• International Journal of Oral Biology
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• v.46 no.2
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• pp.85-93
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• 2021

Asarum sieboldii Miq. (Aristolochiaceae) is a perennial herbaceous plant and has been used as traditional medicine for treating diseases, cold, fever, phlegm, allergies, chronic gastritis, and acute toothaches. Also, it has various biological activities, such as antiallergic, antiinflammatory, antinociceptive, and antifungal. However, the anticancer effect of A. sieboldii have been rarely reported, except anticancer effect on lung cancer cell (A549) of water extracts of A. sieboldii. This study investigated the anticancer activity of methanol extracts of A. sieboldii (MeAS) and the underlying mechanism in human FaDu hypopharyngeal squamous carcinoma cells. MeAS inhibited FaDu cells grown dose-dependently without affecting normal cells (L929), as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and live and dead assay. In addition, concentration of MeAS without cytotoxicity (0.05 and 0.1 mg/mL) inhibited migration and colony formation. Moreover, MeAS treatment significantly induced apoptosis through the proteolytic cleavage of caspase-3, -7, -9, poly (ADP-ribose) polymerase, and downregulation of Bcl-2 and upregulation of Bax in FaDu cells, as determined by fluorescence-activated cell sorting analysis, 4'6-diamidino-2-phenylindole stain, and western blotting. Altogether, these results suggest that MeAS exhibits strong anticancer effects by suppressing the growth of oral cancer cells and the migration and colony formation via caspase- and mitochondrial-dependent apoptotic pathways in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, MeAS can serve as a natural chemotherapeutic for human oral cancer.

• International Journal of Oral Biology
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• v.42 no.2
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• pp.47-54
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• 2017

Anthriscus sylvestris (L.) Hoffm. is a perennial herb found widely distributed in various regions of Korea, Europe, and New Zealand. The root of A. sylvestris have been extensively used in the treatment for antitussive, antipyretic, cough remedy in Oriental medicine, but the physiologically active function of the leaf of A. sylvestris is as yet unknown. In this study, we investigated the anti-cancer activity and the mechanism of cell death of water extracts of leaf of Anthriscus sylvestris (WELAS), on human FaDu hypopharyngeal squamous carcinoma cells. Our data showed that WELAS treatment inhibited cell viability in a concentration- and time-dependent manner. In addition, the treatment of WELAS markedly induced apoptosis in FaDu cells, as determined by the viability assay, DAPI stain and FACS analysis. WELAS also increased the proteolytic cleavage of procaspase-3, -9 and PARP (poly(ADP-ribose) polymerase). In addition, exposure to WELAS decreased the expression of Bcl-2 (an anti-apoptotic factor), but increased the expression of Bax (a pro-apoptotic factor), suggesting that mitochondria-dependent apoptotic pathways are mediated in WELAS-induced apoptosis. Taken together, these results indicate that water extracts of leaf of A. sylvestris inhibits cell growth and induces apoptosis via the mitochondrial-dependent apoptotic pathway in FaDu human hypopharyngeal squamous carcinoma cells. Therefore, we propose that the water extracts of leaf of A. sylvestris is a novel chemotherapeutic drug, having growth inhibitory properties and induction of apoptosis in human oral cancer cells.

• International Journal of Oral Biology
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• v.45 no.3
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• pp.99-106
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• 2020

Ficus carica L. (fig) is one of the first cultivated crops and is as old as humans. This plant has been extensively used as a traditional medicine for treating diseases, such as cough, indigestion, nutritional anemia, and tuberculosis. However, the physiological activity of fig leaves on oral cancer is as yet unknown. In this study, we investigated the anticancer effect of methanol extracts of Ficus carica (MeFC) and the mechanism of cell death in human FaDu hypopharyngeal squamous carcinoma cells. MeFC decreased the viability of oral cancer (FaDu) cells but did not affect the viability of normal (L929) cells, as determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay and Live and Dead assay. In addition, MeFC induced apoptosis through the proteolytic cleavage of procaspase-3, -9, poly (ADP-ribose) polymerase (PARP), downregulation of Bcl-2, and upregulation of Bax, as determined by 4′,6-diamidino-2-phenylindole dihydrochloride staining and western blot analysis. Moreover, a concentration of MeFC without cytotoxicity (0.25 mg/mL) significantly suppressed colony formation, a hallmark of cancer development, and completely inhibited the colony formation at 1 mg/mL. Collectively, these results suggest that MeFC exhibits a potent anticancer effect by suppressing the growth of oral cancer cells and colony formation via caspase- and mitochondrial-dependent apoptotic pathways in FaDu human hypopharyngeal squamous carcinoma cells. Therefore, the methanol extract of Ficus carcica leaves provide a natural chemotherapeutic drug for human oral cancer.

