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K G Ramawat - One of the best experts on this subject based on the ideXlab platform.
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Growth retardants stimulate Guggulsterone production in the presence of fungal elicitor in fed-batch cultures of Commiphora wightii
Plant Biotechnology Reports, 2010Co-Authors: S. Suthar, K G RamawatAbstract:Guggulsterone, a hypolipidemic natural agent, is produced in resin canals of the plant Commiphora wightii . In this study, the stimulatory effects of growth retardants [ALAR ( N , N -dimethylaminosuccinamic acid) and CCC (chlormequat chloride)] and fungal elicitor on Guggulsterone accumulation in cell cultures of C. wightii are reported. CCC at 1 mg l^−1 enhanced Guggulsterone content (~123 μg l^−1) when added on the fifth day after inoculation, while ALAR at 2.5 mg l^−1 increased Guggulsterone content (~116 μg l^−1) when added on the tenth day. In a two-stage fed-batch process, combined treatment with fungal elicitor and growth retardant caused a significant increase (~353 μg l^−1) in Guggulsterone content in cell cultures after 17 days of growth. This represents an approximately fivefold increase over the Guggulsterone contents in initial cultures of this plant.
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improved Guggulsterone production from sugars precursors and morphactin in cell cultures of commiphora wightii grown in shake flasks and a bioreactor
Plant Biotechnology Reports, 2008Co-Authors: Meeta Mathur, K G RamawatAbstract:Cell cultures of Commiphora wightii (Arnott.) Bhandari were grown in shake flasks and a bioreactor and an increase in Guggulsterone accumulation up to 18 μg l−1 was recorded in cells grown in the production medium containing a combination of sucrose:glucose (4% total), precursors (phenylalanine, pyruvic acid, xylose, and sodium acetate), morphactin, and 2iP. A yield of 10 g l−1 biomass and ∼200 μg l−1 Guggulsterone was recorded in a 3-l flask and in a 2-l stirred tank bioreactor compared with 6.6 g biomass and 67 μg l−1 Guggulsterone in 250-ml flasks. Increased vessel size was correlated with increased biomass and Guggulsterone accumulation. 2iP alone was not effective for biomass and Guggulsterone accumulation in cell cultures of C. wightii.
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Guggulsterone a potent natural hypolipidemic agent from commiphora wightii problems perseverance and prospects
2008Co-Authors: K G Ramawat, M Marthur, Sahab Dass, Surindra SutharAbstract:Two isomers of Guggulsterone, -E and -Z, have been established as bioactive molecules responsible for the lipid- and cholesterol-lowering activities of oleogum-resin of Commiphora wightii (Arnott.)Bhandari (syn. C. mukul). Guggulsterone is a safe and effective natural product for hypercholesterolemia that has been used as such for the past 3000 years in Ayurveda. It is obtained from a very slow growing desert tree endemic to the Thar Desert and has become endangered due to its over exploitation. Oleogum-resin is a complex mixture of several classes of compounds including gum, minerals, essential oils, sterols, flavanones, and sterones. Early chemical and pharmacological work was carried out in India, but after approval by the United States Food and Drug Administration as a food supplement, several reports describe a role for Guggulsterone in the excretion of cholesterol, involving the farnesoid X receptor, pregnane X receptor, Cyp-7A1 gene, and the bile salt export pump. Biotechnological approaches have been made to develop micropropagation methods through axillary bud break and somatic embryogenesis, as well as Guggulsterone production through cell cultures grown in shake flasks and bioreactors. Field-grown plants show genetic variations, as evident by randomly amplified polymorphic DNA fingerprinting. This review summarizes the research already carried out and that needs to be done to elucidate the biosynthetic pathway, mechanism of action, and biotechnological production of Guggulsterone through cell cultures before commercialization of the molecule as a drug.
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Guggulsterone: a Potent Natural Hypolipidemic Agent from Commiphora wightii – Problems, Perseverance, and Prospects
Bioactive Molecules and Medicinal Plants, 2008Co-Authors: K G Ramawat, M Marthur, Sahab Dass, Surindra SutharAbstract:Two isomers of Guggulsterone, -E and -Z, have been established as bioactive molecules responsible for the lipid- and cholesterol-lowering activities of oleogum-resin of Commiphora wightii (Arnott.)Bhandari (syn. C. mukul). Guggulsterone is a safe and effective natural product for hypercholesterolemia that has been used as such for the past 3000 years in Ayurveda. It is obtained from a very slow growing desert tree endemic to the Thar Desert and has become endangered due to its over exploitation. Oleogum-resin is a complex mixture of several classes of compounds including gum, minerals, essential oils, sterols, flavanones, and sterones. Early chemical and pharmacological work was carried out in India, but after approval by the United States Food and Drug Administration as a food supplement, several reports describe a role for Guggulsterone in the excretion of cholesterol, involving the farnesoid X receptor, pregnane X receptor, Cyp-7A1 gene, and the bile salt export pump. Biotechnological approaches have been made to develop micropropagation methods through axillary bud break and somatic embryogenesis, as well as Guggulsterone production through cell cultures grown in shake flasks and bioreactors. Field-grown plants show genetic variations, as evident by randomly amplified polymorphic DNA fingerprinting. This review summarizes the research already carried out and that needs to be done to elucidate the biosynthetic pathway, mechanism of action, and biotechnological production of Guggulsterone through cell cultures before commercialization of the molecule as a drug.
