• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.699-705
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• 2015

Vemurafenib has recently been used as drug for treatment of melanomas with $BRAF^{V600E}$ mutation. Unfortunately, treatment with only vemurafenib has not been sufficiently effective, with recurrence after a short period. In this study, three vemurafenib-resistant $BRAF^{V600E}$ melanoma cell lines, $A375P^R$, $A375M^R$ and SKMEL-$28^R$, were established from the original A375P, A375M and SKMEL-28 cell lines. Examination of the molecular mechanisms showed that the phosphorylation levels of MEK and ERK, which play key roles in the RAS/RAF/MEK/ERK signaling pathway, were reduced in these three cell lines, with increased phosphorylation levels of pAKTs limited to SKMEL-$28^R$ cells. Treatment of SKMEL-$28^R$ cells with 100 nM paclitaxel resulted in increased apoptosis and decreased cellular proliferation, invasion and colony formation via reduction of expression levels of EGFR and pAKTs. Moreover, vemurafenib-induced pAKTs in SKMEL-$28^R$ were decreased by treatment with an AKT inhibitor, MK-2206. Taken together, our results revealed that resistance mechanisms of $BRAF^{V600E}$-mutation melanoma cells to vemurafenib depended on the cell type. Our results suggested that paclitaxel should be considered as a drug in combination with vemurafenib to treat melanoma cells.

• 동의생리병리학회지
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• 제20권5호
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• pp.1196-1199
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• 2006

Tripterygium regelii SPRAGUE is distributed in Korea and Northern China. This extract has been used as a herb medicine, especially antiparasitic, anti-inflammatory and detoxifying agent in East asia. During our research to develop new antitumor agents from natural products, Dichlorornethane (CH$_2$Cl$_2$) extract of Tripterygium regelii SPRAGUE (DTR) showed the potent apoptotic effects in A-549 lung cancer, HeLa-3 cervical cancer, SKMEL-2 melanoma cells in a dose-dependent manner. in order to purify major compounds from DTR, column chromatography was carried out gradually. Silica gel and RP-18 column chromatography for active fractions led to the isolation of a compound. The compound determined by 1 H-NMR was turned out to De Celastrol known to have antitumor activity.

• Natural Product Sciences
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• 제8권3호
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• pp.103-107
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• 2002

Four known sesquiterpenes, laurinterol (1), isolaurinterol (2), aplysinal (3) and aplysin (4) were isolated from the Korean red alga Laurencia okamurae off Cheju Island, Korea. Their structures were identified by comparison with the literature data. Compounds 1-4 showed potent cytotoxicity against A549, SK-OV-3, SKMEL-2, XF498, and HTl5 cell lines with $EC_{50}$ values ranging from 1.2 to 17.6 ${\mu}g/ml$.

• Applied Biological Chemistry
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• 제42권1호
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• pp.68-72
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• 1999

비스 방향족 ${\alpha},{\beta}$-불포화 케톤 유도체들중 비교적 양호한 farnesyl protein transferase(FPTase) 저해활성을 나타낸 1,3-diphenylpropenone 유도체들에 대하여 in vitro에서 사람의 종양세포주인 A549(폐암)를 비롯하여 SKMEL-2(피부암), HCT-15(결장암), SKOV-3(자궁암) 및 XF-498(뇌암)등 5종의 종양 세포주에 대한 세포독성을 측정하고 기질분자의 치환기 변화에 따른 구조-활성관계(SAR)를 Free-Wilson방법과 Hansch방법으로 검토하였다. 전체적으로 styryl group중의 Y-치환기보다 benzoyl group중의 X-치환기가 세포독성에 큰 영향(X>Y)을 미쳤으며, 2,4-dichloro 치환체, 15와 2,4-dimethyl 치환체, 16이 모든 종양 세포주에 대하여 가장 높은 세포독성을 나타내었다. 또한, X-치환기는 주로 적정값$({\sigma}_{opt}=0.22{\sim}0.29})$의 약한 전자끌게$({\sigma}>0)$에 의한 전자전달 효과$({\sigma})$에 의존적으로 세포독성이 증가하는 반면에 Y-치환기는 logP, $B_1$ 및 R상수 등 다양한 요소로 영향을 미치고 있음을 알았다.

