Human papilloma virus in oral cancer

Soung Min Kim 대한구강악안면외과학회 2016 대한구강악안면외과학회지 Vol.42 No.6

Cervical cancer is the second most prevalent cancer among women, and it arises from cells that originate in the cervix uteri. Among several causes of cervical malignancies, infection with some types of human papilloma virus (HPV) is well known to be the greatest cervical cancer risk factor. Over 150 subtypes of HPV have been identified; more than 40 types of HPVs are typically transmitted through sexual contact and infect the anogenital region and oral cavity. The recently introduced vaccine for HPV infection is effective against certain subtypes of HPV that are associated with cervical cancer, genital warts, and some less common cancers, including oropharyngeal cancer. Two HPV vaccines, quadrivalent and bivalent types that use virus-like particles (VLPs), are currently used in the medical commercial market. While the value of HPV vaccination for oral cancer prevention is still controversial, some evidence supports the possibility that HPV vaccination may be effective in reducing the incidence of oral cancer. This paper reviews HPV-related pathogenesis in cancer, covering HPV structure and classification, trends in worldwide applications of HPV vaccines, effectiveness and complications of HPV vaccination, and the relationship of HPV with oral cancer prevalence.

Methanol extracts of Undaria pinnatifida induces apoptosis via the death-receptor and Bcl-2 family pathway in human oral cancer cells

Bo-Ram Park,Seul Ah Lee,Chun Sung Kim 조선대학교 치의학연구원 2023 Oral Biology Research (Oral Biol Res) Vol.47 No.2

Undaria pinnatifida (UP), commonly known as Wakame, is a brown algae belonging to the seaweed family. It has long been used as traditional medicine to relieve thrombosis and pain in Asian regions such as China, Japan, and Korea and has been reported to be effective in reducing body fat, acting as an antioxidant, and alleviating metabolic diseases. However, its anticancer activity against oral cancer remains unknown. Herein, we analyzed the anticancer activity and mechanism of U. pinnatifida methanol extract (MeUP) on oral cancer cell lines (FaDu, YD-38, and YD-10B). The MeUP inhibited oral cancer cells’ viability without affecting normal cells (periodontal ligament), as demonstrated by the MTT assay. Moreover, the fluorescence staining analysis revealed that UP-induced suppression of oral cancer cell proliferation was dependent on apoptosis. Furthermore, UP-induced apoptosis of oral cancer cells by inducing the hydrolysis of extrinsic apoptotic factors via death-receptors and activation of intrinsic apoptotic factors through the mitochondrial outer membrane was determined by western blot analyses. Overall, these findings suggest that the inhibitory effects of MeUP on oral cancer cells’ growth may be mediated by caspase- and mitochondrial-dependent apoptotic pathways in human oral cancer cells (FaDu, YD38, and YD-10B). Therefore, MeUP has the potential to be used as a natural chemotherapeutic drug against human oral cancer.

A Neuromedin B Receptor Blockade Inhibits the Growth of Human Oral Cancer Cells

Hyun-Joo Park,Jae-Hoon Jeon,Mi-Kyoung Kim,Mi Heon Ryu,Yong-Deok Kim,Soo-Kyung Bae,Moon-Kyoung Bae KOREAN ACADAMY OF ORAL BIOLOGY 2014 International Journal of Oral Biology Vol.39 No.1

