• Maxillofacial Plastic and Reconstructive Surgery
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• 제28권2호
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• pp.95-110
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• 2006

The treatment for oral and maxillofacial carcinoma with chemotherapeutic agents is evaluated by many effective methods to reduce the tumor mass and cancer cell proliferation. However these chemotherapy have many serious side effects, such as bone marrow suppression, renal toxicity, G-I troubles. Therefore a possible approach to develop a clinically applicable chemotherapeutic agent is to screen anticancer activity of Taxol which is known to have very little side effect and have been used to breast cancer and ovarian carcinoma. Taxol is a new anti-microtubular anti-cancer agent extracted from the bark of the Pacific yew, Taxus brevifolia. Paclitaxel(Taxol) acts by promoting tubulin polymerization and over stabilizing microtubules agianst depolymerization. Despite the constant improvements of methods of the cancer treatment especially chemotherapy, the rate of cancer metastasis and recurrent are not decreased. Thus the investigation of new drug which have very little side effect and a possible clinically application continues to be a high priority. Considering that the Taxol have shown very effective chemotherapeutic agent with relatively low toxicity in many solid tumors, it deserves to evaluate its efficacy in oral squamous cell carcinoma. In this study, to investigate the in-vivo and in-vitro anti-cancer efficacy of Taxol in oral squamous cell carcinoma and lastly, the potency of Paclitaxel in the clinical application for oral cancer was evaluated. In vivo study, after HN22 cell line were xenografted in nude mice, the growth of tumor mass was observed, 3 mg/Kg taxol was injected intraperitoneally into nude mice containing tumor mass. The methods of these study were measurement of total volume of tumor mass, histopathologic study, immunohistochemical study, drug resistance assay, growth curve, MTT assay, flow cytometry, cDNA microarray in vivo and in vitro. The results were obtained as following. 1. The visual inspection of the experimental group showed that the volume of the tumor mass was slightly decreased but no significant difference with control group. 2. Ki-67 index was decreased at weeks 4 in experimental group. 3. Microscopic view of the xenografted tumor mass showed well differentiated squamous cell carcinoma and after Taxol injection, some necrotic tissue was seen weeks 4. 4. The growth curve of the tumor cells were decreased after 1day Taxol treatment. 5. According to the MTT assay, HN22 cell line showed relative drug resistancy above $5\;{\mu}g/ml$ concentrations of Taxol. 6. In drug resistance assay, the decrease of cell counts was seen relatively according to concentration. 7. In Flow cytometry, G2M phase cell arrests were seen in low concentration of the Taxol, while S phase cell arrests were seen in high concentration of the Taxol. 8. Using cDNA microarray technique, variable gene expression of ANGPTL4, TXNRD1, FAS, RRAGA, CTGF, CYCLINEA, P19, DUSP5, CEBPG, BTG1 were detacted in the oral squamous cell carcinoma cell after taxol treatment. In this study paclitaxel is effective against oral squamous cell carcinoma cell lines in vitro, but week effect was observed in vivo. So we need continuous study about anticancer effect of taxol in vivo in oral squamous cell carcinoma.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제29권6호
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• pp.365-373
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• 2003

Tamoxifen is an selective estrogen receptor antagonist widely used in the management of patients with breast cancer for more than 30 years. It was thought to act primarily through occupying the estrogen receptor sites in ER positive breast cancer cells and directly on cancer cell proper. These inhibitory effects, which have been shown to be independent of the ER, highlight new mechanism of therapeutic action of tamoxifen. The purposes of this study were to identify ER in oral carcinoma cell lines and to evaluate ER independent cytotoxic effect of tamoxifen. KB(SCC), HSC-3(SCC) and A253(ACC) cell line were used and capacity of cell proliferation, apoptosis, in vitro invasion and gelatin zymography were tested. ER expression of each cell line were detected by RT-PCR and immunocytochemistry. Dose dependent inhibition of cell proliferation and inhibition of gelatinolytic activity were observed in all oral carcinoma cell lines and significant difference of apoptotic index were observed in A253 and KB. Tamoxifen inhibited in vitro invasion in all experimental groups. ER expression was detected in KB and A253. These data suggest that tamoxifen may play a role in management of oral carcinoma by independent cytotoxic effect and more advanced research must processed confirming ER-dependent cytotoxicity.

