• Proceedings of the Plant Resources Society of Korea Conference
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• v.18 no.1
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• pp.41-51
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• 2005

We examined whether extracts from 14 local citrus spp. on Jeju Island (Korea) contained chemosensitizing activity that would increase the cytotoxic effect of vincristine(VCR) in drug-resistant cancer cells. We report that methanol extracts from fruits and flowers of some species had a chemosensitizing effect that reversed P-glycoprotein (Pgp)-mediated multidrug resistance (MDR). Using drug-sensitive AML-2/WT and drug-resistant AML-2/D100 in the absence of VCR in human acute myelogenous leukemia cells we found that fruit or flower extracts alone generally had low cytotoxicity $(IC_{50}>200\;{\mu}g/ml)$. In studies examining the effect of extracts on 120 ng/ml VCR cytotoxicity in drug-resistant AML-2/D100 cells, we found that immature fruit extracts had greater chemosensitizing activity than either extracts from mature fruit or flower. Of the 14 species examined, the immature fruit extract from Inchangkyool (Citrus ichangiensis) showed the hishest chemosensitizing index(CI) valus. Immature fruit extracts of Hongkyool(C. tachibana), Byungkyool(C. platymamma), Cheongkyool(C. nippokoreana) and Jinkyool (C. sunki) also strongly potentiated VCR cytotoxicity in AML-2/D100 cells. The chemosensitizing effect of peel extracts was 2-10-fold that of whole fruit extracts from Hongkyool (C. tachibana), Byungkyool (C. platymamma) and Inchangkyool (C. inchangiensis). The CI values for flower extracts were higher than those for mature fruit extracts, but lower than those for immature fruit extracts. These results indicate that immature citrus fruits contain compounds that do not exert their activity solely through cytotoxicity. In particular, Incahngkyool (C. inchangiensis), Byungkyool(C.platymamma), Cheongkyool(C. nippokoreana) and Hongkyool (C. tahibana) may be useful sources of chemosensitizing compounds.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2003.04a
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• pp.102-102
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• 2003

The present study has been undertaken to characterize availability of camellia(Camellia japonica L.) as a medicinal plant with antineoplastic and chemosensitizing activities. The crude extracts from fresn camellia flower, young leaves and nutraceutical tea of camellia leaf and flower buds were evaluated on their potential activities against various human cancer cells and multidrug resistance to cancer cells in vitro. The range of cytotoxicity displayed from 120$\mu\textrm{g}$/mL to 200$\mu\textrm{g}$/mL. Catemix 1(CT-1) mixed with camellia and green tea showed high toxicity(respectively IC$\sub$50/=l16$\mu\textrm{g}$/mL, 129$\mu\textrm{g}$/mL) against AML-2/WT, acute myelogenous leukemia cell and MCF-7, brest adenocarcinoma pleual effusion cell. Generally camellia tea mixed with green tea showed higher cytotoxicity than the other camellia teas mixed with some herbs(CH). Methanol extract of steamed camellia tea and roasted camellia tea had a chemosensitizing effect to reverse Pgp-mediated MDR. In addition, camellia flower tea of insignificant cytotoxicity, chemosensitizing effect were increased remarkably chemosensitizing effect in mixed flower tea with some herbs.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.85-85
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• 2003

This study has been undertaken to increase availability of native camellia in Jeonnam as a medicinal resource and to isolate the effective components from them. Multidrug resistance(MDR) by tumor cells is a major obstacle to successful cancer chemotherapy. We report that the crude extracts of camellia flowers, leaves has a chemosensitizing effect that can reverse Pgp-mediated MDR by increasing the intracellular accumulation of drugs. The cytotoxic and chemosensitizing effects of MeOH extract from 12 spp. citrus fruits on the AML-2/D100 were determined using MTT assay. Chemosensitizing effects was screened in the presence of vincristine, a good substrate of Pgp. IC$\sub$50/ for extracts in AML-2/WT was found to be 65∼350$\mu\textrm{g}$/$m\ell$ whereas the range of its mean IC$\sub$50/ value in Pgp-overexpressing cells (AML-2/Dl00) in the presence of vincristine was 90∼400$\mu\textrm{g}$/$m\ell$. Of the extracts tested, mature leaf extract displayed the most potent chemosensitizing effect［IC$\sub$50/;100 $\mu\textrm{g}$/$m\ell$, CR;1.06, RF;2.97 in the presence of VCR］. This indicates that the toxicity (IC$\sub$50/;288.89$\mu\textrm{g}$/$m\ell$) of mature leaf extract is minimal at concentrations required for a complete reversal of the drug resistance. Also, this result indicates that crude extracts of camellia mature leaves would contain some principles which have chemosensitizing activity.

