• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.237-242
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• 2013

Cervical cancer is the second most common cause of cancer in women and has a high mortality rate. Cisplatin, an antitumor agent, is generally used for its treatment. However, the administration of cisplatin is associated with side effects and intrinsic resistance. Morinda citrifolia (Noni), a natural plant product, has been shown to have anti-cancer properties. In this study, we used Noni, cisplatin, and the two in combination to study their cytotoxic and apoptosis-inducing effects in cervical cancer HeLa and SiHa cell lines. We demonstrate here, that Noni/Cisplatin by themselves and their combination were able to induce apoptosis in both these cell lines. Cisplatin showed slightly higher cell killing as compared to Noni and their combination showed additive effects. The observed apoptosis appeared to be mediated particularly through the up-regulation of p53 and pro-apoptotic Bax proteins, as well as down-regulation of the anti-apoptotic Bcl-2, Bcl-$X_L$ proteins and survivin. Augmentation in the activity of caspase-9 and -3 was also observed, suggesting the involvement of the intrinsic mitochondrial pathway of apoptosis for both Noni and Cisplatin in HeLa and SiHa cell lines.

• International Journal of Oral Biology
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• 제32권3호
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• pp.93-101
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• 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.

• 생명과학회지
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• 제31권12호
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• pp.1057-1065
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• 2021

위암 환자에서 미토콘드리아 DNA (mtDNA)의 양적 변화가 보고 되고 있으며 이러한 변화가 위암의 발암이나 진행에 관여되는 것으로 추정되고 있다. 그리나 위암에서 미토콘드리아 단백질이나 mtDNA에 의해 암호화된 산화적 인산화(OXPHOS) 단백질의 양적 변화에 관한 연구는 아직까지 미비한 실정이다. 본 연구에서는 위암환자 조직 및 세포주를 이용하여 mtDNA 양 그리고 미토콘드리아 단백질 및 OXPHOS 단백질의 양을 분석하였다. 또한, mtDNA 양적 변화와 위암 환자의 임상병리학적 특징을 연관 분석하였다. MtDNA 양을 분석하기 위하여 qPCR 기법을 그리고 단백질 분석에는 Western blot 기법을 각각 활용하였다. 총 27개의 위암 환자 샘플에서 약 80%에 해당하는 22개의 환자 위암조직에서 정상조직에 비해 mtDNA 양이 감소하였으며, 나머지 환자에서는 mtDNA 양이 증가하였다. 이러한 mtDNA 양이 감소한 위암 조직 샘플에서는 미토콘드리아 단백질 및 OXPHOS 단백질의 양도 같이 감소하였다. 한편, 본 연구에 사용된 총 5개의 위암 세포주 모두에서 mtDNA 양이 감소하였다 그러나 위암 세포주에서는 mtDNA 양적 감소와 미토콘드리아 단백질 및 OXPHOS 단백질의 양적 감소가 항상 일치하지는 않았다. 이러한 연구결과는 위암 조직 및 세포주에서 mtDNA 양의 감소가 흔하며 이는 mtDNA 양적 변화가 위암의 생성에 관여함을 제시한다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7553-7558
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• 2014

The Piwi subfamily comprises two argonaute (Ago) family proteins, which are defined by the presence of PAZ and Piwi domains, with well known roles in RNA silencing. Hiwi, a human Piwi subfamily member, has been shown to play essential roles in stem cell self-renewal and gametogenesis. Recently, accumulating reports have indicated that abnormal hiwi expression is associated with poorer prognosis of multiple types of human cancers, including examples in the breast. However, little is known about details of the oncogenic role of hiwi in breast cancers. In present study, we confirmed overexpression of hiwi in breast cancer specimens and breast cancer cell lines at both mRNA and protein levels. Thus both RT-qPCR and Western blot data revealed significantly higher hiwi in intratumor than peritumor specimens, overexpression being associated with tumor size, lymph node metastasis and histological grade. Hiwi overexpression was also identified in breast cancer cell lines, MDA-MB-231 and MCF-7, and gain-of-function and loss-of-function strategies were adopted to identify the role of hiwi in the MCF-7 cell growth. Results demonstrated that hiwi expression in MCF-7 cells was significantly up- or down-regulated by the two strategies. We next evaluated the influence of hiwi overexpression or knockdown on the growth of breast cancer cells. Both cell count and colony formation assays confirmed promoting roles of hiwi in MCF-7 cells, which could be inhibited by hiwi specific blockage by siRNAs. In summary, the present study confirmed overexpression of hiwi in breast cancer specimens and breast cancer cell lines, and provided e vidence of promotion by hiwi of cell growth. The results imply an oncogenic role of hiwi in breast cancers.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제27권6호
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• pp.535-542
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• 2001

