• Journal of dental hygiene science
• /
• v.15 no.6
• /
• pp.794-799
• /
• 2015

In recent years, there has been a global trend toward the importance of natural extracts for the prevention and treatment of human diseases. ${\beta}$-glucan is known to have anti-inflammatory activity, anti-cancer, and improvement of immune system. Polycan is purified ${\beta}$-glucan from Aureobasidum pullulans SM-2001. The anti-cancer effects of ${\beta}$-gluconsan calcium, polycan and calcium gluconate complex, were evaluated in human oral cancer YD-10B cells. YD-10B cells were cultured in the presence of 0, 0.5, 0.75, 1 mg/ml ${\beta}$-gluconsan calcium for 48 hours. MTT assay, cell counting, and observation of cell morphology were conducted. The number of cells decreased and cell morphology changed in the 0.5 mg/ml of ${\beta}$-gluconsan calcium. Almost all cells were dead in the 0.75 and 1 mg/ml. MTT assay showed a dose-dependent reduction in cell proliferation (p<0.05). These results indicate that ${\beta}$-gluconsan calcium exhibiting anti-cancer effects in YD-10B cells through changes in cell morphology and cell death.

• Tuberculosis and Respiratory Diseases
• /
• v.85 no.2
• /
• pp.147-154
• /
• 2022

Background: The expression of calcium signaling pathway molecules is altered in various carcinomas, which are related to the proliferation and altered characteristics of cancer cells. However, changes in calcium signaling in anti-cancer drug-resistant cells (bearing a T790M mutation in epidermal growth factor receptor [EGFR]) remain unclear. Methods: Afatinib-mediated changes in the level of store-operated Ca²⁺ entry (SOCE)-related proteins and intracellular Ca²⁺ level in non-small cell lung cancer cells with T790M mutation in the EGFR gene were analyzed using western blot and ratiometric assays, respectively. Afatinib-mediated autophagic flux was evaluated by measuring the cleavage of LC3B-II. Flow cytometry and cell proliferation assays were conducted to assess cell apoptosis and proliferation. Results: The levels of SOCE-mediating proteins (ORAI calcium release-activated calcium modulator 1 [ORAI1], stromal interaction molecule 1 [STIM1], and sarco/endoplasmic reticulum Ca²⁺ ATPase [SERCA2]) decreased after afatinib treatment in non-small cell lung cancer cells, whereas the levels of SOCE-related proteins did not change in gefitinib-resistant non-small cell lung cancer cells (PC-9/GR; bearing a T790M mutation in EGFR). Notably, the expression level of SOCE-related proteins in PC-9/GR cells was reduced also responding to afatinib in the absence of extracellular Ca²⁺. Moreover, extracellular Ca²⁺ influx through the SOCE was significantly reduced in PC-9 cells pre-treated with afatinib than in the control group. Additionally, afatinib was found to decrease the level of SOCE-related proteins through autophagic degradation, and the proliferation of PC-9GR cells was significantly inhibited by a lack of extracellular Ca²⁺. Conclusion: Extracellular Ca²⁺ plays important role in afatinib-mediated autophagic degradation of SOCE-related proteins in cells with T790M mutation in the EGFR gene and extracellular Ca²⁺ is essential for determining anti-cancer drug efficacy.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.1
• /
• pp.281-285
• /
• 2013

Purpose: To probe the role of FasL in cell apoptosis in oral squamous cell carcinomas (OSCCs). Methods: The expression of Fas/FasL was assessed in 10 cases of normal oral epithelium, 38 cases of OSCC and tumor infiltrating lymphocytes (TIL), and 11 cases of metastatic lymph nodes by immunohistochemistry. Apoptosis of tumor cells and TIL was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). FasL-induction of T cell apoptosis was tested by co-culture assay in vitro with SCC-9 and Jurkat T cells. Results: The 10 cases of normal oral epithelium all demonstrated extensive expression of Fas, the positive rate being largely down-regulated in OSCC (21/38) (P<0.05) compared to the normal (10/10). At the same time, the positive rate of FasL significantly increased in OSCC (P<0.05) especially those with lymph node metastasis (P<0.05). The positive rates of Fas in well and middle differentiated OSCC were higher than those in poor differentiated OSCC (P<0.05). The AI of tumor cells in Fas-positive OSCC was remarkably higher than that in Fas-negative OSCC (P<0.01), with a positive correlation between Fas expression and cell differentiation as well as apoptosis (r=0.68, P<0.01). The AI of tumor cells in FasL positive OSCC was remarkably lower than that in control while the AI of TIL was higher than in FasL negative OSCC (P<0.05). The AI of tumor cells reversely correlated with that of TIL (r = -0. 72, P<0.05). It was found that SCC-9 cells expressing functional FasL could induce apoptosis of Jurkat cells as demonstrated by co-culture assays. As a conclusion, it is evident that OSCC cells expressing FasL can induce apoptosis in Fas-expressing T cells. Conclusions: In progression of OSCC, expression of the Fas/FasL changes significantly. The results suggest that FasL is a mediator of immune privilege in OSCC and may serve as an marker for predicting malignant change in oral tissues.