• Journal of Pharmaceutical Investigation
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• v.40 no.5
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• pp.269-275
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• 2010

P-gp plays a critical role in drug disposition and represents a mechanism for the development of multidrug resistance. Flavonoids, a major class of natural compounds widely present in foods and herbal products, have been shown to inhibit P-gp. Therefore, the aim of this study was to identify new candidate chemosensitizers by screening various plant extracts. The ability of natural plant extracts to inhibit P-gp activity was assessed by measuring cellular accumulation of calcein AM, daunorubicin and vincristine in P-gp overexpressing MDCKII-MDR1 cells. Among more than 800 plant extracts, eight were found to inhibit P-gp activity. Curcuma aromatica extract produced greatest inhibition, followed by Curcuma longa and Dalbergia odorifera extracts. Extracts of Aloe ferox, Curcuma zedoariae rhizome, Zanthoxylum planispinum, and Ageratum conyzoides showed moderate inhibitory effects. Curcumin and quercetin exhibited similar inhibition of P-gpmediated efflux of daunorubicin and vincristine, and flavones had a lesser effect. When chemosensitizing effect was evaluated by measuring daunorubicin sensitivity to MDCKII-MDR1 cells in the presence of natural plant extracts, Curcuma aromatica showed the most potent chemosensitizing effect based on daunorubicin cytotoxicity. In conclusion, natural plant extracts such as Curcuma aromatica can potently inhibit P-gp activity and may have potential as a novel chemosensitizers.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2005.11a
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• pp.173-173
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• 2005

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.3
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• pp.487-493
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• 2004

This study has been undertaken to increase availability of native camellia in Jeonnam as a medicinal resource and to isolate the effective components from them. Fresh leaf and flower of camellia, single camellia tea and camellia tea mixed with green tea, herbs were screened for cytotoxicity on MCF -7 (human breast adenocarcinoma pleual effusion), Calu-6 (human pulmonary carcinoma), SNU-601 (human gastric carcinoma) cells. Also their multidrug-resistance reversing activity were evaluated using drug sensitive AML-2/WT and multidrug-resistant AML-2/D100 cells. Among the camellia extracts, young leaf and camellia tea mixed with green tea had strong growth inhibitory effects in below 100 $\mu\textrm{g}$/mL against human cancer cells. In result, young leaf showed the strongest inhibitory effects on MCF -7 ($IC_{50}$/ = 100 $\mu\textrm{g}$/mL ↑), Calu-6 ($IC_{50}$/ = 79 $\mu\textrm{g}$/mL), and SNU -601 ($IC_{50}$/ = 39 $\mu\textrm{g}$/mL), and AML-2/WT ($IC_{50}$/ = 64 $\mu\textrm{g}$/mL). Chemosensitizing effect was the extracts of mature leaf ($IC_{50}$/ = 97 $\mu\textrm{g}$/mL, RF=3.0), roasted tea ($IC_{50}$/ = 76 $\mu\textrm{g}$/mL, RF = 2.6 ↑) and steam tea ($IC_{50}$/ = 70 $\mu\textrm{g}$/mL, RF=2.8 ↑) strongly potentiate vincristine cytotoxicity in AML-2/D100 cells. But their cytotoxicities to both sensitive AML-2/WT and resistant AML-2/D100 cells were in the same order of magnitude. This results indicate that crude extracts of camellia mature leaves would contain some principles which have chemosensitizing activity.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.3
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• pp.145-155
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• 2022

