Gamma-glutamyltransferase and the risk of head and neck cancer mortality.

BACKGROUND: The purpose of this study was to determine the association between baseline serum gamma-glutamyltransferase levels and the mortality risk of head and neck cancers. METHODS: A total of 481 414 Korean participants aged 40-79 years at enrollment were examined. The hazard ratios for head and neck cancer mortality were analyzed using Cox proportional hazards models, which were adjusted for potential confounding factors. RESULTS: In the overall study population, high gamma-glutamyltransferase levels were significantly associated with head and neck cancers mortality in a dose-response linear relation (p < 0.001). After excluding participants (n = 125) who died of head and neck cancers within five years of enrollment, the main results remained similar to those of the analysis of all 313 head and neck cancers deaths in the study population. CONCLUSION: These findings indicate that serum gamma-glutamyltransferase activity is positively associated with an increased mortality risk in head and neck cancers in a dose-dependent manner.

TLR2 and the NLRP3 inflammasome mediate IL-1ß production in Prevotella nigrescens-infected dendritic cells.

Prevotella nigrescens is an oral pathogen that is frequently observed in the subgingival plaque of periodontitis patients. Interleukin-1ß (IL-1ß) is known to be involved in the immunopathology of periodontal diseases and has been implicated in the destruction of bone. In this study, we investigated the mechanism of IL-1ß production by P. nigrescens in murine bone marrow-derived dendritic cells (BMDCs). Our results showed that a host receptor, Toll-like receptor 2 (TLR2), but not TLR4 is required for pro-IL-1ß induction and nucleotide-binding oligomerization domain like receptor pyrin domain containing 3 (NLRP3) priming in BMDCs in response to P. nigrescens and activation of the NLRP3 inflammasome is necessary for processing of pro-IL-1ß into mature IL-1ß. In addition, an inhibitor assay revealed that production of reactive oxygen species, P2X7R activity, and release of cathepsin B are involved in IL-1ß production in BMDCs in response to P. nigrescens.

Risk factors of head and neck cancer mortality compared with those of all-cause and all-cancer mortalities.

This study aimed to clarify the risk factors of head and neck cancer (HNC) mortality, relative to those of all-cause and all-cancer mortalities, using the Korean National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) data set. Data from 238 HNC deaths, 14,769 all-cancer deaths, and 38,086 all-cause deaths were extracted during a median follow-up period of 9.5 years. Baseline characteristics were assessed via chi-square tests, t tests, and multivariable logistic regression. HNC mortality was found to be positively associated with male sex, past and current smoking habits, moderate-to-heavy alcohol consumption, and being underweight. In addition, serum gamma-glutamyltransferase level was found to be significantly elevated in cases of HNC mortality. In contrast, obesity, a history of diabetes, and fasting blood glucose levels were found to be inversely associated with overall HNC mortality. Among the HNC subtypes, mortality due to laryngeal cancer was most strongly associated with past and heavy cigarette smoking, and mortality due to oro-/hypopharyngeal cancer was most strongly associated with heavy alcohol consumption. The present study demonstrates that this nationwide, population-based NHIS-HEALS data set can provide useful information for health research and policy development.

Heme Oxygenase-1 is a Key Molecule Underlying Differential Response of TW-37-Induced Apoptosis in Human Mucoepidermoid Carcinoma Cells.

TW-37 is a small-molecule inhibitor of Bcl-2 family proteins, which can induce anti-cancer activities in various types of cancer. In the current study, we investigated the potential molecular mechanism underlying the differential response to TW-37-induced apoptosis in two human mucoepidermoid carcinoma (MEC) cell lines. The differential response and underlying molecular mechanism of human MEC cells to TW-37 was evaluated by trypan blue exclusion assay, western blotting, 4', 6-diamidino-2-phenylindole staining, annexin V/propidium iodide double staining, analysis of the sub-G1 population, human apoptosis array, and measurements of intracellular reactive oxygen species (ROS). TW-37 decreased cell viability and induced apoptosis in YD-15 cells, but not in MC3 cells. Proteome profiling using a human apoptosis array revealed four candidate proteins and of these, heme oxygenase-1 (HO-1) was mainly related to the differential response to TW-37 of YD-15 and MC3 cells. TW-37 also led to a significant increase in intracellular levels of ROS in YD-15 cells, which is associated with apoptosis induction. The ectopic expression of HO-1 recovered YD-15 cells from TW-37-induced apoptosis by reducing intracellular levels of ROS. The expression of HO-1 was reduced through both transcriptional and post-translational modification during TW-37-mediated apoptosis. We conclude that HO-1 is a potential indicator to estimate response to TW37-induced apoptosis in human MEC.