• 한국약용작물학회지
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• 제13권4호
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• pp.154-160
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• 2005

자연산 인진호와 조직 배양체의 유용 생리활성을 살펴 보았다. 우선, 항암 효과를 살펴보기 위하여 인간 폐암세포(A549)와 위암세포(AGS), 인간 간암세포(Hep3B)와 유방암 세포(MCF7) 4가지 암세포주를 이용하여 세포 생육 저해능을 측정하였다. MTT assay의 경우 1.0g/l 의 농도에서 캘러스가 A549와 ACS에 대해 각각 약 45%와 42%로 모상근과 기내배양에 비해 높은 세포 생육 저해능을 나타내었고, 자연산 인진호는 약 45%와 38%로 캘러스와 비슷한 항암 활성을 나타내었다. SRB assay의 경우도 캘러스가 가장 높은 항암 효과를 나타내었는데 대체적으로 약 55% 이상의 암세포 저해율을 나타내었으며, 자연산 인진호의 항암 활성에 비해서도 높은 수치를 나타내었다. 면역세포를 이용한 생육도와 cytokine의 분비량을 측정한 결과 B 세포의 생육도는 6일째까지 계속적인 증가를 가져왔고, 이에 따라 cytokine의 분비량 또한 $TNF-{\alpha}$와 IL-6 모두 6일째까지 증가하는 경향을 나타내었다. 면역세포의 생육도의 경우는 자연산 인진호가 가장 높은 생육도를 나타내었고, 인진호의 기내배양, 모상근, 캘러스 중에서는 모상근에서 가장 높은 생육도를 나타내었다. Ctyokine의 경우도 $TNF-{\alpha}$에서 자연산 인진호의 분비량이 가장 많았고, 배양 방법에 따른 인진호의 경우 캘러스가 가장 많은 분비량을 나타내었다. IL-6의 경우는 모든 sample에서 control에 비해 높은 분비량을 나타내었고, 자연산 인진호와 기내배양, 모상근, 캘러스와 비교했을 때 큰 차이를 나타내지 않았다. HPLC 분석을 통한 추출물의 물질 비교 분석 결과 기내배양과 모상근에서는 자연산 인진호에 비해 주요 성분 peak인 artemisidin 면적이 모두 낮은 경향을 나타내었고, 캘러스의 경우는 일반 인진호에 비해 peak의 면적이 비슷한 경향을 나타법으로서, 캘러스가 다른 조직 배양체보다 인진호의 주요 성분인 artemisidin 성분의 함량이 더 높은 것으로 나타나 캘러스가 기내배양이나 모상근 보다 높은 항암 효과를 나타낸 것으로 사료되어진다. 이와 같이 자연산 인진호와 조직 배양체의 항암 효과나 면역활성에서 큰 차이를 나타내지 않았기 때문에, 이러한 조직배양체가 자연산 인진호를 대체 할 수 있는 하나의 방법으로서 환경적인 측면과 자원 보존적인 측면에서 볼 때 가치있는 결과라고 사료된다.

• 한국식품영양과학회지
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• 제41권1호
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• pp.26-32
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• 2012