• International Journal of Oral Biology
• /
• v.32 no.3
• /
• pp.93-101
• /
• 2007

Cell behavior of the transformed cells is known to affect by interaction with extracellular matrix (ECM) proteins and integrin. To investigate the alterations of both integrin expression and cell-matrix interaction during neoplastic conversion of human oral kerationcytes, we studied expression levels of integrin subunits by flow cytometry and cellular responses to the ECM proteins in normal human oral keratinocytes (NHOKs), HPV-immortalized HOK-16B line, and three oral cancer cell lines established from HOK-16B line, CTHOK-16B-BaP, CTHOK-16B-DMBA, and CTHOK-16B-Dexa lines. The expression levels of ${\alpha}\;and\;{\beta}$ integrin subunits were shown decreased tendency in human oral keratinocytes undergoing immortalization and tumorigenic transformation except CTHOK-16B-DMBA line tested. Although ${\alpha}v{\beta}6$ integrin is known to be highly expressed in squamous cell carcinomas, and the altered integrin expression is suspected to be associated with cellular carcinogenesis, ${\alpha}v$ integrin subunit and ${\alpha}v{\beta}6$ integrin did not express in oral cancer cell lines tested. Cell behavior to the ECM proteins in HOK-16B line was generally similar to that of exponentially proliferating NHOKs. The adhesion activity profiles of type I collagen were very similar to that of its laminin counterparts, but fibronectin showed minimal adhesion activity under our conditions compared to the BSA control. The ability of the CTHOK-16B-BaP line to spread upon type I collagen and laminin markedly decreased, but migration was notably increased on type I collagen. In contrast, CTHOK-16B-DMBA and CTHOK-16B-Dexa lines spread less but migrated more upon type I collagen than immortalized HOK-16B line. These data indicate that downregulation of integrin subunits causes the changes of cellular responses to the ECM proteins during neoplastic conversion of human oral keratinocytes, and that cellular responses to the ECM proteins in oral cancer cell lines established by exposing different carcinogens are variable according to chemical carcinogens treatment.

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

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.10
• /
• pp.4873-4878
• /
• 2012

Apoptosis is programmed cell death which is essential for development and survival of living organisms. It is a sequentially regulated suicidal programme where cells activate certain enzymes which dissolute their own nuclear component and various protein component of nucleus and cytoplasm. Disturbance of this regulatory pathway may lead to various diseases like autoimmune diseases, neurodegenerative diseases and cancers. The potential mechanisms of apoptosis and its role in cancer are discussed. The ability of apoptosis to modulate the life or death of a cell is also recognized for its immense therapeutic potential. Understanding the mechanisms from this review will give us better insight to the pathogenesis of various diseases including cancer and will open new horizons to therapeutic approaches.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.32 no.3
• /
• pp.209-215
• /
• 2006