ABT-263 exhibits apoptosis-inducing potential in oral cancer cells by targeting C/EBP-homologous protein.

PURPOSE: ABT-263 is a potent BH3 mimetic that possesses anticancer potential against various types of cancer. In general, this potential is due to its high binding affinity to anti-apoptotic proteins in the Bcl-2 family that disrupt sequestration of pro-apoptotic proteins. In the present study, we sought to identify an alternative regulatory mechanism responsible for ABT-263-mediated anticancer activity in human oral cancer. METHODS: We investigated the in vitro anti-cancer effects of ABT-263 using a trypan blue exclusion assay, Western blotting, DAPI staining, immunofluorescence staining, a live/dead assay, microarray-based expression profiling, and quantitative real-time PCR. In vivo anti-tumorigenic effects of ABT-263 were examined using a nude mouse tumor xenograft model, a TUNEL assay, and immunohistochemistry. RESULTS: We found that ABT-263 suppressed viability and induced apoptosis in human oral cancer-derived cell lines HSC-3 and HSC-4. Subsequent microarray-based gene expression profiling revealed 55 differentially expressed genes in the ABT-263-treatead group, including 12 genes associated with "endoplasmic reticulum stress and apoptosis." Consistent with the microarray results, the mRNA expression levels of the top four genes (CHOP, TRB3, ASNS, and STC2) were found to be significantly increased. In addition, we found that ABT-263 considerably enhanced the expression levels of the C/EBP-homologous protein (CHOP) and its mRNA, resulting in apoptosis induction in four other human oral cancer-derived cell lines (MC-3, YD-15, HN22, and Ca9.22). Extending our in vitro findings, we found that ABT-263 reduced the growth of HSC-4 cells in vivo at a dosage of 100 mg/kg/day without any change in body weight. TUNEL-positive cells were also found to be increased in tumors of ABT-263-treated mice without any apparent histopathological changes in liver or kidney tissues. CONCLUSIONS: These results provide evidence that ABT-263 may serve as an effective therapeutic agent for the treatment of human oral cancer.

Down-regulation and nuclear localization of survivin by sodium butyrate induces caspase-dependent apoptosis in human oral mucoepidermoid carcinoma.

OBJECTIVE: Sodium butyrate (NaBu) is a histone deacetylase inhibitor that possesses an apoptotic ability. However, the molecular mechanism by which NaBu induces apoptosis in human oral mucoepidermoid carcinoma (MEC), a type of salivary gland tumor, remains unclear. MATERIALS AND METHODS: The anticancer effects of NaBu and its related molecular mechanisms were determined by trypan blue exclusion assay, 4'-6-diamidino-2-phenylindole staining, live/dead assay, human apoptosis array, RT-PCR, western blotting, immunocytochemistry, preparation of nuclear fractions, and nude mice tumor xenograft. RESULTS: In this study, we found that NaBu inhibited growth and induced apoptosis in the human oral MEC cell lines MC3 and YD15 with acetylation of histone proteins H2A and H3. NaBu apparently down-regulated survivin protein, as evidenced by the results of the human apoptosis antibody array, and modulated it at the post-translational process. Interestingly, NaBu caused nuclear translocation of survivin protein in both cell lines. NaBu also resulted in decreased expression levels of Bcl-xL mRNA and protein, leading to induction of caspase-dependent apoptosis in human oral MEC cell lines. In addition, NaBu administration inhibited tumor growth in vivo at a dosage of 500 mg/kg/day, but it did not cause any hepatic or renal toxicity. CONCLUSION: This study provides new insights into the molecular mechanism of apoptotic actions by NaBu in human oral MEC and the basis of its clinical application for the treatment of human oral MEC.

Nitidine chloride represses Mcl-1 protein via lysosomal degradation in oral squamous cell carcinoma.