Multidrug resistance of tumors has been a severe obstacle to the success of cancer chemotherapy. The study wants to investigate the reversal effects of imperatorin (IMP) on doxorubicin (DOX) resistance in K562/DOX leukemia cells, A2780/Taxol cells and in NOD/SCID mice, to explore the possible molecular mechanisms. K562/DOX and A2780/Taxol cells were treated with various concentrations of DOX and Taol with or without different concentrations of IMP, respectively. K562/DOX xenograft model was used to assess anti-tumor effect of IMP combined with DOX. MTT assay, Rhodamine 123 efflux assay, RT-PCR, and Western blot analysis were determined in vivo and in vitro. Results showed that IMP significantly enhanced the cytotoxicity of DOX and Taxol toward corresponding resistance cells. In vivo results illustrated both the tumor volume and tumor weight were significantly decreased after 2-week treatment with IMP combined with DOX compared to the DOX alone group. Western blotting and RT-PCR analyses indicated that IMP downregulated the expression of P-gp in K562/DOX xenograft tumors in NOD/SCID mice. We also evaluated glycolysis and glutamine metabolism in K562/DOX cells by measuring glucose consumption and lactate production. The results revealed that IMP could significantly reduce the glucose consumption and lactate production of K562/DOX cells. Furthermore, IMP could also remarkably repress the glutamine consumption, α-KG and ATP production of K562/DOX cells. Thus, IMP may sensitize K562/DOX cells to DOX and enhance the antitumor effect of DOX in K562/DOX xenograft tumors in NOD/SCID mice. IMP may be an adjuvant therapy to mitigate the multidrug resistance in leukemia chemotherapy.

• 한국균학회소식:학술대회논문집
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• 2018.05a
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• pp.44-44
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• 2018

Fusarium head blight (FHB) caused by infection with Fusarium graminearum leads to enormous losses to crop growers, and may contaminate grains with a number of Fusarium mycotoxins that pose serious risks to human and animal health. Antagonistic bacteria that are used to prevent FHB offer attractive alternatives or supplements to synthetic fungicides for controlling FHB without the negative effects of chemical management. Out of 500 bacterial strains isolated from soil, Bacillus amyloliquefaciens JCK-12 showed strong antifungal activity and was considered a potential source for control strategies to reduce FHB. B. amyloliquefaciens JCK-12 produces several cyclic lipopeptides (CLPs) including iturin A, fengycin, and surfactin. Iturin A inhibits spore germination of F. graminearum. Fengycin or surfactin alone did not display any inhibitory activity against spore germination at concentrations less than 30 ug/ml, but a mixture of iturin A, fengycin, and surfactin showed a remarkable synergistic inhibitory effect on F. graminearum spore germination. The fermentation broth and formulation of B. amyloliquefaciens JCK-12 strain reduced the disease incidence of FHB in wheat. Furthermore, co-application of B. amyloliquefaciens JCK-12 and chemical fungicides resulted in synergistic in vitro antifungal effects and significant disease control efficacy against FHB under greenhouse and field conditions, suggesting that B. amyloliquefaciens JCK-12 has a strong chemosensitizing effect. The synergistic antifungal effect of B. amyloliquefaciens JCK-12 and chemical fungicides in combination may result from the cell wall damage and altered cell membrane permeability in the phytopathogenic fungi caused by the CLP mixtures and subsequent increased sensitivity of F. graminearum to fungicides. In addition, B. amyloliquefaciens JCK-12 showed the potential to reduce trichothecenes mycotoxin production. The results of this study indicate that B. amyloliquefaciens JCK-12 could be used as an available biocontrol agent or as a chemosensitizer to chemical fungicides for controlling FHB disease and as a strategy for preventing the contamination of harvested crops with mycotoxins.

• Toxicological Research
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• v.24 no.1
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• pp.29-36
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• 2008

The present study investigated the anti-proliferative and chemosensitizing effects of Crinum asiaticum var. japonicum against multi-drug resistant (MDR) cancer cells. The 80% methanol extract, chloroform ($CHCl_3$) fraction and butanol (BuOH) fraction of C. asiaticum inhibited the growth of mitoxantrone (MX) resistant HL-60 (HL-60/MX2) cells. When HL-60/MX2 cells were treated with the $CHCl_3$ and BuOH fractions, DNA ladder and sub-G1 hypodiploid cells were observed. Furthermore, the fractions reduced BcI-2 mRNA levels, whereas Bax mRNA levels were increased. These results suggest that the inhibitory effect of C. asiaticum on the growth of the HL-60/MX2 cells might arise from the induction of apoptosis. Treatment of HL-60/MX2 cells with the fractions markedly decreased the mRNA levels of the multi-drug resistance protein-1 and breast cancer resistance protein. The $CHCl_3$ fraction and hexane fraction increased MX accumulation in HL-60/MX2 cells. These results imply that the $CHCl_3$ fraction of C. asiaticum plays a pivotal role as a chemosensitizer. We suggest that components of C. asiaticum might have a therapeutic potential for the treatment of MDR leukemia.