RESUMO
Fucoidan, a sulfated polysaccharide, has various biological activities, such as anticancer, antiangiogenic and antiinflammatory effects; however, the mechanisms of action of fucoidan on anticancer activity have not been fully elucidated. The anticancer effects of fucoidan from Undaria pinnatifida on A549 human lung carcinoma cells were examined. Treatment of A549 cells with fucoidan resulted in potent antiproliferative activity. Also, some typical apoptotic characteristics, such as chromatin condensation and an increase in the population of sub-G1 hypodiploid cells, were observed. With respect to the mechanism underlying the induction of apoptosis, fucoidan reduced Bcl-2 expression, but the expression of Bax was increased in a dose-dependent manner compared with the controls. Furthermore, fucoidan induced caspase-9 activation, but decreased the level of procaspase-3. Cleavage of poly-ADP-ribose polymerase (PARP), a vital substrate of effector caspase, was found. The study further investigated the role of the MAPK and PI3K/Akt pathways with respect to the apoptotic effect of fucoidan, and showed that fucoidan activates ERK1/2 in A549 cells. Unlike ERK1/2, however, treatment with fucoidan resulted in the down-regulation of phospho-p38 expression. In addition, fucoidan resulted in the down-regulation of phospho-PI3K/Akt. Together, these results indicate that fucoidan induces apoptosis of A549 human lung cancer cells through down-regulation of p38, PI3K/Akt, and the activation of the ERK1/2 MAPK pathway.
Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Polissacarídeos/farmacologia , Undaria/química , Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/patologiaRESUMO
Recently, it was reported that in a 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model, neuronal cell death is associated with the cdk5-mediated hyperphosphorylation of myocyte enhancer factor 2 (MEF2), a transcription factor that is critically required for neuronal survival. In the present study, we investigated the possible involvement of cdk5-mediated MEF2D down-regulation on 6-hydroxydopamine (6-OHDA)-induced PC12 cell death. 6-OHDA was found to significantly increase nitric oxide (NO) production and to induce apoptosis in a time-dependent manner in PC12 cells. Furthermore, 6-OHDA was found to markedly reduce MEF2D levels under conditions that could induce PC12 cell apoptosis. In addition, PC12 cell death and MEF2D degradation by 6-OHDA were prevented by the cdk5 inhibitor roscovitine, but roscovitine could not restore the 6-OHDA-induced inactivation of Akt. These results suggest that the cell death and MEF2D degradation caused by 6-OHDA are dependent on cdk5 activity. On the other hand, roscovitine enhanced the 6-OHDA-induced activations of ERK1/2 and JNK, but reduced the 6-OHDA-induced activation of p38. These results suggest that PC12 cell death by 6-OHDA appears to be regulated by the down-regulation of MEF2D via some interaction between cdk5 and MAP kinase.
Assuntos
Apoptose/efeitos dos fármacos , Fatores de Regulação Miogênica/metabolismo , Oxidopamina/farmacologia , Células PC12/efeitos dos fármacos , Células PC12/fisiologia , Animais , Apoptose/fisiologia , Quinase 5 Dependente de Ciclina/genética , Quinase 5 Dependente de Ciclina/metabolismo , Fragmentação do DNA , Regulação para Baixo , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fatores de Transcrição MEF2 , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fatores de Regulação Miogênica/genética , Óxido Nítrico/metabolismo , Inibidores de Proteínas Quinases/metabolismo , Purinas/metabolismo , Ratos , Roscovitina , Transdução de Sinais/fisiologiaRESUMO
Chromatographic separation resulted in the identification of one new squalene derivative, named lobophytene (1), three cembranoid diterpenes (2-4), and two sterols (5 and 6) from the Vietnamese marine soft coral Lobophytum sp. Their structures were identified on the basis of extensive spectroscopic data and comparison of those with reported data. Compounds 1 and 2 showed significant cytotoxic activities against lung (A549) and colon (HT-29) cell lines with IC(50) values of 8.2 and 5.6 microM for 1; 5.1 and 1.8 microM for 2, respectively.