BACKGROUND: We have shown previously that nitidine chloride (NC) induces apoptosis via inhibition of signal transducer and activator of transcription 3 (STAT3). However, its downstream molecules are not fully understood yet. Here, we report that NC as STAT3 inhibitor downregulates myeloid cell leukemia-1 (Mcl-1) protein in HSC-3 and HSC-4 human oral squamous cell carcinoma (OSCC) cells and a nude mouse tumor xenograft model. METHODS: This study investigated the effects of NC on Mcl-1 expression in HSC-3 and HSC-4 cells using Western blotting, RT-PCR, and dual-luciferase assay. Immunohistochemistry was employed to evaluate Mcl-1 expression levels in mouse tumor tissues. Construction of Mcl-1 overexpression vector and transient transfection was done to test the apoptosis of HSC-3 cells. RESULTS: Nitidine chloride did not affect either mRNA level or promoter activity of Mcl-1, and the decrease in Mcl-1 protein by NC was caused by lysosome-dependent degradation, but not proteasome-dependent degradation. The overexpression of Mcl-1 protein in OSCC cell lines was sufficient to block the induction of apoptosis. In addition, NC strongly reduced the expression level of Mcl-1 protein compared with other STAT3 inhibitors such as cryptotanshione and S3I-201 in OSCCs. CONCLUSIONS: Our findings suggest that NC triggers apoptosis via lysosome-dependent Mcl-1 protein degradation and could be chosen as a promising chemotherapeutic candidate against human OSCCs.

Apoptosis induced by methanol extract of Potentilla discolor in human mucoepidermoid carcinoma cells through STAT3/PUMA signaling axis.

Potentilla discolor has been used in traditional Chinese medicine for the treatment of hyperglycemia. However, the potential role of Potentilla discolor against cancer and its mode of action remain to be fully elucidated. The present study explored the apoptotic effect of methanol extract of Potentilla discolor (MEPD) in human mucoepidermoid carcinoma (MEC) cell lines of salivary glands. MEPD markedly suppressed the growth and induced apoptotic cell death in MC3 and YD15 cells. MEPD treatment significantly upregulated the expression of PUMA and reduced STAT3 phosphorylation. Overexpression of STAT3 partially recovered the growth of MEC cells inhibited by MEPD. In addition, dephosphorylation of STAT3 by cryptotanshinone (a potent STAT3 inhibitor) was sufficient to inhibit the growth of MEC cells and induce apoptosis via affecting PUMA protein. These results suggest that MEPD has a potential anticancer property via the STAT3/PUMA signaling axis in human MEC cells of salivary gland.

Nitidine chloride acts as an apoptosis inducer in human oral cancer cells and a nude mouse xenograft model via inhibition of STAT3.

Nitidine chloride (NC) is a natural alkaloid compound derived from the plant Zanthoxylum nitidum and is known for its therapeutic anticancer potential. In this study, we investigated the effects of NC on growth and signaling pathways in human oral cancer cell lines and a tumor xenograft model. The apoptotic effects and related molecular targets of NC on human oral cancer were investigated using trypan blue exclusion assay, DAPI staining, Live/Dead assay, Western blotting, Immunohistochemistry/Immunofluorescence and a nude mouse tumor xenograft. NC decreased cell viability in both HSC3 and HSC4 cell lines; further analysis demonstrated that cell viability was reduced via apoptosis. STAT3 was hyper-phosphorylated in human oral squamous cell carcinoma (OSCC) compared with normal oral mucosa (NOM) and dephosphorylation of STAT3 by the potent STAT3 inhibitor, cryptotanshinone or NC decreased cell viability and induced apoptosis. NC also suppressed cell viability and induced apoptosis accompanied by dephosphorylating STAT3 in four other oral cancer cell lines. In a tumor xenograft model bearing HSC3 cell tumors, NC suppressed tumor growth and induced apoptosis by regulating STAT3 signaling without liver or kidney toxicity. Our findings suggest that NC is a promising chemotherapeutic candidate against human oral cancer.

Oridonin induces apoptosis in human oral cancer cells via phosphorylation of histone H2AX.

Oridonin, a natural diterpenoid purified from Rabdosia rubescens, has displayed beneficial biological activities, including anti-proliferation and anti-angiogenesis effects, in various types of cancers. However, the anti-cancer potential of oridonin and its mechanism in oral cancer have never previously been studied. In this study, we assessed the role of oridonin as an inducer of apoptosis in HSC-3 and HSC-4 human oral cancer cells. Our results showed that oridonin reduces the viability of human oral cancer cells and significantly increases the expression of γH2AX, a well-known marker of DNA damage. 4',6-Diamidino-2-phenylindole (DAPI) staining and western blotting showed that oridonin causes nuclear condensation and fragmentation, and induces cleavage of poly(ADP-ribose) polymerase (PARP). Moreover, oridonin-induced γH2AX accumulation was partially abrogated by Z-VAD, a pan-caspase inhibitor. Taken together, our results suggest that oridonin can effectively induce apoptosis by augmenting the expression of γH2AX in response to DNA damage and might be a promising anti-cancer drug candidate for the treatment of oral cancer.

