyophilized NLCs, which was supported by X-ray diffraction (XRD) analysis. The cytotoxicity assay showed the IC50 concentration for dual drug-loaded NLCs, which was more effective than the pure drug solution. NLCs were found to be internalised in cells in a short time with an almost 95% co-localization rate. Dual drug-loaded NLCs showed maximum depolarisation of the mitochondrial membrane along with more apoptotic changes. Improved apoptosis was confirmed in NLCs using flow cytometry. The in vivo biodistribution of Coumarin-6 labelled NLCs in rats confirmed their efficient distribution in various parts of the oral cavity through oral administration. Optimised dual drug-loaded NLCs provide a better option for delivering both drugs through a single lipid matrix against oral cancer.
Assuntos
Alcaloides/administração & dosagem , Benzodioxóis/administração & dosagem , Neoplasias Bucais/tratamento farmacológico , Sistemas de Liberação de Fármacos por Nanopartículas/química , Piperidinas/administração & dosagem , Alcamidas Poli-Insaturadas/administração & dosagem , Quercetina/administração & dosagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Alcaloides/farmacocinética , Animais , Apoptose/efeitos dos fármacos , Benzodioxóis/farmacocinética , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Ácidos Graxos/química , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Neoplasias Bucais/patologia , Nanoestruturas/química , Tamanho da Partícula , Piperidinas/farmacocinética , Alcamidas Poli-Insaturadas/farmacocinética , Quercetina/farmacocinética , Ratos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Distribuição TecidualRESUMO
Naturally occurring phytochemicals of different origin and structure, arctigenin, bergenin, usnic acid and xanthohumol, were shown to affect Nrf2 pathway in the context of various diseases, but their effect on this pathway in cancer cells was not extensively investigated. This study aimed to evaluate the effect of these compounds on Nrf2 expression and activation in hypopharyngeal FaDu squamous cell carcinoma cells. FaDu cells were treated with 2 or 10 µM arctigenin, bergenin, (+)-usnic acid or xanthohumol for 24 h. While arctigenin, bergenin, and xanthohumol did not affect either Nrf2 expression or activation, (+)-usnic acid treatment increased its transcript level and increased the nuclear/cytosol Nrf2 protein ratio-the measure of Nrf2 pathway activation. Consequently, (+)-usnic acid enhanced the transcription and translation of Nrf2 target genes: NQO1, SOD, and to a lesser extent, GSTP. The treatment of FaDu cells with (+)-usnic acid decreased both GSK-3ß transcript and protein level, indicating its possible involvement in Nrf2 activation. All the tested compounds decreased Bax mRNA but did not change the level of Bax protein. (+)-Usnic acid tended to increase the percentage of early apoptotic cells and LC3 protein, autophagy marker. Significant induction of p53 also was observed after treatment with (+)-usnic acid. In summary, the results of this study indicate that low concentrations of (+)-usnic acid activate Nrf2 transcription factor, most probably as a result of ROS accumulation, but do not lead to FaDu hypopharyngeal carcinoma cells death.
Assuntos
Elementos de Resposta Antioxidante , Benzofuranos/farmacologia , Neoplasias Hipofaríngeas/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas de Neoplasias/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Neoplasias Hipofaríngeas/tratamento farmacológico , Neoplasias Hipofaríngeas/genética , Neoplasias Hipofaríngeas/patologia , Fator 2 Relacionado a NF-E2/genética , Proteínas de Neoplasias/genética , Transdução de Sinais/genéticaRESUMO
Aim: Photodynamic therapy utilizes a light-sensitive molecule that produces reactive oxygen species following irradiation. Photodynamic activities of free Zn phthalocyanine (ZnPc) and its liposomal formulations on human oral squamous cell carcinoma and pharyngeal carcinoma cells were assessed. Materials & methods: ZnPc was incorporated in extruded and nonextruded liposomes composed of palmitoyloleoylphosphatidylglycerol (POPG):palmitoyloleoylphosphatidylcholine (POPC) or POPG:dioleoylphosphatidylethanolamine liposomes and incubated with CAL 27 or FaDu cells. Cell viability was assessed following illumination and further incubation. Results: ZnPc incorporated in extruded POPG:POPC liposomes caused extensive cytotoxicity, while ZnPc in extruded or nonextruded POPG:dioleoylphosphatidylethanolamine liposomes or in multilamellar POPG:POPC liposomes were not effective. Conclusion: Extruded POPG:POPC liposomes are a useful delivery vehicle for ZnPc in photodynamic therapy of oral and pharyngeal cancers.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Neoplasias Faríngeas , Fotoquimioterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Humanos , Indóis , Isoindóis , Lipossomos , Neoplasias Bucais/tratamento farmacológico , Compostos Organometálicos , Neoplasias Faríngeas/tratamento farmacológico , Fármacos Fotossensibilizantes , Carcinoma de Células Escamosas de Cabeça e Pescoço , Compostos de ZincoRESUMO