• International Journal of Oral Biology
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• v.44 no.3
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• pp.81-88
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• 2019

Trifolium pratense leaves (red clover) has been used in Oriental and European folk medicine for the treatment of whooping cough, asthma, and eczema, and is now being used to treat and alleviate the symptoms, such as hot flushes, cardiovascular health effects that occur in postmenopausal women. However, relatively little scientific data is available on the physiological activity of this plant. Therefore, in this study, we investigated the anti-cancer activity of T. pratense leaves using methanol extract of T. pratense leaves (MeTP) on human FaDu hypopharyngeal squamous carcinoma cells. MeTP inhibited the viability of FaDu cells by inducing apoptosis through the cleavage of procaspase-3, -7, and -9 and poly (adenosine diphosphate ribose-ribose) polymerase (PARP), downregulation of Bcl-2, and upregulation of Bax, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Live & dead assay, 4'6-diamidino-2-phenylindole stain, fluorescence-activated cell sorting analysis, and Western blot analysis. In addition, colony formation was slightly inhibited when FaDu cells were treated with a non-cytotoxic concentration (0.125 mg/mL) of MeTP and almost completely inhibited when cells were treated with 0.25 mg/mL MeTP. Collectively, these results indicate that MeTP induced cell apoptosis via caspase- and mitochondrial-dependent apoptotic pathways, and inhibited colony formation of cancer cells in FaDu human hypopharyngeal squamous carcinoma cells. These findings suggest MeTP should be considered for clinical development as a chemotherapeutic option in oral cancer.

• International Journal of Oral Biology
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• v.47 no.1
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• pp.9-15
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• 2022

Humulus japonicus (HJ) is a widely used herbal medicine for pulmonary tuberculosis, hypertension, leprosy, and venomous wounds in Asia, particularly in China. Although HJ has certain physiological activities, such as longitudinal bone growth, antioxidation and alleviation of rheumatism, its anticancer activities, other than in colorectal and ovarian cancer, are yet to be studied. In this study, we investigated the anti-cancer activity and mechanism of methanol extracts of HJ (MeHJ) against human FaDu hypopharyngeal squamous carcinoma cells. MeHJ suppressed FaDu cell viability without affecting normal cells (L929), which was demonstrated using the MTT and Live & Dead assays. Furthermore, MeHJ effectively inhibited colony formation of FaDu cells, even at non-cytotoxic concentrations, and significantly induced apoptosis through the proteolytic cleavage of caspase-9, -3, -7, poly (ADP-ribose) polymerase and through the downregulation of BCL-2 and upregulation of BAX in FaDu cells, as determined by DAPI staining, flow cytometry, and western blot analyses. Collectively, these findings suggest that the inhibitory effects of MeHJ on the growth and colony formation of oral cancer cells may be mediated by caspase- and mitochondrial-dependent apoptotic pathways in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, MeHJ has the potential to be used as a natural chemotherapeutic drug against human oral cancer.

• International Journal of Oral Biology
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• v.47 no.3
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• pp.41-48
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• 2022

Ulva compressa Linnaeus (UCL) is a green algae seaweed that performs photosynthesis and is used as a food material in some Asian regions including Korea. It is known to be the dominant species in copper ion-contaminated seas, and many studies on copper ion resistant mechanisms have been reported. UCL is known to have an excellent antioxidant effect, but limited information is available regarding its other physiological activities. In this study, we investigated the anticancer activity of 30% prethanol extracts of Ulva compressa Linnaeus (30% PeUCL) and the underlying mechanisms of its activity on human FaDu hypopharyngeal squamous carcinoma cells. The 30% PeUCL extracts suppressed FaDu cell viability without affecting normal cells (L929), as determined by MTT and viability assays. Furthermore, the 30% PeUCL extracts induced apoptosis, as determined by DAPI staining. The 30% PeUCL extracts inhibited colony formation effectively as well as wound-healing of FaDu cells, even at noncytotoxic concentrations. In addition, 30% PeUCL extracts induced apoptosis significantly through proteolytic cleavage of caspase-3, -7, and -9, and poly (ADP-ribose) polymerase, and by downregulation of Bcl-2 and upregulation of Bax in FaDu cells, as determined by Western blot analysis. Collectively, these results suggest that the inhibitory effect of 30% PeUCL extracts on the growth of oral cancer cells, colony formation and wound-healing may be mediated by caspase- and mitochondrial-dependent apoptotic pathways in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, 30% PeUCL extracts can be administered as a natural chemotherapeutic drug for the treatment of human oral cancers.