국내산 정제염, 천일염과 유럽산 천일염 등의 SEM에서의 형태, 무기질 성분, 보돌연변이와 암세포 in vitro 항암 기능성을 측정하였다. 정제염은 SEM을 이용한 관찰 시 구조가 규칙적이었고 천일염은 불규칙한 표면 구조를 가지고 있었다. 천일염의 크기도 차이가 있었고 프랑스 천일염과 한국천일염I은 다른 천일염보다 크기가 작았다. 무기질 함량은 프랑스 천일염과 한국 천일염I이 Ca, K, Mg 등의 함량이 다른 소금보다 더 많았다. pH도 프랑스 천일염과 한국 천일염I이 가장 높았다. 한국산 두 가지의 천일염은 무기질 함량에 따라 물리적 특성의 차이를 보였고 한국 천일염I은 프랑스 천일염과 비슷한 무기질 함량을 가지고 있었다. 소금은 보돌연변이 효과가 있었지만 특히 무기질 함량이 높았던 프랑스 천일염과 한국산 천일염I은 다른 소금보다 낮은 보돌연변이 효과를 나타내었다. HCT-116과 AGS 암세포에 대한 in vitro 항암 효과에서도 보돌연변이 효과와 비슷한 경향을 나타내었고 많은 무기질을 함유한 프랑스 천일염과 한국산 천일염I의 암세포 성장 억제효과와 암세포의 apoptosis 유도 효과가 가장 높았다. 이상의 결과로부터 소금의 기능성은 무기질 함량이 많은 천일염이 정제염보다 좋으며 천일염 중에도 Ca, K 등의 무기질 함량이 높을수록 기능성도 증가하는 것으로 나타났다.

• 한국식품영양과학회지
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• 제38권8호
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• pp.996-1002
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• 2009

배추김치 제조 시 소금 종류별 품질 차이 및 항암 기능성 증진 효과를 알아보기 위해 정제염, 일반 천일염, 제간수 천일염, 구운소금을 사용하여 비교 연구하였다. pH 변화 및 산도에서 발효가 진행됨에 따라 정제염과 구운소금으로 제조한 김치가 일반 천일염과 제간수 천일염으로 제조한 김치에 비해 발효 속도가 지연되는 경향을 보였다. 젖산균의 변화에서는 제간수 천일염과 구운소금으로 제조한 김치에서 김치의 맛과 향을 증진시킬 수 있는 Leuconostoc sp.의 성장이 촉진되고 Lactobacillus sp.의 성장은 억제됨을 관찰할 수 있었다. 또한 제간수 천일염과 구운소금으로 제조한 김치에서 텍스쳐가 좋았고 관능검사에서도 높은 점수를 나타내었다(p<0.05). AGS 인체 위암세포와 HT-29 인체 결장암세포를 이용한 항암 효과 실험에서도 제간수 천일염과 구운소금으로 제조한 김치의 항암 기능성이 증가되었다. 따라서 총 4가지 종류의 소금 중 제간수 천일염과 구운소금으로 제조한 김치가 우수한 품질을 나타내었고 항암 기능성도 증진시켜 김치 발효에 적합한 것으로 확인되었다. 그러나 품질 및 건강 기능면과 경제적인 면을 고려해 본다면 전통적으로 사용되었던 제간수 천일염이 김치 제조 시 가장 적합한 소금으로 생각된다.

• KSBB Journal
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• 제24권6호
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• pp.570-578
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• 2009

헤마토코커스로부터 아스타잔틴의 추출과 제형화의 유효성을 확인하고 적용성을 검토하고자 헤마토코커스 추출물과 아스타잔틴 포접화합물의 생리활성을 측정하였다. 그 결과, 헤마토코커스 추출물은 DPPH 라디칼 소거능, xanthine oxidase 저해 활성 및 hydroxyl 라디칼 소거능에 대해 in vitro 실험에서 활성을 나타냈다. 또한 헤마토코커스 추출물은 대조군인 kojic acid에 비해 동일한 농도에서 2배 이상의 미백활성을 나타냈고, 자궁암 세포주 (HeLa)에 대해 대조항암물질인 5-fluorouracil (5-FU)과 비슷한 항암활성을 나타냈다. 아스타잔틴은 또한 숙취해소 효과를 갖고 있는 것으로 확인되었는데, 대조군인 지구자 추출물에 비해 1.5배 높음을 알 수 있었다. 또한, 아스타잔틴과 싸이클로덱스트린의 포접화합물 As-$\beta$-CD와 헤마토코커스 추출물과 싸이클로 덱스트린의 포접화합물인 H.p.-$\beta$-CD의 생리활성을 조사한 결과, As-$\beta$-CD는 대조군인 지구자추출물보다 높은 숙취해소 효과를 나타냈고, H.p.-$\beta$-CD는 대조군인 kojic acid와 비슷한 수준의 미백효과를 나타냈다.