Omethoate is a broad category of organophosphorous pesticides (OPs) and has toxic effects on human health under long-term, low-dose exposure. However, the role of omethoate in cancer development remains elusive. The incidence of global head and neck squamous cell carcinomas (HNSCC) has markedly increased in recent years. Thus, we examined whether omethoate induced the proliferation of FaDu cells (a cell line of HNSCC) and if so, what the underlying mechanism was. The study revealed that omethoate induced FaDu cell growth in a dose- and time-dependent manner. Omethoate stimulated FaDu cell proliferation was mainly due to enhancing the G1 to S phase transition by flow cytometry analysis. We also found that omethoate up-regulated cyclin D1, a key gene controlling the G1-S transition. Furthermore, we showed that omethoate was capable of activating the Akt/GSK-3ß signaling pathway. Blockage of Akt by siRNA or small molecule inhibitor significantly suppressed omethoate-induced cyclin D1 expression and cell proliferation. Collectively, these findings demonstrated for the first time that omethoate could induce the pharyngeal cancer cell proliferation by activation of the Akt/GSK-3ß/cyclin D1 signaling pathway.
Assuntos
Ciclina D1/metabolismo , Dimetoato/análogos & derivados , Glicogênio Sintase Quinase 3 beta/metabolismo , Praguicidas/toxicidade , Neoplasias Faríngeas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dimetoato/toxicidade , Humanos , Neoplasias Faríngeas/patologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/genética , RNA Interferente Pequeno/genética , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Cancer cells are dependent on aerobic glycolysis for energy production and increased glutamine consumption. HIF-1α and c-MYC transcription factors regulate the expression of glycolytic and glutaminolytic genes. Their activity may be repressed by SIRT6. Head and neck carcinomas show frequent activation of c-MYC function and SIRT6 down-regulation, which contributes to a strong dependence on glucose and glutamine availability. OBJECTIVES: The aim of this study was to compare the influence of HIF-1α and c-MYC inhibitors (KG-548 and 10058-F4, respectively) and potential SIRT6 inducers - resveratrol and its synthetic derivative DMU-212 with the effect of glycolysis and glutaminolysis inhibitors (2-deoxyglucose and aminooxyacetic acid, respectively) on the metabolism and expression of metabolic enzymes in FaDu hypopharyngeal carcinoma cells. MATERIAL AND METHODS: Cell viability was assessed by means of an MTT assay. Quantitative PCR was performed to evaluate the expression of SIRT6, HIF-1α, c-MYC, GLUT1, SLC1A5, HK2, PFKM, PKM2, LDHA, GLS, and GDH. The release of glycolysis and glutaminolysis end-products into the culture medium - lactate and ammonia, respectively - was assessed using standard colorimetric assays. RESULTS: Lactate production was significantly inhibited by 10058-F4, KG-548, and 2-deoxyglucose. Moreover, 10058-F4 strongly reduced the amount of ammonia release. The effects of 10058-F4 activity can be attributed to a reduction in the expression of PKM2 and LDHA. On the other hand, the induction of SIRT6 expression by resveratrol and DMU-212 was not associated with significant modulation of the expression of metabolic enzymes. CONCLUSIONS: Overall, the results of this study indicate that the inhibition of c-MYC may be considered to be a promising strategy of the modulation of cancer-related metabolic changes in head and neck carcinomas.
Assuntos
Glutamina/metabolismo , Glicólise/fisiologia , Neoplasias Hipofaríngeas/metabolismo , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Humanos , Neoplasias Hipofaríngeas/patologia , Tiazóis/farmacologiaRESUMO
Objective:The aim of this study is to investigate the inhibitory effect and mechanism of tanshinone â ¡A combined with cisplatin on tumor Fadu cells in pharyngeal squamous cell carcinoma. Method:Cytotoxicity was determined by CCK8 assay. Flow cytometry was used to detect apoptosis and cell cycle distribution. Western blotting was used to assess the protein expression of related signaling proteins. Result:Compared with the two single drug groups treated with Tan â ¡A and DDP respectively, the combination group showed significantly higher anti-proliferative rate (P<0.01), arrested cell cycle at S phase, and resulted in observably higher apoptotic cell fractions in human hypopharyngeal squamous cell carcinomas Fadu cells; Western blotting showed that the protein expression of cleaved caspase 3 and cleaved PARP increased ,while survivin significantly decreased in the cells treated with the combination of tanshinone â ¡A and cisplatin. Conclusion:Tanshinone â ¡A potentiates the efficacy of Cisplatin in Fadu cells, which may be attributed to the downregulation of survivin protein expression.
