• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.439-446
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• 2022

The antitumoral effects of valdecoxib (Val), an United States Food and Drug Administration-approved anti-inflammatory drug that was withdrawn due to the side effects of increased risk of cardiovascular adverse events, were investigated in hypopharyngeal squamous cell carcinoma cells by performing a cell viability assay, transwell assay, immunofluorescence imaging, and Western blotting. Val markedly inhibited cell viability with an IC50 of 67.3 µM after 48 h of treatment, and also downregulated cell cycle proteins such as Cdks and their regulatory cyclin units. Cell migration and invasion were severely suppressed by inhibiting integrin α4/FAK expression. In addition, Val activated the cell cycle checkpoint CHK2 in response to excessive DNA damage, which led to the activation of caspase-3/9 and induced caspase-dependent apoptosis. Furthermore, the signaling cascades of the PI3K/AKT/mTOR and mitogen-activated protein kinase pathways were significantly inhibited by Val treatment. Taken together, our results indicate that Val can be used for the treatment of hypopharyngeal squamous cell carcinoma.

• International Journal of Oral Biology
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• v.45 no.4
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• pp.218-224
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• 2020

The antitumor effects of octyl gallate (OG) were investigated on FaDu human hypopharyngeal squamous carcinoma cells. At various concentrations, OG inhibited the proliferation of FaDu cells by suppressing cell cycle regulators and induced apoptosis by activating caspase 3 and its downstream poly (ADP-ribose) polymerase, thereby damaging DNA. Immunoblotting demonstrated that OG significantly suppressed the expression of integrin family proteins (integrin α4, αv, β3, β4), hindering cell adhesion. The reduced expression of integrins subsequently mediated the mitogen-activated protein kinase signaling pathway to stimulate the activation of extracellular signal-regulated kinases and c-jun N-terminal kinases, leading to apoptosis. Thus, OG demonstrated antitumor activity on hypopharyngeal squamous carcinoma cells by suppressing cell proliferation and inducing apoptosis.

• Korean Journal of Head & Neck Oncology
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• v.15 no.1
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• pp.18-21
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• 1999

Background and Objectives: Occult neck metastasis rate of laryngeal and hypopharyngeal cancer varies widely depending upon authors. Materials and Methods: Sixty four cases, previously untreated, of N0 laryngeal and hypopharyngeal squamous cell carcinoma patients who underwent surgery as an initial treatment from 1992 to 1997 were evaluated. All had unilateral or bilateral elective neck dissection at the time of surgery for the primary. Occult neck metastasis rate was evaluated with pathologic examination of neck dissection specimen. Results: Occult neck metastasis rate by primary site was as follows. Supraglottis ipsilateral 32%(8/25) contralateral 15%(3/20), glottis ipsilateral 17%(5/30), contralateral 0%(0/22), hypopharynx ipsilateral 78%(7/9), contralateral 25%(2/8). Conclusion: Supraglottic and hypopharyngeal cancer may need elective neck treatment bilaterally. Occult neck metastasis of glottic cancer to opposite site was minimal.

• Clinical Endoscopy
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• v.56 no.3
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• pp.315-324
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• 2023

Background/Aims: Image-enhanced endoscopy can detect superficial oro-hypopharyngeal squamous cell carcinoma; however, reliable endoscopy of the pharyngeal region is challenging. Endoscopy under general anesthesia during transoral surgery occasionally reveals multiple synchronous lesions that remained undetected on preoperative endoscopy. Therefore, we aimed to determine the lesion detection capability of endoscopy under general anesthesia for superficial oro-hypopharyngeal squamous cell carcinoma. Methods: This retrospective study included 63 patients who underwent transoral surgery for superficial oropharyngeal squamous cell carcinoma between April 2005 and December 2020. The primary endpoint was to compare the lesion detection capabilities of preoperative endoscopy and endoscopy under general anesthesia. Other endpoints included the comparison of clinicopathological findings between lesions detected using preoperative endoscopy and those newly detected using endoscopy under general anesthesia. Results: Fifty-eight patients (85 lesions) were analyzed. The mean number of lesions per patient detected was 1.17 for preoperative endoscopy and 1.47 for endoscopy under general anesthesia. Endoscopy under general anesthesia helped detect more lesions than preoperative endoscopy did (p<0.001). The lesions that were newly detected on endoscopy under general anesthesia were small and characterized by few changes in color and surface ruggedness. Conclusions: Endoscopy under general anesthesia for superficial squamous cell carcinoma is helpful for detecting multiple synchronous lesions.