• 대한약침학회지
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• 제19권3호
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• pp.213-224
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• 2016

Objectives: Ginseng Rh2+ is enzyme-treated ginseng extract containing high amounts of converted ginsenosides, such as compound k, Rh2, Rg3, which have potent anticancer activity. We conducted general and genetic toxicity tests to evaluate the safety of ginseng Rh2+. Methods: An acute oral toxicity test was performed at a high-level dose of 4,000 mg/kg/day in Sprague-Dawley (SD) rats. A 14-day range-finding study was also conducted to set dose levels for the 90-day study. A subchronic 90-day toxicity study was performed at dose levels of 1,000 and 2,000 mg/kg/day to investigate the no-observed-adverse-effect level (NOAEL) of ginseng Rh2+ and target organs. To identify the mutagenic potential of ginseng Rh2+, we conducted a bacterial reverse mutation test (Ames test) using amino-acid-requiring strains of Salmonella typhimurium and Escherichia coli (E. coli), a chromosome aberration test with Chinese hamster lung (CHL) cells, and an in vivo micronucleus test using ICR mice bone marrow as recommended by the Korean Ministry of Food and Drug Safety. Results: According to the results of the acute oral toxicity study, the approximate lethal dose (ALD) of ginseng Rh2+ was estimated to be higher than 4,000 mg/kg. For the 90-day study, no toxicological effect of ginseng Rh2+ was observed in body-weight changes, food consumption, clinical signs, organ weights, histopathology, ophthalmology, and clinical pathology. The NOAEL of ginseng Rh2+ was established to be 2,000 mg/kg/day, and no target organ was found in this test. In addition, no evidence of mutagenicity was found either on the in vitro genotoxicity tests, including the Ames test and the chromosome aberration test, or on the in vivo in mice bone marrow micronucleus test. Conclusion: On the basis of our findings, ginseng Rh2+ is a non-toxic material with no genotoxicity. We expect that ginseng Rh2+ may be used as a novel adjuvant anticancer agent that is safe for long-term administration.

• Journal of Ginseng Research
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• 제25권2호
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• pp.74-81
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• 2001

The effect of Korean Ginseng saponins (total saponin, PD saponin and PT saponin) on the serotonin type 3 receptor, which is known to be involved in nausea and vomiting following anticancer chemotherapy or the general anesthesia, was investigated. after in vitro transcribed recombinant serotonin type 3 receptor in the Xenopus laevis oocyte, classic two electrodes voltage clamp technique was used. All of ginseng saponins inhibited the response of the agonist, serotonin, on the serotonin type 3 receptor in a dose-dependent manner. PT saponin showed to have the inhibitory effect more than 2 times as potent as PD saponin. Total saponin shifted the serotonin dose response plot to the right (EC$\_$50/, 0.70$\pm$0.17 $\mu$M into 3.57$\pm$1.42 $\mu$M, and Hill coefficient, 2.14$\pm$0.60 into 1.52$\pm$1.00). Ginseng saponin did not change the reversal potential (∼0 mV) of serotonin type 3 receptor. These results suggest that Korean ginseng saponin may have the inhibitory effect on serotonin type 3 receptor.

• International Journal of Oral Biology
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• 제47권3호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1655-1659
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• 2016

Celecoxib, a selective inhibitor of COX-2, showed cytotoxic effects in many cancer cell lines including cervical cancer cells. This study investigated the effect of celecoxib on cell cycle arrest in HeLa cervical cancer cells through p53 expression. In vitro anticancer activity was determined with the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) method. A double staining method was applied to investigate the mechanism of cell death, cell cycling was analyzed by flow cytometryand immunocytochemistry was employed to stain p53 expression in cells. Celecoxib showed strong cytotoxic effects and induced apoptosis with an $IC_{50}$ value of $40{\mu}M$. It induced cell cycle arrest at G2/M phase by increasing level of p53 expression on HeLa cells.