• 한국식품영양과학회지
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• 제40권1호
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• pp.37-46
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• 2011

22종의 고구마에 대한 총 페놀함량 및 항돌연변이원성을 평가하였다. 17종의 비자색고구마 중 수, 하얀미, 신황미 품종의 총 페놀함량이 21.4, 21.5, $20.3{\mu}g$(GEA/g dried sweet potato)으로 가장 높았으며, 맛나미와 연황미 품종에서 4.6과 $4.8{\mu}g$으로 가장 낮았다. 5종의 자색고구마에서 총 페놀함량은 자미 품종이 $128.3{\mu}g$으로 가장 높았으나, 신자미 품종에서 $44.9{\mu}g$으로 가장 낮았다. 1-NP, daunomycin, Trp-P-1, Trp-P-2, 2-AA에 의해 돌연변이가 유도된 S. Typhimurium TA 98과 1-NP에 의해 돌연변이가 유도된 S. Typhimurium TA 100에 있어서 돌연변이 억제효과는 고구마 메탄올 추출물은 대체적으로 효과적이었으며, 자색고구마에 있어서는 자미와 아야무라사키 품종에서 높았다. 총 페놀함량이 많은 자색고구마는 2-AA에 대해서만 높은 돌연변이 억제효과를 나타내었을 뿐 1-NP, daunomycin, Trp-P-1, Trp-P-2에 대해서는 비자색고구마와 뚜렷한 차이를 보이지 않았다. 자색고구마 품종 간에 있어서는 총 페놀함량이 많을수록 돌연변이 억제효과가 높았다. 고구마의 품종별 항돌연변이 효과는 총 페놀 함량보다는 사용된 돌연변이원 및 균주에 따라 좌우되는 경향이었다.

• Archives of Pharmacal Research
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• 제28권7호
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• pp.823-828
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• 2005

Multidrug resistance (MDR) is one of the most significant obstacles in cancer chemotherapy. One of the mechanisms involved in the development of MDR is the over-expression of P-glycoprotein (P-gp). It is widely known that natural compounds found in vegetables, fruits, plant-derived beverages and herbal dietary supplements not only have anticancer properties, but may also modulate P-gp activity. Therefore, the purpose of this investigation was to examine the effects of naturally occurring products on P-gp function in human breast cancer cell lines, MCF-7 (sensitive) and MCF-7/ADR (resistant). The accumulation of daunomycin (DNM), a P-gp substrate, was greater in the sensitive cells compared to the resistant cells, while the efflux of DNM was higher in the resistant cells compared to the sensitive cells over a period of 2h. The $IC_{50}$ value of DNM in the resistant cells was about 22 times higher than that in the sensitive cells, indicating an over-expression of P-gp in the resistant cells, MCF-7/ADR. All of the compounds tested, with the exception of fisetin, significantly decreased the $IC_{50}$ value of DNM. Biochanin A showed the greatest increase in $[^3H]-DNM$ accumulation, increasing by $454.3{\pm}19.5%$ in the resistant cells, whereas verapamil, the positive control, increased the accumulation by $229.4{\pm}17.6%$. Also, the accumulation of $[^3H]-DNM$ was increased substantially by quercetin and silymarin while it was reduced by fisetin. Moreover, biochanin A, silymarin, and naringenin significantly decreased DNM efflux from MCF-7/ADR cells compared with the control. These results suggest that some flavonoids such as biochanin A and silymarin may reverse MDR by inhibiting the P-gp function.

• Bulletin of the Korean Chemical Society
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• 제31권1호
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• pp.69-74
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• 2010

The new idarubicin analogues (12 and 13) with a glucose or galactoseas as a glycone were synthesized from daunomycin (2). (+)-4-Demethoxydaunomycinone (6) obtained from reaction of 2 with $AlCl_3$ was converted to 4-trifluoromethanesulfonyl daunomycinone (7) through reaction with trifluoromethanesulfonic anhydride. The treatment of 7 with 1,1-bis-(diphenylphospino)ferrocene/$Pd(OAc)_2$ in triethylamine/formic acid/dioxane provided the idarubicinone (5b). Glycosylation of 7-hydroxy group of 5b with two kinds of tetraacetyl pyranosyl halide (8 and 9) by a modified Koenigs-Knorr procedure and then deacetylation using aqueous 0.1 N LiOH solution and amberlite cationic resin gave the objective materials. The in vitro MTT assay of the analogues (12b and 13a) in comparison with idarubicin (5a) on peripheral blood human promyelocytic-leukemia cell line and human breast cancer cell line were also described.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.231.2-231.2
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• 2003

One of the possible mechanisms of multi-drug resistance found in cancer cells is the over-expression of P-glycoprotein (P-gp). Studies have shown that compounds found in plants including vegetables and fruits not only have anticancer activities but may also modulate P-gp activity. The effect of flavonoids and organic isothiocyanates on P-gp activity was studied in human uterine sarcoma cell lines, MES-Sa (sensitive) and MES-SD/DX5 (resistant). The accumulation of daunomycin (DNM), a P-gp substrate, was approximately 10 times greater in the sensitive cell as compared to the resistant cells over the entire time course (up to 2 hrs). (omitted)

• Natural Product Sciences
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• 제10권2호
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• pp.85-88
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• 2004

One hundred Indonesian plant extracts were screened to investigate their effects on the P-glycoprotein (P-gp) activity in human uterine sarcoma cells, MES-SA/DX5, for the first time. Among others, four samples, Alpinia galanga (BuOH ext.), Sindora sumatrana $(CHCl_3\;ext.)$, Strychnos ligustrina $(CHCl_3\;ext.)$, and Zingiber cassumunar Roxb (hexane ext.), exhibited the most potent inhibition on the P-gp activity. They increased cytotoxic activity of daunomycin up to $IC_{50}$ values of less than $1.41\;{\mu}M$, which is a value with a positive control, verapamil. Other 25 samples showed significant P-gp inhibitory activity with $IC_{50}$ values between 1.4 and $4.0\;{\mu}M$. These prospective samples will be subjected to further laboratory phytochemical investigation to find active principles.