Neuromedin B (NMB) acts as a growth factor or a morphogen and plays a role in cancer progression. Indeed, the NMB receptor (NMB-R) is overexpressed in different types of tumors. In our current study, we investigated the involvement of NMB-R in the proliferation of oral cancer cells. Human oral squamous cell carcinoma (SCC) and human oral cancer cells, SCC-25 cells were found to be NMB-R-positive. The NMB-R antagonist PD168368 inhibited the proliferation of SCC-25 cells and reduced their colony formation capacity. We also found that PD168368 induced the cell cycle arrest and apoptosis of SCC-25 cells in a dose-/time-dependent manner. Overall, this antitumor activity of PD168368 in human oral cancer cells suggests that NMB-R is a potential target for the future prevention and treatment of human cancers. Neuromedin B (NMB)는 gastrin-releasing peptide (GRP)와 함께 포유동물의 bombesin-like peptide계로 잘 알려져 있다[1]. Bombesin-like peptide는 외분비, 평활근 수축, 혈관 및 혈당 조절, 체온조절과 같은 생리적 기능 조절에 관여하는 것으로 알려져 왔다[2]. 최근에는 bombesin-like peptide와 그의 수용체가 폐암, 유방암, 위암, 대장암, 전립선암과 같은 여러 가지 고형암에서 과다발현되는 것으로 알려지면서 암에서의 bombesin-like peptide와 그 수용체의 역할에 대해 관심을 가지기 시작하였다[3,4]. 다양한 연구들에서 GRP와 NMB는 다양한 암세포의 증식 및 전이를 촉진시키고, 고형암의 성장에 필수적인 혈관 신생을 증가시키는 것으로 보고되고 있다[5,6]. 이와 같은 사실에 기반을 두고 GRP 수용체의 저해를 통하여 인간 악성종양의 치료제로써의 가능성이 제시되고 있다[7]. 여러 가지 연구에서 GRP 수용체의 길항제, 단일클론항체, 안티센스 올리고헥산염을 이용하여 인간 종양 및 실험동물의 암에 대한 억제효능이 증명되고 있다[8,9]. 반면에 NMB 수용체 길항제가 개발되었지만 항암 효능에 대한 연구는 거의 알려져 있지 않았으나 최근 본 연구실에서 NMB 수용체 길항제가 유방암 성장을 억제한다는 사실을 연구하여 보고한 바 있다[10]. 두경부 편평세포암종(head and neck squamous cell carcinoma; HNSCC)는 전세계적으로 6번째로 호발되는 암이며 이중 10%가 구강 편평세포암종(oral squamous cell carcinoma; OSCC)에 해당된다고 알려져 있다[11]. 최근 OSCC에서 세포생물학적, 분자생물학적 연구에 대한 증가로 OSCC에서의 생물학적 마커의 동정 및 분자생물학적 표적 발굴과 같은 신개념의 암 예방 및 치료제 개발에 많은 관심이 모아지고 있다[12-14]. HNSCC에서 GRP 수용체의 발현양상이 보고되고 있지만 구강암을 포함한 두경부암에서 NMB 수용체의 발현 및 기능에 대한 연구는 전무하다. 본 연구에서는 NMB 길항제가 구강 암세포주의 증식에 미치는 영향을 조사하고 그 기전을 밝힘으로써 NMB 수용체 길항제의 구강암에 대한 항암효능에 대한 가능성을 제시하고자 한다.

Apoptosis induced by water extracts of Nypa fruticans wurmb via a mitochondria-dependent pathway in human FaDu hypopharyngeal squamous carcinoma cells

Seul Ah Lee,Mi Suk Choi,Bo-Ram Park,Jin-Soo Kim,Chun Sung Kim 대한구강생물학회 2021 International Journal of Oral Biology Vol.46 No.4

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.