• Archives of Pharmacal Research
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• 제25권6호
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• pp.824-830
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• 2002

Four flavonoid glycosides, flavaprin (7), evodioside B (8), vitexin (11), and hesperidin (12), as well as the coumarins bergapten (1), xanthotoxin (2), and isopimpinellin (3), the lignan simplexoside (10), the steroids ${\beta}-sitosterol$ (4) and daucosterol (5), the limonoids isolimonexic acid (6) and limonin (9), and uracil (13) and myo-inositol (14) have been isolated from Euodia daniellii. The structures of these compounds were established from spectral data. Among the isolates, bergapten showed cyclooxygenase-2 inhibitory activity with an $IC_{50}$ value of $6.2{\;}{\mu\textrm{g}}/ml. Flavonoids isolated from this plant exhibited no cytotoxic activity against the human tumor cell lines, A549, SKOV-3, SKMEL-2, XF498, and HCT15.

• 대한약침학회지
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• 제14권3호
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• pp.55-61
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• 2011

Objectives: Reactive Oxygen Species(ROS) are continuously produced at a high rate as a by-product of aerobic metabolism. Since tissue damage by free radical, ROS such as hydrogen peroxide($H_2O_2$), nitric oxide(NO) increases with age. Several lines of evidence provided that ROS appears to cause to develop aging-related various diseases such as cancer, arthritis, cardiovascular disease. In this study, we have conducted to investigate the pharmacological effects of red ginseng for the development possibility to pharmacopuncture drug sources or healthy aid foods. Methods: For our aims, it was investigated the biological activities of Red Ginseng ethanol extracts (RGEE) by measuring total polyphenol contents, total flavonoid contents, DPPH radical scavenging activity, ABTS radical scavenging activity and cell viability of MCF 10A and SK-MEL-2 in vitro with MTT assay method. Results: The total polyphenol contents of RGEE was 3.06${\pm}$0.11mg/g in 10mg/ml, the total flavonoid contents of RGEE was 1.35${\pm}$0.01mg/g in same concentration. The ABTS radical scavenging activity was about 80% and that of DPPH activity was 65% in 50mg/ml of RGEE. The cell viability of SKMEL-2, skin cancer cell line was decreased and that of MCF 10A, skin normal cell line was increased. Conclusions: We conclude that RGEE may be useful as potential functional foods or pharmacopuncture drug sources on the diseases induced by oxidant stress.

• Archives of Pharmacal Research
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• 제19권4호
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• pp.321-325
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• 1996

Aiming at the development of anticancer agents by modification of phenolic benzo[c]phenanthridine alkaloid, additional hydroxyl group was put on C10 position of fagaridine (1) by a biomimetic synthetic procedure to afford 10-hydroxyfagaridine (12). All of the synthetic intermediates were also screened in vitro antitumor activities against five different cell lines as well as 12. Among them the representative cytotoxic results are shown as follows; P-quinone (11) $[ED_50;(A549=0.22; {\mu}g/ml)$, $(HCT;15=0.21 {\mu}g/ml)$, fagaridine (1) $(HCT;15=0.41 {\mu}g/ml)$, olefin (6) $(HCT; 15=0.06 {\mu}g/ml)$, acetal (7) $(SKMEL-2=0.07 {\mu}g/ml)$, dihydrofagaridne (10) $(A549=0.38 {\mu}g/ml)$, 10-hydroxyfagaridine (12) $(A 549=0.45{\mu}g/mi)$. From these observation three main remarks can be drawn; (i) the iminium part of benzo[c]phenanthridine is not essential for showing acitvities, (ii) the additional hydroxyl group did not contribute to enhance the cytotoxicity, (iii) the 3-arylisoquinolin-1(2H)-one derivatives were found to display significant in vitro antitumor activity.