• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.1
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• pp.37-46
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• 2011

Polyphenolic content and antimutagenicity of the methanol extracts prepared from 22 cultivars of sweet potato with different flesh colors were investigated using Folin-Ciocalteu's phenol reagent method and Ames test, respectively. There was a remarkable cultivar difference in the polyphenolic content of sweet potato. Su, Hayanmi and Shinhwangmi among 17 cultivars of non-purple sweet potato had higher polyphenolic contents of 21.4, 21.5 and $20.3{\mu}g$ (GAE/g dried sweet potato), respectively, whereas Manami and Yeonhwangmi were very much lower at 4.6 and $4.8{\mu}g$. Mokpo No.62, Borami, Sinjami, Jami and Ayamurasaki had much higher polyphenolic contents of 67.7, 76.9, 44.9, 128.3 and $93.2{\mu}g$, respectively, than non-purple sweet potato. The methanol extract from the sweet potato effectively inhibited the reverse mutation induced by 1-NP, daunomycin, Trp-P-1, Trp-P-2 and 2-AA on S. Typhimurium TA 98, and by 1-NP on S. Typhimurium TA 100. These results suggest that the antimutagencity properties may be influenced by the tested mutagen and strain rather than the polyphenolic content of non-purple and purple sweet potato. However, in the purple sweet potatoes, a high polyphenolic content may influence the antimutagencity properties.

• Archives of Pharmacal Research
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• v.28 no.7
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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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• v.31 no.1
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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.

• Proceedings of the PSK Conference
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• 2003.10b
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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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• v.10 no.2
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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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• v.33 no.4
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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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• v.25 no.5
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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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• v.8 no.2
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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.

• Journal of Life Science
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• v.24 no.6
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• pp.700-706
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• 2014

Doxorubicin (trade name adriamycin), an anthracycline antibiotic, is commonly used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, and soft tissue sarcomas. It is closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA. Its most serious adverse effect is life-threatening heart damage. Its anti-metastatic mechanisms in human prostate carcinomas are not fully understood. In this study, we used LNCap human prostate carcinoma cells to investigate the inhibitory effects of doxorubicin on cell motility and invasion, two critical cellular processes that are often deregulated during metastasis. Doxorubicin treatment inhibited cell migration and invasiveness of LNCap cells without showing any toxicity. Doxorubicin treatment also suppressed the activity and expression of matrix metalloproteinase (MMP)-2 and MMP-9, which were associated with up-regulated expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in LNCap cells. Doxorubicin treatment also attenuated the expression levels of claudin family members (claudin-1, -2,-3 and -4), major components of tightening of tight junctions (TJs) and increased the tightening of TJs, as demonstrated by an increase in transepithelial electrical resistance. The present findings demonstrate that doxorubicin reduces the migration and invasion of prostate carcinomas LNCap cells by modulating the activity of TJs and MMPs.