Assuntos
Antozoários/química , Antineoplásicos , Animais , Antozoários/crescimento & desenvolvimento , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Espectroscopia de Infravermelho com Transformada de Fourier , VietnãRESUMO
Dammarane-type saponins, gypenosides VN1-VN7 (1-7), were isolated from the total saponin extract of Gynostemma pentaphyllum aerial parts, with their structures elucidated on the basis of spectroscopic and chemical methods. These compounds showed moderate cytotoxic activity against four human cancer cell lines, A549 (lung), HT-29 (colon), MCF-7 (breast), and SK-OV-3 (ovary), with IC(50) values ranging from 19.6+/-1.1 to 43.1+/-1.0 microM. Regarding the HL-60 (acute promyelocytic leukemia) cell line, compounds 1, 5, and 6 showed weakly active with IC(50) values of 62.8+/-1.9, 72.6+/-3.6, and 82.4+/-3.2 nM, respectively, while 2, 3, 4, and 7 were less active with IC(50) values>100 microM.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Gynostemma/química , Plantas Medicinais/química , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células HL-60 , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Saponinas/química , Saponinas/farmacologia , Triterpenos/química , Triterpenos/farmacologia , Vietnã , DamaranosRESUMO
Six indirubin derivatives have been synthesized and their inhibitory effects on the growth of HL-60 human promyelocytic leukemia cells investigated. Cell viability was determined using the trypan blue exclusion method. Indirubin-3'-oxime (I-1) inhibited the growth of HL-60 cells with a GI50 value of 36.6 microM, whereas I-0, I-2, I-3, I-4 and I-6 showed only weak cytotoxic activities against HL-60 cancer cells with GI50 values in the range of 97.3 to over 100 microM. These results indicate that indirubin derivatives might be useful candidate agents for exploring potential antileukemic drugs.
Assuntos
Antibióticos Antineoplásicos/química , Células HL-60 , Humanos , Indóis/químicaRESUMO
In our preliminary screening study on the anti-inflammatory activity, a new triterpene compound, aceranol acetate (1), was isolated along with five known compounds: beta-amyrin acetate (2); glutinol acetate (3); friedelin (4); glutinol (5); (3beta)-d-glucopyranoside-stigmast-5-en-3-yl (6), from the stems and leaves of Acer mandshuricum. The structure of the new triterpene was determined to be 5alpha,6alpha-epidioxy-5beta,6beta-epoxy-9,13-dimethyl-25,26-dinoroleanan-3beta-ol acetate by spectroscopic studies. Compounds 2-6 were isolated from this plant for the first. Five triterpene compounds (1-5) showed significant cytotoxic activity with GI(50) in the range of 11.1-17.9microM, whereas steroid compound (6) exhibited moderate activity against four human cancer cell lines (HL-60, SK-OV-3, A549, and HT-29). Furthermore, the anti-inflammatory effects of compounds 1-6 in the non-cytotoxic concentrations (1-100nM) were evaluated for the inhibitory activity of TNF-alpha secretion in the lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophage cell line. Among the compounds tested, compound 2 showed the strongest anti-inflammatory activity with the inhibition rate up to 38.40% at the concentration of 100nM, whereas other five compounds (2-6) exhibited moderate activity.