• International Journal of Oral Biology
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• v.44 no.2
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• pp.43-49
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• 2019

Tannic acid (TA) is a water-soluble polyphenol compound found in various herbal plants. We investigated the chemopreventive effects of TA on FaDu hypopharyngeal squamous carcinoma cells. In an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, TA showed dose-dependent cytotoxicity with a half maximal inhibitory concentration (IC50) of 50 ?M. Cell cycle analysis and immunofluorescence imaging demonstrated that under low-dose ($25{\mu}M$) treatment, FaDu cells were arrested in G2/M phase, and as the dose of TA was increased, apoptosis was induced with the increase of cell population at sub-G1 phase. The expressions of various cyclins, including cyclin D1 and cyclin-dependent kinases (CDK-1 and CDK-2), were down-regulated at low doses of TA, whereas apoptotic effectors such as cleaved caspase 3, cleaved caspase 7, and poly (ADP-ribose) polymerase (PARP) were expressed in a dose-dependent manner in Western blotting. In addition, TA-induced apoptosis of FaDu cells might be mediated by the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase pathway, with the upregulation of p-AKT/p-PKB (phosphorylated protein kinase B) and p-ERK. Overall, our data support the hypothesis that TA is a potential candidate agent for the treatment of hypopharyngeal cancer.

• International Journal of Oral Biology
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• v.41 no.4
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• pp.183-190
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• 2016

Anthricin (Deoxypodophyllotoxin), a naturally occurring flavolignan, has well known anti-cancer properties in several cancer cells, such as prostate cancer, cervical carcinoma and pancreatic cancer. However, the effects of Anthricin are currently unknown in oral cancer. We examined the anticancer effect and mechanism of action of Anthricin in human FaDu hypopharyngeal squamous carcinoma cells. Our data showed that Anthricin inhibits cell viability in a dose- and time-dependent manner ($IC_{50}$ 50 nM) in the MTT assay and Live & Dead assay. In addition, Anthricin treated FaDu cells showed marked apoptosis by DAPI stain and FACS. Furthermore, Anthricin activates anti-apoptotic factors such as caspase-3, -9 and poly (ADP-ribose) polymerase (PARP), suggesting that caspase-mediated pathways are involved in Anthricin- induced apoptosis. Anthricin treatment also leads to accumulation of the pro-apoptotic factor Bax, followed by inhibition of cell growth. Taken together, these results indicate that Anthricn-induced cell death of human FaDu hypopharyngeal squamous carcinoma cells is mediated by mitochondrial-dependent apoptotic pathway. In summary, our findings provide a framework for further exploration on Anthricin as a novel chemotherapeutic drug for human oral cancer.

• 대한두경부종양학회:학술대회논문집
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• 2005.11a
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• pp.221-221
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• 2005

• International Journal of Oral Biology
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• v.43 no.2
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• pp.61-68
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• 2018