Apoptosis induced by caffeic acid phenethyl ester in human oral cancer cell lines: Involvement of Puma and Bax activation.

OBJECTIVE: Caffeic acid phenethyl ester (CAPE), a natural honeybee product exhibits a spectrum of biological activities including antimicrobial, anti-inflammatory, antioxidant and antitumor actions. The purpose of this research was to investigate the anticancer potential of CAPE and its molecular mechanism in human oral cancer cell lines (YD15, HSC-4 and HN22 cells). DESIGN: To determine the apoptotic activity of CAPE and identify its molecular targets, trypan blue exclusion assay, soft agar assay, Western blot analysis, DAPI staining, and live/dead assay were performed. RESULTS: CAPE significantly suppressed transformation of neoplastic cells induced by epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol 13-acetate (TPA) without inhibiting growth. CAPE treatment inhibited cell growth, increased the cleavages of caspase-3 and poly (ADP-ribose) polymerase (PARP), and augmented the number of fragmented nuclei in human oral cancer cell lines. CAPE activated Bax protein causing it to undergo a conformational change, translocate to the mitochondrial outer membrane, and oligomere. CAPE also significantly increased Puma expression and interestingly Puma and Bax were co-localized. CONCLUSION: Overall, these results suggest that CAPE is a potent apoptosis-inducing agent in human oral cancer cell lines. Its action is accompanied by up-regulation of Bax and Puma proteins.

Silymarin and its active component silibinin act as novel therapeutic alternatives for salivary gland cancer by targeting the ERK1/2-Bim signaling cascade.

PURPOSE: Approximately 20% of all salivary gland cancer patients who are treated with current treatment modalities will ultimately develop metastases. Its most common form, mucoepidermoid carcinoma (MEC) is a highly aggressive tumor with an overall 5-year survival rate of ~30%. Until now, several chemotherapeutic drugs have been tested for the treatment of salivary gland tumors, but the results have been disappointing and the drugs often cause unwanted side effects. Therefore, several recent studies have focused on the potential of alternative and/or complementary therapeutic options, including the use of silymarin. METHODS: The effects of silymarin and its active component silibinin on salivary gland cancer-derived MC3 and HN22 cells and their underlying molecular mechanisms were examined using trypan blue exclusion, 4'-6-diamidino-2-phenylindole (DAPI) staining, Live/Dead, Annexin V/PI staining, mitochondrial membrane potential (ΔΨm) measurement, quantitative RT-PCR, soft agar colony formation and Western blotting analyses. RESULTS: We found that silymarin and silibinin dramatically increased the expression of the pro-apoptotic protein Bim in a concentration- and time-dependent manner and, concomitantly, induced apoptosis in MC3 and HN22 cells. We also found that ERK1/2 signaling inhibition successfully sensitized these cells to the apoptotic effects of silymarin and silibinin, which indicates that the ERK1/2 signaling pathway may act as an upstream regulator that modulates the silymarin/silibinin-induced Bim signaling pathway. CONCLUSIONS: Taken together, we conclude that ERK1/2 signaling pathway inhibition by silymarin and silibinin increases the expression of the pro-apoptotic Bcl-2 family member Bim which, subsequently, induces mitochondria-mediated apoptosis in salivary gland cancer-derived cells.

Sorafenib potentiates ABT-737-induced apoptosis in human oral cancer cells.

OBJECTIVE: The mimetic BH3 ABT-737, a potent inhibitor of anti-apoptotic Bcl-2 family proteins, has potential as anti-cancer drug in many cancers. Recently, patients treated with ABT-737 have developed drug tolerance during cancer therapy. Therefore, we examined whether ABT-737 is effective in killing MC-3 and HSC-3 human oral cancer cells either alone or in combination with the oncogenic kinase inhibitor, sorafenib. DESIGN: The potentiating activities of sorafenib in ABT-737-induced apoptosis were determined using trypan blue exclusion assay, DAPI staining, cell viability assay and Western blot analysis. RESULTS: Combined use of ABT-737 and sorafenib synergistically suppressed cell viability and induced apoptosis compared with either compound individually. The combination of ABT-737 and sorafenib altered only Bax and Bak proteins and their activations, resulting in mitochondrial translocation of Bax from the cytosol. Additionally, combination treatment-mediated apoptosis may be correlated with ERK and STAT3 pathways. CONCLUSIONS: These results suggest that sorafenib may effectively overcome ABT-737 resistance to apoptotic cell death, which can be a new potential chemotherapeutic strategy against human oral cancer.