Assuntos
Acer/química , Anti-Inflamatórios/química , Ácido Oleanólico/análogos & derivados , Triterpenos/química , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/toxicidade , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lipopolissacarídeos/toxicidade , Camundongos , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/toxicidade , Plantas Medicinais/química , Triterpenos/isolamento & purificação , Triterpenos/toxicidade , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Three new lupane triterpene glycosides, acankoreosides J-L ( 1- 3), were isolated from the leaves of Acanthopanax koreanum. Based on the spectroscopic data, the chemical structures were determined as 3 alpha-hydroxy-20-oxo-30-norlupane-23,28-dioic 28- O- alpha- L-rhamnopyranosyl-(1 --> 4)- beta- D-glucopyranosyl-(1 --> 6)- beta- D-glucopyranosyl ester ( 1); 3 alpha,20,29-trihydroxylupane-23,28-dioic 28- O- alpha- L-rhamnopyranosyl-(1 --> 4)- beta- D-glucopyranosyl-(1 --> 6)- beta- D-glucopyranosyl ester ( 2); and (20S)-3 alpha-hydroxy-29,29-dimethoxylupane-23,28-dioic 28- O- alpha- L-rhamnopyranosyl-(1 --> 4)- beta- D-glucopyranosyl-(1 --> 6)- beta- D-glucopyranosyl ester ( 3). Compounds 1- 3 were evaluated for their cytotoxicity and showed moderate activity against four cell lines, A549 (lung), HL-60 (leukemia), MCF-7 (breast), and U937 (leukemia), with IC (50) values of 23.4, 36.5, 22.6, and 18.5 microM for 1; 6.8, 18.6, 23.1, and > 100 microM for 2; and 28.9, 21.8, 11.0, and 27.5 microM for 3, respectively.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Eleutherococcus/química , Glicosídeos/uso terapêutico , Neoplasias/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Triterpenos/uso terapêutico , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Humanos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta , Triterpenos/isolamento & purificação , Triterpenos/farmacologiaRESUMO
This study was conducted to evaluate the effect of Crinum asiaticum, a plant native to Jeju Island, Korea, on the promotion of hair growth. When rat vibrissa follicles were treated with a 95% ethanol (EtOH) extract of C. asiaticum, the hair-fiber lengths of the vibrissa follicles increased significantly. In addition, after daily topical application of the EtOH extract of C. asiaticum onto the back of C57BL/6 mice, anagen progression of the hair shaft was induced. Moreover, the extract increased the proliferation of immortalized vibrissa dermal papilla cells. When the vibrissa follicles in the anagen phase were treated with the extract, immunohistochemical analysis revealed that the extract was found to increase the expression of proliferating cell nuclear antigen (PCNA) in the bulb region of the 7-day cultured follicles. In particular, norgalanthamine, a principal of the extract, showed activity that increased the hair-fiber lengths of vibrissa follicles and the proliferation of dermal papilla cells. These results suggest that norgalanthamine, a principal of C. asiaticum, has the potential to promote hair growth via the proliferation of dermal papilla.
Assuntos
Alcaloides de Amaryllidaceae/farmacologia , Crinum , Galantamina/análogos & derivados , Cabelo/crescimento & desenvolvimento , Extratos Vegetais/farmacologia , Animais , Células Cultivadas , Citoproteção/efeitos dos fármacos , Feminino , Galantamina/farmacologia , Cabelo/efeitos dos fármacos , Folículo Piloso/citologia , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Minoxidil/farmacologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Wistar , VibrissasRESUMO
Six dammarane-type saponins, including three new compounds, floralginsenosides Ta-Tc (1-3), and three known, floralginsenoside Td (4), ginsenoside F(1) (5), and ginsenoside F(5) (6), were isolated from the flower buds of Panax ginseng. Floralginsenoside Td (4) was first isolated from natural plant sources. Their structures were elucidated on the basis of extensive chemical and spectroscopic methods. Compounds 1, 5, and 6 showed cytotoxic activities towards the HL-60 human leukemia cell line with respective IC(50) values of 36.3, 23.2, and 62.4microM. In addition, after the HL-60 cells were treated with these compounds, several apoptosis events, including chromatin condensation and increase in the population of sub-G1 hypodiploid cells, were observed.