YD-10B 인간구강암세포주에서 생강 유기용매 분획물의 항산화, 트롬빈억제 및 thrombin에 의해 처리된 암 침윤 및 전이 억제 효과

김은정(Eun-Jung Kim),김준호(Jun-Ho Kim) 한국생명과학회 2016 생명과학회지 Vol.26 No.11

구강편평세포암종은 구강 내에서 발생하는 가장 흔한 암의 형태로서, 구강암의 90%이상을 차지한다. 구강암은 국소적인 침윤의 양상을 나타내며 또한 조기진단과 치료가 용이하여 암예방을 위한 유용한 모델로 인정되고 있다. 본 연구에서는 생강 유기용매 분획물의 항산화 활성, 트롬빈억제 및 PMA 또는 thrombin에 의해 유도된 MMP- 2 및 MMP-9활성 억제 효과를 조사하였다. 시료들은 생강 열수 추출물을 헥산(hexane), 클로로포름(chloroform), 에틸 아세테이트(Ethyl acetate), 부탄올(butanol) 및 물(H₂O)과 같은 용매로 분획화하여 사용하였고, H2O 분획물의 수득율이 9.79%로 가장 높았다. 항산화 활성은 DPPH assay, 세포 생존율 측정은 MTS assay, 항염증 활성은 마우스 대식세포 Raw 264.7세포에서 NO 생성 그리고 MMP-2 및 MMP-9의 mRNA 발현 및 단백질 활성 억제는 인간구강편평세포암종 YD-10B 세포에서 RT-PCR과 zymography방법을 통해 측정하였다. 본 연구의 결과에 의하면 MMP-2/-9 활성은 PMA에 의해 YD-10B세포에서 증가하였고, thrombin 처리에 의해서는 MMP-9 활성이 유의한 증가를 보였다. YD-10B 세포에서, PMA 또는 thrombin처리 모두에서 hexane 분획물이 MMP-2/-9의 mRNA 발현 및 단백질 활성을 유의하게 억제하였다. 그리고 항산화 활성은 hexane과 H₂O 분획물에서 92.38%와 92.96%로 높게 나타났다. 또한 H2O 분획물에서 65.86%로 가장 유의하게 트롬빈 억제 활성을 보였다. 그러므로 본 연구에서는 생강 hexane분획물이 구강암의 우수한 암 침윤 및 전이 억제제로서의 개발 가능성을 제시하고 있다. Oral squamous cell carcinoma (OSCC) is a common malignant tumor in the oral cavity, comprising up to 90% of oral cancer. Oral cancer is characterized by a marked tendency of local invasiveness and is good for early detection and treatment; therefore, it is recognized as a good model for cancer prevention. The present study investigated the antioxidant, thrombin inhibitory, and anti-invasive activities of the solvent fractions of Zingiber officinale Roscoe. Samples were fractionated into hexane, chloroform, ethyl acetate, butanol, and water fractions, and each of these was assayed individually. The water fraction showed the highest extraction yield at 9.79%(w/w). Anti-oxidative activity was analyzed by DPPH assay. Thrombin inhibitory activity was used to analyze thrombin inhibitor assay. Cell viability was detected by the MTS assay. The activity and mRNA expression of MMP-2 and MMP-9 in human oral squamous carcinoma YD-10B cells were examined by zymography and RTPCR. The antioxidative activities of hexane and water fractions were 92.38% and 92.96%, respectively. In the thrombin inhibitory activity test, water fraction was the highest, with a value of 65.86%. MMP-2/-9 activation was increased in phorbol 12-myristate 13-acetate (PMA)-induced YD-10B cells. MMP-9 activation was increased in thrombin-treated YD-10B cells. In PMA- or thrombin-treated YD-10B cells, the increased mRNA expression and protein activation of MMP-2/-9 were significantly inhibited in the hexane fraction. Therefore, the hexane fraction obtained from a Zingiber officinale Roscoe water extract is a promising therapeutic anti-invasive agent in oral cancer.

Saliva-Based Screening of High-Risk Human Papillomavirus Strains: Detection in Female Indonesian and Thai Dental Students

Wimardhani, Yuniardini Septorini,Sasanti, Harum,Wardhany, Indriasti Indah,Sarsito, Afi Savitri,Pradono, Siti Aliyah,Subita, Gus Permana,Soegyanto, Anandina Irmagita,Rahmayanti, Febrina,Chamusri, Nutch Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.13

Background: Currently it is believed that human papillomaviruses (HPV) are associated with the development of some oral/oropharyngeal cancers. It has been suggested that these viruses influence carcinogenesis in both smokers and non-smokers. Data on the prevalence of HPV in healthy adults are thus needed to estimate the risk of oral/oropharyngeal cancer. The aim of this study was to assess the prevalence of oral HPV in healthy female adults in Indonesia and Thailand. Materials and Methods: Healthy female students from the Faculties of Dentistry of Universitas Indonesia and Chiang Mai University were asked to participate in this pilot study. DNA was extracted from saliva specimens and screened for HPV16 and HPV18 using PCR. Results: The age, marital status and sexual experience of the subjects between the two countries were not significantly different. Eight (4%) and 4 (2%) samples were positive for HPV16 and HPV18, respectively. Fisher's Exact test found a significant difference between HPV16 positivity in subjects who were married and had sexual intercourse but not for HPV18. Conclusions: This study successfully detected presence of HPV16 and HPV18 DNA in a number of saliva samples from female dental school students. Marital status, experience of sexual intercourse and safe sexual practice are related to the possibility of finding HPV DNA finding in saliva. Dentists, physicians and other health care professionals may gain significant value from the findings of this study, which provide an understanding of the nature of HPV infection and its risk to patient health and disease.

Methanol extracts of Asarum sieboldii Miq. inducesapoptosis via the caspase pathway in human FaDuhypopharynx squamous carcinoma cells

Seul Ah Lee,Bo-Ram Park,Chun Sung Kim 대한구강생물학회 2021 International Journal of Oral Biology Vol.46 No.2

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.