Preoperative neoadjuvant chemotherapy using cisplatin and 5-FU is generally given in oral and maxillofacial cancer. At tissue level both inflammation and fibrosis occur after chemotherapy. The cellular changes mimic those of a granulating wound, with activated macrophages and fibroblasts replacing the malignant cells as they are erradicated. Stromal cells, together with extracellular matrix components, provide the microenvironment that is pivotal for tumor cell growth, invasion, and metastatic progression. Vascular endothelial growth factor(VEGF), an important regulator of angiogenesis in cancer, induces mitogenesis of vascular endothelial cells, and vascular permeabilization and microvessel formation in a tumor are associated with tumor nutrition and oxygenation. Also, they are associated with chemotherapeutic drug delivery. Oxygen delivery to tumor appears to rely on a network of microvessels, On the other hand, the tumor microvessel is clearly an important factor in chemotherapeutic drug delivery to cancer cells, and the efficacy of drug delivery can be high in richly vascularized tumors. So, this study was conducted to evaluate the effect of neoadjuvant chemotherapy on microvessel density from 11 patients with tongue cancers. Our results showed that neoadjuvant chemotherapy was seemed to decrease VEGF expression in tumor cells, however, it did not significantly alter VEGF expression in tumor-associated macrophages. Also, Neoadjuvant chemotherapy had little effect on the microvessel density using CD34, and tumor-associated macrophage level using CD68. Thus, tumorassociated macrophages seem to be the key factor associated with the maintenance of microvessel density after neoadjuvant chemotherapy in tongue cancer.

• Biomedical Science Letters
• /
• v.17 no.1
• /
• pp.85-88
• /
• 2011

Tumor angiogenesis, which is essential for tumor growth and tumor metastasis, depends on angiogenic factors produced by tumor cells and/or infiltrating cells such as endothelial cells and immune cells in tumor tissue. Previously, we reported that licochalcone A (LicA), an important bioactive compound of Glycyrrhiza inflate, suppresses angiogenesis, tumor growth and metastasis. In this study, we evaluated the effect of LicA on angiogenin production in colon cancer cells because angiogenin is an essential factor to regulate angiogenesis and tumor progression. When we examined the angiogenin levels in three human colon cancer cells, HT-29, SW480 and Caco-2, LicA treatment significantly reduced the amounts of angiogenin among three cancer cell lines. In an in vivo study in which mice were implanted with HT-29 cells, oral administration of LicA reduced angiogenin in tumor tissues when compared with vehicle-administered mice. These results suggest that reduced angiogenin in response to LicA treatment may play essential role to inhibit tumor growth, angiogenesis as well as metastasis.

• Journal of Food Hygiene and Safety
• /
• v.29 no.3
• /
• pp.248-251
• /
• 2014

Dryopteris crassirhizoma is one of the naturally occurring substance wood ferns and is known for having anti-inflammatory, antiviral and anthelmintic activities. However, there is less report about its anticancer effect in human cancer cell lines. In the present study, the effect of methanol extract of dryopteris crassirhizoma (MEDC) on apoptosis in human oral cancer cell lines (MC3 and HN22 cells) was investigated. MEDC inhibited cell viability and induced apoptosis. MEDC significantly increased Bak and truncated Bid proteins in MC3 cells and elevated only truncated Bid compared to the control while other Bcl-2 family proteins were not altered. MEDC has anticancer activity by inducing apoptotic cell death through the regulation of either Bak or Bid. These findings suggest that its extract possibly may be used for treating oral cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.11
• /
• pp.5753-5757
• /
• 2012

Apoptosis, also known as cell suicide or programmed cell death, removes unwanted and genetically damaged cells from the body. Evasion of apoptosis is one of the major characteristic features of rapidly proliferating tumor cells. Chemopreventive agents inhibit or suppress tumor formation through apoptotic induction in target tissues. The aim of the present study was to investigate the pro-apoptotic potential of lupeol during 7,12-dimethylbenz(a) anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Topical application of 0.5% DMBA three times a week for 14 weeks in the buccal pouches of golden Syrian hamsters resulted in oral squamous cell carcinoma. The expression pattern of apoptotic markers was analyzed using immunohistochemistry (p53, Bcl-2, Bax) and ELISA reader (caspase 3 and 9). In the present study, 100% tumor formation with defects in apoptotic markerexpression pattern was noticed in hamsters treated with DMBA alone. Oral administration of lupeol at a dose of 50mg/kg bw completely prevented the formation oral tumors as well as decreased the expression p53 and Bcl-2, while increasing the expression of Bax and the activities of caspase 3 and 9. The present study thus indicated that lupeol might inhibit DMBA-induced oral tumor formation through its pro-apoptotic potential in golden Syrian hamsters.