Assuntos
Antineoplásicos Fitogênicos/química , Panax/química , Saponinas/química , Triterpenos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/toxicidade , Flores/química , Células HL-60 , Humanos , Leucemia/tratamento farmacológico , Espectroscopia de Ressonância Magnética , Conformação Molecular , Saponinas/isolamento & purificação , Saponinas/toxicidade , DamaranosRESUMO
The antitumor activity of fucoidan from Fucus vesiculosus was investigated in human colon carcinoma cells. The crude fucoidan, a polysaccharide composed predominantly of sulfated fucose, markedly inhibited the growth of HCT-15 cells (human colon carcinoma cells). After HCT-15 cells were treated with fucoidan, several apoptotic events such as DNA fragmentation, chromatin condensation and increase of the population of sub-G1 hypodiploid cells were observed. In the mechanism of fucoidan-induced apoptosis, we examined changes in Bcl-2 and Bax protein expression levels and activation of caspases. Fucoidan decreased Bcl-2 expression, whereas the expression of Bax was increased in a time-dependent manner compared to the control. In addition, the active forms of caspase-9 and caspase-3 were increased, and the cleavage of poly(ADP-ribose) polymerase (PARP), a vital substrate of effector caspase, was observed. Furthermore, the induction of apoptosis was also accompanied by a strong activation of extracellular signal-regulated kinase (ERK) and p38 kinase and an inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt in a time-dependent manner. These findings provide evidence demonstrating that the pro-apoptotic effect of fucoidan is mediated through the activation of ERK, p38 and the blocking of the PI3K/Akt signal pathway in HCT-15 cells. These data support the hypothesis that fucoidan may have potential in colon cancer treatment.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Fucus/química , Extratos Vegetais/uso terapêutico , Polissacarídeos/uso terapêutico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Antineoplásicos Fitogênicos/farmacologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Poli(ADP-Ribose) Polimerases/metabolismo , Polissacarídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
One new lupane-triterpene glycoside, acankoreoside I (1), and four known compounds, acankoreoside A (2), acankoreoside D (3), acankoreoside F (4), and acantrifoside A (5), were isolated from the leaves of Acanthopanax koreanum (Araliaceae). Their chemical structures were elucidated by mass, 1D- and 2D-NMR spectroscopy. The structure of new compound 1 was determined to be 3alpha,11alpha,30-trihydroxylup-23-al-20(29)-en-28-oic acid 28-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl] ester. The cytotoxic activities of these compounds were evaluated with four cancer cell lines such as A-549 (lung), HL-60 (acute promyelocytic leukemia), MCF-7 (breast), and U-937 (leukemia). Compound 1 showed growth inhibitory effect in A-549, HL-60, and MCF-7 cell lines with the IC(50) values of 8.2 microM, 12.1 microM, and 28.6 microM, respectively, whereas it was less active in the U937 cell line (the IC(50) >100 microM).
Assuntos
Antineoplásicos/química , Eleutherococcus/química , Glicosídeos/química , Triterpenos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Glicosídeos/toxicidade , Humanos , Espectroscopia de Ressonância Magnética , Folhas de Planta/química , Triterpenos/farmacologia , Triterpenos/toxicidadeRESUMO
Two new C(29) sterols with a cyclopropane ring at C-25 and C-26, petrosterol-3,6-dione (1) and 5alpha,6alpha-epoxy-petrosterol (2), along with petrosterol (3), were isolated from the Vietnamese marine sponge Ianthella sp. The structures of the new compounds were elucidated by comprehensive spectroscopic analyses. Compounds 1-3 showed cytotoxic activities on A549, HL-60, MCF-7, SK-OV-3, and U937 cancer cell lines with IC(50) in the range of 8.4-22.6 microM, whereas compounds 1-3 exhibited only weak cytotoxic activities on HT-29 cell. After HL-60 cells were treated with the compounds, several apoptosis events like chromatin condensation and the increase of the population of sub-G1 hypodiploid cells were observed. These data supported that the compounds might have potential for leukemia treatment.