Lycorine induces apoptosis by enhancing protein degradation of survivin in human oral cancer cell lines

정요셉,조남표,장분실 대한구강악안면병리학회 2017 대한구강악안면병리학회지 Vol.41 No.1

Lycorine, a natural alkaloid extracted from the Amaryllidaceae plant family, was reported to various physiological and pharmacological effects including anti-cancer activity. Nevertheless, there is no report of the anticancer effect of lycorine in oral cancer cells. The effects of lycorine on cell proliferation and apoptosis were examined through trypan blue exclusion assay, 4’-6-diamidino-2-phenylindole (DAPI) stain, Live/Dead assay, Western blot analysis and RT-PCR. Lycorine suppressed cell viability and induced apoptosis in MC3 and HSC-3 cell lines. Lycorine decreased survivin protein but did not affect its mRNA. It regulated survivin through accelerating protein degradation in a time-dependent manner although neither proteasome nor lysosome was not associated with lycorine-mediated protein degradation. Collectively, our results suggest that lycorine may be a potential therapeutic anti-cancer drug candidate for the treatment of human oral cancer.

Lycorine의 사람 구강 암 세포주에서 survivin 단백질 분해 증진으로 세포자멸사

Joseph H. Jeong,Nam-Pyo Cho,Boonsil Jang 대한구강악안면병리학회 2017 대한구강악안면병리학회지 Vol.41 No.1

Lycorine, a natural alkaloid extracted from the Amaryllidaceae plant family, was reported to various physiological and pharmacological effects including anti-cancer activity. Nevertheless, there is no report of the anticancer effect of lycorine in oral cancer cells. The effects of lycorine on cell proliferation and apoptosis were examined through trypan blue exclusion assay, 4’-6-diamidino-2-phenylindole (DAPI) stain, Live/Dead assay, Western blot analysis and RT-PCR. Lycorine suppressed cell viability and induced apoptosis in MC3 and HSC-3 cell lines. Lycorine decreased survivin protein but did not affect its mRNA. It regulated survivin through accelerating protein degradation in a time-dependent manner although neither proteasome nor lysosome was not associated with lycorine-mediated protein degradation. Collectively, our results suggest that lycorine may be a potential therapeutic anti-cancer drug candidate for the treatment of human oral cancer.

Microarray analysis in KB human oral cancer cells treated with neuron restrictive silencer factor siRNA

( Woo Jin Jun ),( Eugene Cho ),( Myung Mi Kim ),( Mi Suk Choi ),( Joong Ki Kook ),( Su Gwan Kim ),( Do Kyung Kim ),( Heung Joong Kim ),( Young Ju Cha ),( Sung Kyu Lee ),( Chun Sung Kim ) 조선대학교 구강생물학연구소 2012 Oral Biology Research (Oral Biol Res) Vol.36 No.1

Strong expression of neuron restrictive silencer factor (NRSF) has been observed in many aggressive types of cancer cells and mature neurons. However, the function of the neuron restrictive silencer element (NRSE)/NRSF system in KB human oral cancer cells is unknown. Findings from previous studies in our lab have demonstrated the importance of NRSF as a factor in regulationof cell proliferation of KB human oral cancer cells. Treatment of KB cells with NRSF siRNA resulted in signifi cant inhibitionof cell growth through repression of NRSF expression. In this study, in order to understand the NRSE/NRSF regulatory network in KB cells, we performed microarray analysis in KB cells treated with NRSF specifi c targeted siRNA. The expression profi les of several genes were further validated in KB cells treated with NRSF siRNA. Results of microarray analysis showed upregulation of 117 genes and down-regulation of 215 genes in KB cells treated with NRSF siRNA. Most of the up-regulated genes were involved in signal transduction, cell communication, cell cycle, and apoptosis;down-regulated genes were involved in RNA processing, neurogenesis, transcription factor activity, and synaptogenesis. NRSF is known as a transcriptional repressor for silencingof neuronal genes; however, according to our data, treatment of KB cells with NRSF siRNAresulted in down-regulation of more than 200 genes. As a result, genes identifi ed in this screen represent a novel control pathway via NRSF expression in KB oral cancer cells. Further investigation will be needed in order to defi ne the mechanism of gene regulation by expression of NRSF in KB human oral cancer cells.