The purpose of this study was to examine the mRNA levels of TNF-${\alpha}$ and IL-6 in the cell lines of normal oral keratocyte and oral squamous cell carcinoma. Total RNA was extracted from these cell lines, observed under UV light, developed by radiographic films of PCR products via reverse transcriptase polymerase chain reaction(RT-PCR) amplication, and measured with densitometer. Each mRNA level of these cell lines divided by ${\beta}$-actin mRNA level was compared to that of normal control group. The results were as follows: 1. Higher mRNA expression of TNF-${\alpha}$ than IL-6 in the normal oral epithelial cell line. 2. In general, expression of mRNA of IL-6 appeared 3-4 times more in tumor cell lines than in control group. 3. mRNA expression of TNF-${\alpha}$ showed variable expression in tumor cell lines, unlike normal cell line. 4. There are no special connections between differentiation of oral cancer cell lines and mRNA expression of TNF-${\alpha}$ and IL-6. From the above results, expression of mRNA of IL-6 in the cell lines of squamous cell carcinoma used in this study has higher than the normal oral epithelial cell line, but there are no relationship between the differentiation of oral cancer cell lines and the expression of mRNA of TNF-${\alpha}$ and IL-6.

• 한국융합학회논문지
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• 제12권9호
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• pp.179-183
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• 2021

본 연구는 다양한 항암성분을 함유한 Celeriac Extract의 암세포 증식에 미치는 영향을 살펴보기 위하여 실시되었다. 실험에 사용한 암 세포주는 5종으로 폐암세포 A549, 전립샘암세포 DU-145, 자궁암세포 HeLa, 유방암세포 MCF-7, 간암세포 SNU-182 로 모두 인체 유래 암 세포주를 사용하였으며 Celeriac Extract 10ug/mL, 100ug/mL, 1000ug/mL 에 대한 암세포의 증식 억제는 CCK-8 방법을 이용하여 측정하였다. 암세포 증식 억제를 살펴본 결과 Celeriac Extract 1000ug/mL는 폐암세포 A549, 전립샘암세포 DU-145, 자궁암세포 HeLa, 간암세포 SNU-182에서 유의한 증식 억제를 보였으며 농도 의존성을 나타냈다. 그러나 유방암세포 MCF-7 에서는 농도 의존적인 감소만 보였다. 결론적으로, 다양한 인간유래 암 세포주를 이용한 Celeriac Extract의 세포 증식 억제기전들은 암 예방효과 및 치료제 개발의 잠재력을 제공한다고 볼 수 있다.

• Journal of Nutrition and Health
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• 제46권6호
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• pp.503-510
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• 2013

Breast cancer is the most common malignancy in women, both in the developed and developing countries. Anthocyanins are natural coloring of a multitude of foods, such as berries, grapes or cherries. Glycosides of the aglycons delphinidin represent the most abundant anthocyanins in fruits. Delphinidin has recently been reported to inhibit the growth of human tumor cell line. Also, delphinidin is a powerful antioxidant that reportedly exerts beneficial effects in patients with advanced cancer by reducing the level of reactive oxygen species and increasing glutathion peroxidase activity. This study investigates the effects of delphinidin on protein ErbB2, ErbB3 and Akt expressions associated with cell proliferation and Bcl-2, Bax protein associated with cell apoptosis in MDA-MB-231 human breast cancer cell line. MDA-MB-231 cells were cultured with various concentrations (0, 5, 10, and $20{\mu}mol/L$) of delphinidin. Delphinidin inhibited breast cancer cell growth in a dose dependent manner (p < 0.05). ErbB2 and ErbB3 expressions were markdly lower $5{\mu}mol/L$ delphinidin (p < 0.05). In addition, total Akt and phosphorylated Akt levels were decreased dose-dependently in cells treated with delphinidin (p < 0.05). Futher, Bcl-2 levels were dose-dependently decreased and Bax expression was significantly increased in cells treated with delphinidin (p < 0.05). In conclusion, I have shown that delphinidin inhibits cell growth, proliferation and induces apoptosis in MDA-MB-231 human breast cancer cell lines.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.617-622
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• 2014