• Archives of Plastic Surgery
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• v.42 no.5
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• pp.608-613
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• 2015

Background The purpose of this study was to compare postoperative morbidities and functional outcomes of pectoralis major myocutaneous (PMMC) flap and cutaneous free flap reconstruction approaches in hypopharyngeal squamous cell carcinoma patients. Methods We retrospectively reviewed records from 99 patients who underwent hypopharyngeal reconstruction with a cutaneous free flap (n=85) or PMMC flap (n=14) between 1995 and 2013. Morbidity was classified into hospitalization, medical, or flap-related complications. Functional outcomes were classified into oral re-alimentation and decannulation time. Results The overall flap-related complication rate was higher in the PMMC flap group (n=8, 57.1%; P=0.019), but the medical morbidity rate was higher in the cutaneous free flap group (n=68, 80%; P=0.006). The rate of pneumonia was higher in the cutaneous free flap group (n=48, 56.5%; P=0.020). Pulmonary premorbidity was the variable most significantly associated with pneumonia (odds ratio=3.012, P=0.012). There was no statistically significant difference in oral re-alimentation and decannulation time between the two groups. Conclusions Although the functional superiority of free flaps has been reported in many studies, our results do not support this hypothesis. One limitation of our study is the relatively smaller flap size and fewer PMMC flap cases compared with the cutaneous free flap group. The low postoperative medical morbidity incidence rate in the PMMC flap group was clinically significant; however, the free flap group had more flap-related complications. Thus, PMMC flaps should be considered a viable option, especially for patients with pulmonary premorbidities.

• Korean Journal of Head & Neck Oncology
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• v.18 no.1
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• pp.41-45
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• 2002

Background and Objectives: To evaluate the efficacy of the neoadjuvant chemotherapy and radiation therapy in treatment of patients with advanced hypopharyngeal cancer, which is notorious for its poor prognosis and severe surgical morbidity with functional deficits. Materials and Methods: Medical records and radiologic findings of 107 patients with squamous cell carcinoma of the hypopharynx, Stage III or IV (AJCC, 1997), were retrospectively reviewed. Results: Neoadjuvant chemotherapy followed by radiation therapy showed 74% complete remission (CR) rate. The patients who did not show CR after chemotherapy had a high likelihood of treatment failure, even though they achieved CR following subsequent radiotherapy. Twenty-eight of 57 patients were able to preserve their larynges for more than three years by chemotherapy and radiation. Conclusions: This approach appeared to be as effective as radical surgery with postoperative radiation therapy without comprising of survival. To improve the cure rates, we need to develop better strategies to increase CR rates with chemotherapy and determine the best treatment option for patients who are partially or nonresponsive to chemotherapy.

• Korean Journal of Radiology
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• v.22 no.4
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• pp.596-603
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• 2021

Objective: To evaluate the feasibility and diagnostic performance of ultrasound (US)-guided fine-needle aspiration cytology and core-needle biopsy (US-FNAC/CNB) for the diagnosis of laryngo-hypopharyngeal masses. Materials and Methods: This was a single-center prospective case series. From January 2018 to June 2019, we initially enrolled 40 patients with highly suspicious laryngo-hypopharyngeal masses on laryngoscopic examinations. Of these, 28 patients with the mass involving or abutting the pre-epiglottic, paraglottic, pyriform sinus, and/or subglottic regions were finally included. These patients underwent US examinations with/without subsequent US-FNAC/CNB under local anesthesia for evaluation of the laryngo-hypopharyngeal mass. Results: Of the 28 patients who underwent US examinations, a laryngo-hypopharyngeal mass was identified in 26 patients (92.9%). US-FNAC/CNB was performed successfully in 25 of these patients (96.2%), while the procedure failed to target the mass in 1 patient (3.8%). The performance of US caused minor subclinical hematoma in 2 patients (7.7%), but no major complications occurred. US-FNAC/CNB yielded conclusive results in 24 (96.0%) out of the 25 patients with a successful procedure, including 23 patients with squamous cell carcinoma (SCC) and 1 patient with a benign mass. In one patient with atypical cells in US-FNAC, additional direct laryngoscopic biopsy (DLB) was required to confirm SCC. Among the 26 patients who received US-FNAC/CNB, the time from first visit to pathological diagnosis was 7.8 days. For 24 patients finally diagnosed with SCC, the time from first visit to the initiation of treatment was 25.2 days. The mean costs associated with US-FNAC/CNB was $272 under the Korean National Health Insurance Service System. Conclusion: US-FNAC/CNB for a laryngo-hypopharyngeal mass is technically feasible in selected patients, providing good diagnostic performance. This technique could be used as a first-line diagnostic modality by adopting appropriate indications to avoid general anesthesia and DLB-related complications.

• Journal of Chest Surgery
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• v.24 no.8
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• pp.807-813
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• 1991

Between October 1987 and October 1990, 6 patients underwent pharyngolaryngoesophagectomy with transhiatal gastric transposition and pharyngogastrostomy for hypopharyngeal and recurred laryngeal cancer. All patients had squamous cell carcinoma and were male, with age range from 54 to 67 years. Two patients had been treated initially by chemotherapy, but the tumor had persisted. One patient had been treated by radiotherapy and operation, but tumor had recurred in hypopharynx. There was no operative death. Major complications were anastomotic leakage in three cases, wound disruption in four cases and one postoperative bleeding. Anastomotic leakage was recovered in two cases with conservative management. The average hospital day was 33 days postoperatively. We conclude that reconstruction of the pharynx and cervical esophagus with gastric transposition is one of the recommendable procedures for extensive resection of pharynx or cervical esophagus with acceptable morbidity and functional recovery.