Growth-suppressive effect of suberoylanilide hydroxamic acid (SAHA) on human oral cancer cells.

PURPOSE: The histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) has been reported to exhibit anticancer activities in various cancer cell types, but as yet there are few reports on the anticancer effects of SAHA in oral squamous cell carcinoma (OSCC)-derived cells and xenograft models. METHODS: The anti-proliferative and apoptotic activities of SAHA were assessed in human HSC-3 and HSC-4 (OSCC)-derived cell lines and JB6 normal mouse skin-derived epidermal cells using histone acetylation, soft agar colony formation, trypan blue exclusion, 4'-6-diamidino-2-phenylindole (DAPI) staining, Live/Dead viability/cytotoxicity and Western blot analyses. RESULTS: We found that SAHA treatment resulted in hyperacetylation of histones H2A and H3 and a concomitant decrease in the viability of HSC-3 and HSC-4 cells. SAHA also significantly inhibited the neoplastic transformation of JB6 cells treated with TPA, whereas the viability of these cells was not affected by this treatment. Additionally, we found that SAHA suppressed the anchorage-independent growth (colony forming capacity in soft agar) of HSC-3 and HSC-4 cells. DAPI staining, Live/Dead and Western blot analyses revealed that SAHA can induce caspase-dependent apoptosis in HSC-3 and HSC-4 cells. We also found that SAHA treatment led to inhibition of ERK phosphorylation, and that two MEK inhibitors potentiated SAHA-mediated apoptosis. Okadaic acid treatment inhibited SAHA-mediated apoptosis in both the HSC-3 and HSC-4 cell lines, wheras SAHA induced a profound in vivo inhibition of tumor growth in HSC-3 xenografts. CONCLUSIONS: Our results indicate that the ERK signaling pathway may constitute a critical denominator of SAHA-induced apoptosis in OSCC-derived cells and that SAHA may have therapeutic potential for OSCC.

Inhibition of myeloid cell leukemia-1: Association with sorafenib-induced apoptosis in human mucoepidermoid carcinoma cells and tumor xenograft.

BACKGROUND: The purpose of our study was to investigate the anticancer effect of sorafenib on mucoepidermoid carcinoma (MEC) and find its new molecular mechanism. METHODS: The apoptotic effects of sorafenib were performed using MTS assay, diamidino-phenylindole (DAPI) staining, Western blotting, reverse transcription-polymerase chain reaction (RT-PCR), siRNA, and xenograft. RESULTS: Sorafenib had apoptotic effects on MC-3 and YD15 cells and decreased myeloid cell leukemia-1 (Mcl-1) through proteasome-dependent protein degradation and the inhibition of protein synthesis. Sorafenib significantly affected truncated bid (t-Bid) and siMcl-1 resulting in the upregulation of t-Bid to induce apoptosis. Signal transducer and activator of transcription 3 (STAT3) phosphorylation was also blocked by sorafenib and a potent STAT3 inhibitor, cryptotanshinone clearly induced poly ADP-ribose polymerase (PARP) cleavage by inhibiting Mcl-1 and increasing t-Bid. Finally, administration of sorafenib significantly suppressed tumor growth and induced apoptosis in tumor xenograft model in association with downregulation of Mcl-1 without any side effects. CONCLUSION: Taken together, these findings suggest that sorafenib can be a good anticancer drug candidate for the treatment of MEC.

Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer.

Cervical cancer is the third most common cancer and the third leading cause of death among women. However, the standard treatment for cervical cancer includes cisplatin, which can cause side effects such as hematological damage or renal toxicity. New innovations in cervical cancer treatment focus on developing more effective and better-tolerated therapies such as Sp1-targeting drugs. Previous studies suggested that mithramycin A (Mith) inhibits the growth of various cancers by decreasing Sp1 protein. However, how Sp1 protein is decreased by Mith is not clear. Few studies have investigated the regulation of Sp1 protein by proteasome-dependent degradation as a possible control mechanism for the regulation of Sp1 in cancer cells. Here, we show that Mith decreased Sp1 protein by inducing proteasome-dependent degradation, thereby suppressing cervical cancer growth through a DR5/caspase-8/Bid signaling pathway. We found that prolonged Mith treatment was well tolerated after systemic administration to mice carrying cervical cancer cells. Reduction of body weight was minimal, indicating that Mith was a good therapeutic candidate for treatment of cancers in which Sp1 is involved in promoting and developing disease.