Assuntos
Antineoplásicos/química , Poríferos/química , Esteróis/química , Animais , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Linhagem Celular , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Humanos , Esteróis/isolamento & purificação , Esteróis/farmacologia , VietnãRESUMO
Combined chromatographic methods led to the isolation of two new triterpenoid saponins, glochieriosides A and B (1, 2), from the aerial parts of Glochidion eriocarpum, along with three known triterpenes, glochidone (3), lup-20(29)-en-3beta,23-diol (4), and lup-20(29)-en-1beta,3beta-diol (5). The structures of the new saponins were determined to be 22beta-benzoyloxy-3beta,16beta,28-trihydroxyolean-12-ene 3-O-[beta-D-glucopyranosyl-(1-->3)-alpha-L-arabinopyranoside] (1) and 22beta-benzoyloxy-3beta,16beta,28-trihydroxyolean-12-ene 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-xylopyranoside] (2). The structural elucidation was accomplished by using a combination of the 1D-NMR (1H-, 13C-NMR, distortionless enhancement by polarization transfer (DEPT) 90 degrees , and DEPT 135 degrees ), 2D-NMR (1H-1H correlation spectroscopy, heteronuclear multiple quantum correlation, heteronuclear multiple bond correlation, and rotating frame Overhouser effect spectroscopy), ESI-MS, and HR-FAB-MS experiments. Glochieriosides A and B exhibited significant cytotoxic activity against HL-60, HT-29, MCF-7 and SK-OV-3 human cancer cell lines with the IC50 values of 5.5, 6.8, 29.1, and 22.7 microM for glochierioside A, respectively, and 6.6, 18.6, 36.1, and 16.0 microM for glochierioside B. Glochidone was less active with IC50 values greater than 100 microM while lup-20(29)-en-1beta,3beta-diol was moderately active with IC50 values of 43.3, 67.0, 66.1, and 48.0 microM, respectively.
Assuntos
Células/efeitos dos fármacos , Phyllanthus/química , Componentes Aéreos da Planta/química , Extratos Vegetais , Saponinas , Sesquiterpenos/química , Triterpenos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Saponinas/química , Saponinas/farmacologia , Sesquiterpenos/farmacologia , Triterpenos/química , Triterpenos/farmacologiaRESUMO
This study was conducted to evaluate the effect of Schisandra nigra, a plant native to Jeju Island, South Korea, on the promotion of hair growth. When rat vibrissa follicles were treated with 85% ethanol (EtOH) extract of S. nigra, the hair-fiber lengths of the vibrissa follicles increased significantly. In addition, after topical application of the EtOH extract of S. nigra onto the back of C57BL/6 mice every other day, anagen progression of the hair shaft was induced. Moreover, the extract increased both the expression of proliferating cell nuclear antigen (PCNA) in the bulb matrix region and the proliferation of immortalized vibrissa dermal papilla cells. In order to determine the mechanism by which S. nigra promotes hair growth, we examined its relationship with the transforming growth factor-beta2 (TGF-beta2) signal pathway, which is known to be a regulator of catagen induction. When the vibrissa follicles in the anagen phase were treated with S. nigra extract for 7 days, the expression of TGF-beta2 in the bulb matrix region was found to be lower than that of the control follicles that were expected to be in the anagen-catagen transition phase. These results suggest that S. nigra extract has the potential to promote hair growth via down regulation of TGF-beta2 and the proliferation of dermal papilla.
Assuntos
Folículo Piloso/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Extratos Vegetais/farmacologia , Schisandra , Animais , Técnicas de Cultura de Células , Folículo Piloso/metabolismo , Imuno-Histoquímica , Coreia (Geográfico) , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Minoxidil/farmacologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Wistar , Fator de Crescimento Transformador beta2/metabolismoRESUMO
One new C(29) sterol with a cyclopropane ring at C-25 and C-26, aragusteroketal B (1), and aragusterol B (2) were isolated from the Vietnamese marine sponge Ianthella sp. Their structures were elucidated by extensive spectroscopic analyses. Both 1 and 2 showed moderate cytotoxic activity against MCF-7, SK-Hep-1, and HeLa cell lines with IC(50) in the range of 12.8-27.8 microM.
Assuntos
Antineoplásicos/química , Poríferos/química , Esteróis/química , Animais , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromatografia por Troca Iônica , Cromatografia em Camada Fina , Corantes , Humanos , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Conformação Molecular , Espectrofotometria Infravermelho , Esteróis/isolamento & purificação , Esteróis/farmacologia , Sais de Tetrazólio , Tiazóis , VietnãRESUMO
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 (CHCI3) 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 CHCI3 and BuOH fractions, DNA ladder and sub-G1 hypodiploid cells were observed. Furthermore, the fractions reduced Bcl-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 CHCI3 fraction and hexane fraction increased MX accumulation in HL-60/MX2 cells. These results imply that the CHCI3 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.