Assuntos
Abietanos/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , Proteínas Inibidoras de Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Humanos , Neoplasias Hipofaríngeas/tratamento farmacológico , Neoplasias Hipofaríngeas/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , SurvivinaRESUMO
Objective To investigate the effect and mechanism of action of metformin on proliferation of a human hypopharyngeal carcinoma cell line (FaDu). Methods FaDu cells were treated with metformin (25-125 mmol/l). Cell proliferation was evaluated via CCK-8 assay. Real-time quantitative reverse transcription-polymerase chain reaction was used to evaluate microRNA (miR)-21-5p and PDCD4 (programmed cell death 4) expression. PDCD4 protein was quantified by Western blot. Results Metformin significantly inhibited FaDu cell proliferation in a dose- (25-100 mmol/l) and time-dependent manner (12 h-36 h), significantly downregulated miR-21-5p, and upregulated PDCD4 mRNA and protein expression. Conclusions Metformin significantly inhibited FaDu cell proliferation , possibly via downregulation of miR-21-5p and upregulation of PDCD4.
Assuntos
Proteínas Reguladoras de Apoptose/biossíntese , Proliferação de Células/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Neoplasias Hipofaríngeas/tratamento farmacológico , Metformina/farmacologia , MicroRNAs/biossíntese , Proteínas de Ligação a RNA/biossíntese , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular Tumoral , Humanos , Hipofaringe/patologia , MicroRNAs/genética , RNA Mensageiro/biossíntese , Proteínas de Ligação a RNA/genéticaRESUMO
BACKGROUND: The present study aims to further explore the role of STK33 in hypopharyngeal squamous cell carcinoma (HSCC), with special attention given to the possible relationship between STK33 alteration and calcium. METHODS: An in vivo experiment and microarray analysis were performed to investigate the impact of STK33 knockdown (STK33-RNAi) on the biological behaviors and the gene profile alterations of a HSCC cell line (Fadu). Cell viability and morphological change of Fadu cells in response to Ionomycin were measured by MTT assay and acridine orange staining. The concentration of intracellular calcium ([Ca(2+)]i) was detected by laser scanning confocal microscope with fluo-3/AM. The mRNA and protein expressions of relevant genes were examined by real-time PCR and Western blot. RESULTS: STK33-RNAi retarded the Fadu cell proliferation and the metastasis in nude mice and led to up- and down-regulation of the expressions of abundance of genes, especially, the downregulation of the CAPN1 gene. Ionomycin increased the [Ca(2+)]i and decreased the survival rates of Fadu cells in a time-dependent manner. Moreover, Ionomycin resulted in the elevation of CAPN1 mRNA expression in normal Fadu cells and, conversely, had almost no effect on CAPN1 expression in STK33-RNAi cells. CONCLUSIONS: Findings from this work further validate that STK33 is a potential oncogene and plays an important role in tumorigenesis of HSCC via regulation of numerous genes. In addition, there exists the reciprocal influence between STK33 and [Ca(2+)]i in Fadu cells.
Assuntos
Cálcio/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias Hipofaríngeas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Técnicas de Silenciamento de Genes , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Xenoenxertos , Humanos , Neoplasias Hipofaríngeas/genética , Neoplasias Hipofaríngeas/patologia , Ionomicina/farmacologia , Masculino , Camundongos , Camundongos Nus , Proteínas Serina-Treonina Quinases/genética , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Distribuição Aleatória , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
In case of the release of lanthanides and actinides into the environment, knowledge about their behavior in biological systems is necessary to assess and prevent adverse health effects for humans. We investigated the interaction of europium with FaDu cells (human squamous cell carcinoma cell line) combining analytical methods, spectroscopy, and thermodynamic modeling with in-vitro cell experiments under defined conditions. Both the cytotoxicity of Eu(III) onto FaDu cells and its cellular uptake are mainly concentration-dependent. Moreover, they are governed by its chemical speciation in the nutrient medium. In complete cell culture medium, i.e., in the presence of fetal bovine serum, Eu(III) is stabilized in solution in a wide concentration range by complexation with serum proteins resulting in low cytotoxicity and cellular Eu(III) uptake. In serum-free medium, Eu(III) precipitates as hardly soluble phosphate species, exhibiting a significantly higher cytotoxicity and slightly higher cellular uptake. The presence of a tenfold excess of citrate in serum-free medium causes the formation of Eu(HCit)2(3-) complexes in addition to the dominating Eu(III) phosphate species, resulting in a decreased Eu(III) cytotoxicity and cellular uptake. The results of this study underline the crucial role of a metal ion's speciation for its toxicity and bioavailability.
