• Journal of Pharmaceutical Investigation
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• v.34 no.2
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• pp.95-99
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• 2004

One mechanism which plays a prominent role in development of multi-drug resistance seen in cancer cells is the over-expression of P-glycoprotein (P-gp). It is known that compounds found in vegetables and fruits not only have anticarcinogenic properties but may also modulate P-gp activity. The effect of some dietary components on efflux of daunomycin (DNM), a P-gp substrate, was examined in P-gp over-expressed human uterine sarcoma cell line, MES-SA/DX5. The efflux of DNM from the cells was significantly inhibited by quercetin and verapamil, but not by 1-naphtyl-isothiocyanate (NITC). The $IC_{50}$ values for DNM in MES-SA/DX5 cells were increased by flavonoids (quercetin and fisetin), but not by NITC after 72 hour incubation with dietary constituents. In conclusion, flavonoids may play a role in the modulation of P­-gp activity in human uterine sarcoma cells.

• Natural Product Sciences
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• v.18 no.4
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• pp.239-243
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• 2012

Mushrooms have a long history of use in traditional medicine, and hundreds of novel constituents in mushrooms with miraculous biological properties have been identified recently. Although diverse effects for medicinal use of mushrooms such as anticancer activity are proven, their reversal activities of drug resistance in cancer cells was rarely reported so far. In the search for novel medicinal use of mushrooms, we tested the multidrug resistance (MDR) reversal activities of diverse mushrooms collected from Korea. Among, the mushroom extracts tested, Cantharellus cibarius (M02) and Russula emetica (M12) revealed MDR reversal activities of paclitaxel in the P-glycoprotein (Pgp)-positive HCT15 and MES-SA/dX5 cancer cells, but not in the Pgp-negative A549 and MES-SA cancer cells. In addition, these mushrooms also enhanced the cytotoxicity of doxorubicin, another well-kwown Pgp-associated anticancer drug against MES-SA/DX5 cells, but not against MES-SA cells. Meanwhile, the cytotoxicity of cisplatin, a well-known Pgp-non-associated anticancer drug, was not affected by the mushrooms all the cells tested. From these results, we suspected that some ingredients of M02 and M12 have Pgp-associated MDR reversal activities.

• Bulletin of the Korean Chemical Society
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• v.30 no.4
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• pp.779-780
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• 2009

• Bulletin of the Korean Chemical Society
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• v.30 no.1
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• pp.43-48
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• 2009

The synthesis of coumarin-based natural products and their derivatives is described. In vitro MDR reversal activities of the synthesized compounds were evaluated in P-glycoprotein over-expressing human sarcoma cell line MES-SA/DX5. Some of the coumarin derivatives were found to show potent MDR reversal activity. In particular, pyridyl derivative (15e) exhibited more potency than verapamil.

• Journal of Pharmaceutical Investigation
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• v.35 no.4
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• pp.249-254
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• 2005

Multidrug resistance (MDR) of cancer cells is, at least in part, associated with the overexpression of P-glycoprotein (P-gp). Many studies have demonstrated that natural compounds obtained from fruits, vegetables, teas and medicinal plants may modulate P-gp activity. The objective of the present investigation was to examine the effect of seven natural compounds on the P-gp activity in human uterine sarcoma cell line, MES-SA/DX5. Daunomycin uptake was significantly increased by biochanin A and silymarin (p<0.0001) whereas it was reduced by morin (p<0.01). The efflux of daunomycin from the cells was significantly inhibited by biochanin A, morin, cephalotaxine, berberine (p<0.05) and silymarin (p<0.0001). Biochanin A, berberine and silymarin significantly decreased $IC_{50}$ value of daunomycin (p<0.05) while morin increased it (p<0.05). These results suggest that some natural compounds such as biochanin A and silymarin may inhibit P-gp function and can be developed as MDR reversing agents to improve the efficacy of chemotherapeutic drugs when administered concomitantly.

• 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)

• Korean Journal of Pharmacognosy
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• v.39 no.4
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• pp.347-351
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• 2008

The methanol (MeOH) extract of the rhizome of Alpinia officinarum Hance (Zingiberaceae) demonstrated a potent inhibition on the proliferation of cultured human tumor cell lines such as MES-SA (human uterine carcinoma cell line), MESSA/DX5 (multidrug resistant subline of MES-SA), HCT-15 (human colorectal adenocarcinoma cell line), HCT15/CL02 (multidrug resistant subline of HCT15). The MeOH extract was fractionated into four portions by serial solvent partition, ie., methylene chloride (CH2Cl2) soluble part, ethylacetate (EtOAc) soluble part, n-butanol (BuOH) soluble part and remaining water layer. Among them, the $CH_2Cl_2$ soluble part of the extract exhibited a most potent inhibition on the proliferation of tested tumor cell lines. Bioassay-guided fractionation of the $CH_2Cl_2$ soluble part led to the isolation of five diarylheptanoid and two flavonoid constituents, i. e., galangin (1), 7-(4"-hydroxy-3"-methoxyphenyl)-1-phenylhept-4-en-3-one (2), 1,7-diphenyl-5-hydroxy-3-heptanone (3), trans,trans-1-(3'-methoxy-4'-hydroxyphenyl)-7-phenyl-5-ol-4,6-dien-3-heptanone (4), 5-methoxy-7-(4"-hydroxy-3"-methoxyphenyl)-1-phenyl-3-heptanone (5), kaempferide (6), 5-hydroxy-7-(4"-hydroxy-3"-methoxyphenyl)-1-phenyl-3-heptanone (7). Structures of the isolated active components (1 - 7) were established by chemical and spectroscopic means.

• 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.

• Archives of Pharmacal Research
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• v.29 no.9
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• pp.757-761
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• 2006

Six protoberberine alkaloids were isolated from the chloroform layer of the rhizome of Coptis japonica Makino (Ranunculaceae). The structures of the isolated compounds were determined to be 6-([1,3]dioxolo[4,5-g]isoquinoline-5-carbonyl)-2,3-dimethoxy-benzoic acid methyl ester (1), oxyberberine (2), 8-oxo-epiberberine (3), 8-oxocoptisine (4), berberine (5) and palmatine (6) by physicochemical and spectroscopic methods. The compound 3 (8-oxo-epiberberine) was first isolated from natural sources. The compounds were tested for cytotoxicity against five tumor cell lines in vitro by SRB method, and also tested for the MDR reversal activities. Compound 4 was of significant P-gp MDR inhibition activity with ED50 value $0.018\;{\mu}g/mL$ in MES-SA/DX5 cell and $0.0005\;{\mu}g/mL$ in HCT15 cell, respectively.

• 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.