Codium fragile (Suringar) Hariot is an edible green seaweed that belong to the Codiaceae family and has been used in Oriental medicine for the treatment of enterobiasis, dropsy, and dysuria. Methanol extract of codium fragile has anti-oxidant, anti-inflammatory and anti-cancer properties, although the anti-cancer effect on oral cancer has not yet been reported. In this study, we investigated the anti-cancer activity and the mechanism of cell death by methanol extracts of Codium fragile (MeCF) on human FaDu hypopharyngeal squamous carcinoma cells. Our data showed that MeCF inhibits cell viability in a dose-dependent manner, and markedly induced apoptosis, as determined by the MTT assay, Live/Dead assay, and DAPI stain. In addition, MeCF induced the proteolytic cleavage of procaspase -3, -7, -9 and poly(ADP-ribose) polymerase(PARP), and upregulated or downregulated the expression of mitochondrial-apoptosis factor, Bax(pro-apoptotic factor), and Bcl-2(anti-apoptotic factor). Futhermore, MeCF induced a cell cycle arrest at the G1/S phase through suppressing the expression of the cell cycle cascade proteins, p21, CDK4, CyclinD1, and phospho-Rb. Taken together, these results indicated that MeCF inhibits cell growth, and this inhibition is mediated by caspase- and mitochondrial-dependent apoptotic pathways through cell cycle arrest at the G1/S phase in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, methanol extracts of Codium fragile can be provided as a novel chemotherapeutic drug due to its growth inhibition effects and induction of apoptosis in human oral cancer cells.

• International Journal of Oral Biology
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• v.46 no.4
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• pp.160-167
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• 2021

Nypa fruticans Wurmb (NFW) contains a large amount of phenolic acid and flavonoids, and is popular as a superfood in Myanmar. NFW has various biological activities, such as anti-inflammatory, anti-oxidant, and neuroprotective properties; however, the anti-cancer effect of NFW have not been reported. In this study, we investigated the anticancer activity of water extracts of NFW (WeNFW) and the underlying mechanism in human FaDu hypopharyngeal squamous carcinoma cells. The WeNFW inhibited FaDu cell growth in a dose-dependent manner without affecting normal cells (L929), as determined by an MTT assay and Live and Dead assay. In addition, the concentrations of WeNFW without cytotoxicity (0.025, 0.05, and 0.1 mg/mL) inhibited wound healing and colony formation. Furthermore, WeNFW significantly induced apoptosis through the proteolytic cleavage of caspase-3 and -9, poly (ADP-ribose) polymerase, and downregulation of Bcl-2 and upregulation of Bax in FaDu cells, as determined by DAPI staining, FACS analysis, and western blot analysis. Taken together, these results suggest that WeNFW exhibits potent anti-cancer effects by suppressing the growth of oral cancer cells, wound healing and colony formation activity. Via mitrochondrial-dependent apoptotic pathways in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, WeNFW can provide a natural chemotherapeutic drug for oral cancer in humans.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.821-825
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• 2012

Purpose: Centromere protein H (CENP-H) and Ki67 are overexpressed in some malignancies, but whether they are predictors of survival after primary resection for hypopharyngeal squamous cell carcinoma (HSCC) remains unknown. Methods: We assessed immunohistochemical expression of CENP-H and Ki67 in 112 HSCC specimens collected between March 2003 and March 2005 for analysis by clinical characteristics. The Kaplan-Meier method was used to analyze relapse-free survival and logistic multivariate regression to determine risk factors of relapse-free survival. Cholecystokinin octapeptide assays and flow cytometry were used to examine cell proliferation and apoptosis after siRNA inhibition of CENP-H in HSCC cells. Results: Overall, 50 (44.6%) HSCC specimens showed upregulated CENP-H expression and 69 (61.6%) upregulated Ki67. An increased CENP-H protein level was associated with advanced cancer stage and alcohol history (P=0.012 and P=0.048, respectively) but an increased Ki67 protein level only with advanced cancer stage (P=0.021). Increased CENP-H or Ki67 were associated with short relapse-free survival (P<0.001 or P=0.009, respectively) and were independent predictors of relapse-free survival (P=0.001 and P=0.018, respectively). siRNA knockdown of CENP-H mRNA inhibited cell proliferation and promoted cancer cell apoptosis in vitro. Conclusions: Upregulated CENP-H and Ki67 levels are significantly associated with short relapse-free survival in HSCC. These factors may be predictors of a relapsing phenotype in HSSC cases.