Voacanga globosa (Blanco), a plant endemic to the Philippines, is traditionally used especially by indigenous people of Bataan in the treatment of ulcers, wounds and tumorous growths. This study aimed to provide scientific evidence to therapeutic properties by determining cytotoxic and pro-apoptotic activity of HPLC fractions from leaves on HCT116 human colon carcinoma and A549 human lung carcinoma cell lines. Ethanolic extraction was performed on V globosa leaves followed by hexane and ethyl acetate partitioning. Silica gel column chromatography and high performance liquid chromatography (HPLC) produced MP1, MP2 and MP3 fractions. Cytotoxic activity of the fractions was determined through MTT assay against the cancer cell lines HCT116 and A549 and the non-cancer AA8 Chinese hamster ovarian cell line. Pro-apoptotic activities of the most active fractions were further assessed through DAPI staining, TUNEL assay and JC-1 mitochondrial membrane potential assay with HCT116 cells. While the MPI fraction exerted no significant activity against all cell lines tested, MP2 and MP3 fractions demonstrated high toxicity against HCT116 and A549 cells. The MP3 fraction induced formation of apoptotic bodies, condensed DNA and other morphological changes consistent with apoptosis of HCT116 cells and TUNEL assay showed significant increase in DNA fragmentation over time. In these cells, the MP3 fraction also induced mitochondrial membrane destabilization, which is generally associated with the beginning of apoptosis. Phytochemical analysis demonstrated the presence only of saponins and terpenoids in the MP3 fraction. The results indicate that the MP3 fraction exerts cytotoxic activity on HCT116 cells via induction of apoptosis triggered by loss of mitochondrial membrane potential crucial for cell survival.

• 한국식품영양과학회지
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• 제35권6호
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• pp.671-676
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• 2006

본 연구는 생강의 대표적인 비휘발성 매운맛 성분인 [6]-gingerol이 인체 유방암세포 MDA-MB-231에서 세포사멸에 미치는 영향을 살펴보았으며 그 결과는 다음과 같다. 세포사멸을 억제하는 단백질인 Bcl-2의 발현은 [6]-gingerol의 농도가 증가할수록 발현이 감소되었으며, mRNA 수준에서도 같은 양상을 보였다. 세포사멸을 유도하는 Bax의 단백질 발현은 [6]-gingerol의 농도가 증가되어도 유의적인 차이는 나타나지 않았으며 mRNA 수준에도 별 영향을 미치지 않았다. 그러나 세포사멸의 지표로 사용되는 Bcl-2/Bax의 비율은 [6]-gingerol의 농도가 증가할수록 감소를 보였다. 그리고 [6]-gingerol의 농도가 증가할수록 caspase-3의 활성이 증가하였다. 이상의 결과들로 볼 때, 인체 유방암 세포인 MDA-MB-231에서 [6]-gingerol은 암세포의 증식을 억제하고, 세포사멸을 유도하는 효과가 있는 것으로 사료된다.

• 한방안이비인후피부과학회지
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• 제19권1호
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• pp.93-102
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• 2006

Objective : Gamisibgi-San was a drug that treated carbuncle and cellulitis. So, the purpose of this Study was to investigate effects of Gamisibgi-San on the anti-cancer and proliferation of immunocytes. Materials and Method : We used Gamisibgi-San extract(GMSGS) with freeze-dried, 8wks-old male mice and cancer cell lines(L1210, S-180) for this Study. The cytotoxicity and proliferation of cells wat tested using a colorimetric tetrazoliun assay(MIT assay). Results and Conclusion : The results of this Study were obtained as follow ; 1. GMSGS was significantly showed cytotoxicity on the L1210 cell lines and S-180 cell lines. 2. GMSGS was significantly increased in the proliferation of thymocytes and splenocytes in vitro. 3. GMSGS was significantly decreased in the proliferation of L1210 cells in L1210 cells transplanted mice. 4. GMSGS was significantly decreased in the Weight of Sarcoma in S-180 cells transplanted mice. 5. GMSGS was significantly increased in the Period of Survive in S-180 cells transplanted mice. The present author thought that GMSGS had action of anti-cancer by becoming immunocytes activity(proliferation of thymocytes and splenocytes).