Assuntos
Európio/farmacologia , Transporte Biológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ácido Cítrico/química , Meios de Cultura/química , Európio/química , Humanos , SolubilidadeRESUMO
Despite the high efficiency of ionizing radiation (IR) to inactivate malignant tumours in general, an appreciable number of individual patients cannot be cured by standard IR. Head and neck tumours are not likely to be cured even by high-dose radiotherapy or chemotherapy. Accordingly, combined therapy is one of the most applicable strategies. Topoisomerase IIα is a ubiquitous enzyme that removes knots and tangles from the genetic material by generating and subsequently resealing of transient double-strand breaks. Due to its unique mechanism of action, topoisomerase IIα is the target of many chemotherapeutic agents such as etoposide. The aim of the present study is to examine the effect of inhibiting topoisomerase IIα by etoposide on the response of squamous cell carcinoma to IR. Results of the present study demonstrated a radiosensitizing effect for the topoisomerase IIα inhibitor etoposide on exponentially growing squamous cell carcinoma (FaDu) cell line especially at low radiation doses. This effect was found to be due to inhibition, by etoposide, of the repair of radiation-induced DNA damage. Cell cycle studies showed that the concentration of etoposide that sensitized the cells to radiation had no effect on the distribution of cells at different phases of the cell cycle. Synchronization of FaDu cells in different cell cycle phases revealed that proliferating G1 and G2 cells are responsible for sensitization of cells at low doses of ionizing radiation. It might, therefore, be concluded that topoisomerase II enzyme may be involved in the repair of radiation-induced DNA damage and consequently its inhibition constitute a strategy for sensitizing tumour cells to ionizing radiation.
Assuntos
Antígenos de Neoplasias/genética , Carcinoma de Células Escamosas/genética , DNA Topoisomerases Tipo II/genética , Proteínas de Ligação a DNA/genética , Neoplasias Faríngeas/genética , Tolerância a Radiação/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Reparo do DNA/genética , Reparo do DNA/efeitos da radiação , Proteínas de Ligação a DNA/antagonistas & inibidores , Etoposídeo/administração & dosagem , Humanos , Neoplasias Faríngeas/patologia , Neoplasias Faríngeas/radioterapia , Tolerância a Radiação/efeitos dos fármacos , Radiação Ionizante , Inibidores da Topoisomerase II/administração & dosagemRESUMO
We investigated Licochalcone-A (Lico-A)-induced apoptosis and the pathway underlying its activity in a pharyngeal squamous carcinoma FaDu cell line. Lico-A purified from root of Glycyrrhiza inflata had cytotoxic effects, significantly increasing cell death in FaDu cells. Using a cell viability assay, we determined that the IC50 value of Lico-A in FaDu cells was approximately 100 µM. Chromatin condensation was observed in FaDu cells treated with Lico-A for 24 h. Consistent with this finding, the number of apoptotic cells increased in a time-dependent manner when FaDu cells were treated with Lico-A. TRAIL was significantly up-regulated in Lico-A-treated FaDu cells in a dose-dependent manner. Apoptotic factors such as caspases and PARP were subsequently activated in a caspase-dependent manner. In addition, levels of pro-apoptotic factors increased significantly in response to Lico-A treatment, while levels of anti-apoptotic factors decreased. Lico-A-induced TRAIL expression was mediated in part by a MAPK signaling pathway involving ERK1/2 and p38. In xenograft mouse model, Lico-A treatment effectively suppressed the growth of FaDu cell xenografts by activating caspase-3, without affecting the body weight of mice. Taken together, these data suggest that Lico-A has potential chemopreventive effects and should therefore be developed as a chemotherapeutic agent for pharyngeal squamous carcinoma.