• Journal of Pharmaceutical Investigation
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• 제33권4호
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• pp.305-310
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• 2003

One of the possible mechanisms of multi-drug resistance found in cancer cells is the over-expression of P­glycoprotein (P-gp). Studies have shown that compounds in plants including vegetables and fruits not only have anticancer activities but may also modulate P-gp activity. The effect of flavonoids and organic isothiocyanate on P-gp activity was studied in human uterine sarcoma cell lines, MES-SA (sensitive) and MES-SA/DX5 (resistant) cells. The accumulation of daunomycin (DNM), a P-gp substrate, was approximately 10 times greater in the sensitive cell as compared to the resistant cells over the entire time course (up to 2 hours). The positive control, verapamil increased the two hour accumulation of DNM while quercetin decreased that of DNM in the resistant cells. 1-Naphtyl-isothiocyanate (NITC) showed no effect on the two hour accumulation of DNM. The $IC_{50}$ values for DNM in the resistant cells was about 20 times higher than that observed in the sensitive cells $(10.1{\pm}1.7\;{\mu}M\;vs.\;0.58{\pm}0.28\;{\mu}M)$. Verapamil reduced the $IC_{50}$ value for DNM whereas flavonoids (quercetin and fisetin) increased those for DNM in the resistant cells.

• Biomolecules & Therapeutics
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• 제25권5호
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• pp.553-558
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• 2017

Paclitaxel (PTX) is one of the most frequently used anticancer agent for treating refractory ovarian cancer, metastatic breast cancer and non-small cell lung cancer. However, its oral administration is impeded by very low bioavailability (<5%) due to the P-glycopprotein (P-gp) efflux pump effect. This study investigated in vitro and in vivo P-gp inhibitory effects of adamantyl derivatives AC-603 and AC-786 in rats. Two adamantyl derivatives tested in this study increased the cytotoxicity of daunomycin (DNM) in P-gp overexpressed cell line by inhibiting P-gp efflux function. Pharmacokinetics of PTX with orally co-administered P-gp inhibitors were assessed in rats to improve PTX absorption. The pharmacokinetic parameters of PTX were determined in rats after intravenous (2 mg/kg) or oral (25 mg/kg) administration in the presence or absence of verapamil (a positive control), AC-603 or AC-786 (0.5 mg/kg or 5 mg/kg). Compared to control group (PTX alone), experimental groups (PTX with AC-603 or AC-786) significantly increased the area under the plasma concentration-time curve of PTX following oral administration by 1.7-2.2 fold. The volume of distribution and total clearance of PTX were decreased, while other parameters were not significantly changed. In conclusion, co-administration of AC-603 or AC-786 enhanced the relative bioavailability of orally administered PTX as compared to control.

• Toxicological Research
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• 제8권2호
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• pp.171-177
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• 1992

To investigate a short term screening method for carcinogenic quinone compounds, 8-hydroxydeoxyguanosine (8-OHdG), an oxidative DNA damage, was determined in the kidney and liver DNA isolated from Sprague-Dawley rats after i.p.injection of 7 mg/kg adriamycin (AM), 7mg/kg tetrahydropyranyladriamycin (THP), and 10mg/kg daunomycin (DM) by HPLC-electrochemical detector system. 8-OHdG was also determined from rat hepatocvtes and calf thymus DNA exposed to AM, DM and THP. When rats were treated with DM and THP, 8-OHdG was significantly increased in the kidney compared to control group, and remained at high level (7.9~9.0, 8-OHdG/dG${\times}10^4$)at the end of experiments (48hr after treatment). 8-OHdG level in cultured hepatocyte exposed to AM, DM and THP was 1.5~2 fold higher than control at all time points. (1,2,3,4hr after treatment). From calf thymus DNA exposed to AM, DM and THP, 8-OHdG was 2.5 fold higher than of control. These results suggest that quantitation of 8-OHdG may provide a useful marker for identifying target organ in oxidative chemical carcinogenesis and for short term screening of free radical generating carcinogens.

• 생명과학회지
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• 제24권6호
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• pp.700-706
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• 2014

본 연구에서는 anthracycline 계열 항암항생제인 doxorubicin의 암세포 전이 억제 여부를 LNCap 전립선 암세포를 이용하여 이동성 및 침윤성 억제 효능 측면에서 조사하였다. 본 연구의 결과에 의하면 doxorubicin은 LNCap 세포의 이동성과 침윤성을 현저하게 억제시켰으며, matrix metalloproteinase (MMP)-2 및 -9의 발현과 활성을 저해함과 동시에 tissue inhibitor of metalloproteinase (TIMP)-1 및 -2의 발현은 증가시켰다. Doxorubicin은 또한 tight junctions (TJs)의 전기적 저항성을 증대시켰으며, 이는 TJs의 주요 구성인자인 claudin family 인자들의 발현 억제와 연관성이 있었다. 따라서 LNCap 세포에서 doxorubicin에 의한 전이의 억제에는 최소한 TJ의 견고성 증대와 MMPs의 활성 억제가 관여할 것으로 추정된다.