Signal transducer and activators of transcription 3 regulates cryptotanshinone-induced apoptosis in human mucoepidermoid carcinoma cells.

BACKGROUND: Cryptotanshinone (CT) is a biologically active compound from the root of Salvia miltiorrhiza that has been reported to induce apoptosis in various cancer cell lines; but, it has not yet been fully explored in human mucoepidermoid carcinoma (MEC). OBJECTIVE: Here, we demonstrated the apoptotic effects and its related mechanism in MC-3 and YD-15 human MEC cell lines. MATERIALS AND METHODS: The effects of CT on apoptotic activity were evaluated by cell proliferation assay, Western blotting, 4'-6-diamidino-2-phenylindole staining, reverse transcription-polymerase chain reaction, and luciferase assay. RESULTS: Our data show that CT treatment of MC-3 cells results in anti-proliferative and apoptotic activities in MC-3 and it is accompanied by a decrease in phosphorylation and dimerization of signal transducer and activators of transcription 3 (STAT3). CT decreased the expression levels of myeloid cell leukemia-1 (Mcl-1) and surviving, whereas Bcl-xL expression was not changed. CT clearly regulates survivin protein at a transcriptional level and alters Mcl-1 through proteasome-dependent protein degradation. In addition, CT-induced apoptotic cell death in YD-15, another human MEC cell line, was associated with the inhibition of STAT3 phosphorylation. CONCLUSION: These data suggest that CT could be a good apoptotic inducer through modification of STAT3 signaling in human MEC cell lines.

Intraosseous pseudocarcinomatous hyperplasia associated with chronic osteomyelitis of the mandible: report of two cases.

Pseudocarcinomatous hyperplasia (PH) is a marked proliferation of benign squamous epithelium lacking cytologic atypia and pleomorphism in response to chronic stimuli, such as inflammation, infection, irradiation, or an underlying neoplastic reaction. Intraosseous PH is a rare complication of chronic osteomyelitis and mimics squamous cell carcinoma and other squamous neoplasms. This report describes 2 cases of intraosseous PH arising in the mandible.

Apoptotic effect of methanol extract of Picrasma quassioides by regulating specificity protein 1 in human cervical cancer cells.

In the present study, we examined the effects of methanol extracts of Picrasma quassioides (MEPQ) on apoptosis in human cervical cancer cells. The results showed that MEPQ decreased the viability and induced caspase-dependent apoptosis in HEp-2 cells. MEPQ decreased specificity protein 1 (Sp1) in HEp-2 cells, whereas Sp1 mRNA was not changed. We found that MEPQ reduced Sp1 protein through proteasome-dependent protein degradation, but not the inhibition of protein synthesis. Also, MEPQ increased the expressions of Bad and truncated Bid (t-Bid) but did not alter other Bcl-2 family members. The knock-down of Sp1 by both Sp1 interfering RNA and Mithramycin A, Sp1 specific inhibitor clearly increased Bad and t-Bid expression to decrease cell viability and induce apoptosis. In addition, MEPQ inhibited cell viability and induced apoptotic cell death through the modulation of Sp1 in KB cells. These results suggest that MEPQ may be a potential anticancer agent for human cervical cancer.

Fucoidan induces caspase-dependent apoptosis in MC3 human mucoepidermoid carcinoma cells.

Fucoidan is a sulfated polysaccharide present in brown algae that has been identified to exhibit multiple biological effects. In this study, the apoptotic effects of fucoidan in MC3 human mucoepidermoid carcinoma (MEC) cells were investigated. The apoptotic effects of fucoidan on MC3 MEC cells were evaluated by cell proliferation assay, 4',6-diamidino-2-phenylindole staining and western blot analysis. The results showed that fucoidan decreased cell proliferation and induced caspase-dependent apoptosis in MC3 MEC cells. Fucoidan downregulated the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, whereas phospho-p38 mitogen-activated protein kinase or phospho-c-Jun NH2-terminal kinase (JNK) levels were not altered. In addition, fucoidan significantly decreased the expression levels of myeloid cell leukemia-1 (Mcl-1). These results suggest that fucoidan is able to modulate the ERK1/2 pathway and thereby regulate Mcl-1 protein expression and induce apoptosis in MC3 MEC cells. Therefore, fucoidan may be a promising agent for the treatment of human MEC.