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Guggulsterone production in cell suspension cultures of the guggul tree commiphora wightii grown in shake flasks and bioreactors
Biotechnology Letters, 2007Co-Authors: Meeta Mathur, K G RamawatAbstract:Cell suspension cultures of Commiphora wightii, grown in modified MS medium containing 2,4-dichlorophenoxyacetic acid (0.5 mg l−1) and kinetin (0.25 mg l−1), produced ∼5 μg Guggulsterone g−1 dry wt. In a 2 l stirred tank bioreactor, the biomass was 5.5 g l−1 and total Guggulsterone was 36 μg l−1.
Ellora Sen - One of the best experts on this subject based on the ideXlab platform.
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Guggulsterone sensitizes glioblastoma cells to sonic hedgehog inhibitor sant 1 induced apoptosis in a ras nfκb dependent manner
Cancer Letters, 2013Co-Authors: Deobrat Dixit, Ruchi Ghildiyal, Nikhil Ponnor Anto, Sourav Ghosh, Vivek Sharma, Ellora SenAbstract:Since Shh pathway effector, Gli1, is overexpressed in gliomas, we investigated the effect of novel Shh inhibitor SANT-1 on glioma cell viability. Though SANT-1 failed to induce apoptosis, it reduced proliferation of glioma stem-like cells. Apart from canonical Shh cascade, Gli1 is also induced by non-canonical pathways including NFκB. Therefore, a combinatorial strategy with Ras/NFκB inhibitor, Guggulsterone, was employed to enhance effectiveness of SANT-1. Guggulsterone inhibited Ras and NFκB activity and sensitized cells to SANT-1 induced apoptosis via intrinsic apoptotic mechanism. Inhibition of either Ras or NFκB activity was sufficient to sensitize cells to SANT-1. Guggulsterone induced ERK activation also contributed to Caspase-9 activation. Since SANT-1 and Guggulsterone differentially target stem-like and non-stem glioma cells respectively, this combination warrants investigation as an effective anti-glioma therapy.
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Guggulsterone sensitizes glioblastoma cells to Sonic hedgehog inhibitor SANT-1 induced apoptosis in a Ras/NFκB dependent manner.
Cancer letters, 2013Co-Authors: Deobrat Dixit, Ruchi Ghildiyal, Nikhil Ponnor Anto, Sourav Ghosh, Vivek Sharma, Ellora SenAbstract:Since Shh pathway effector, Gli1, is overexpressed in gliomas, we investigated the effect of novel Shh inhibitor SANT-1 on glioma cell viability. Though SANT-1 failed to induce apoptosis, it reduced proliferation of glioma stem-like cells. Apart from canonical Shh cascade, Gli1 is also induced by non-canonical pathways including NFκB. Therefore, a combinatorial strategy with Ras/NFκB inhibitor, Guggulsterone, was employed to enhance effectiveness of SANT-1. Guggulsterone inhibited Ras and NFκB activity and sensitized cells to SANT-1 induced apoptosis via intrinsic apoptotic mechanism. Inhibition of either Ras or NFκB activity was sufficient to sensitize cells to SANT-1. Guggulsterone induced ERK activation also contributed to Caspase-9 activation. Since SANT-1 and Guggulsterone differentially target stem-like and non-stem glioma cells respectively, this combination warrants investigation as an effective anti-glioma therapy.
Meeta Mathur - One of the best experts on this subject based on the ideXlab platform.
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improved Guggulsterone production from sugars precursors and morphactin in cell cultures of commiphora wightii grown in shake flasks and a bioreactor
Plant Biotechnology Reports, 2008Co-Authors: Meeta Mathur, K G RamawatAbstract:Cell cultures of Commiphora wightii (Arnott.) Bhandari were grown in shake flasks and a bioreactor and an increase in Guggulsterone accumulation up to 18 μg l−1 was recorded in cells grown in the production medium containing a combination of sucrose:glucose (4% total), precursors (phenylalanine, pyruvic acid, xylose, and sodium acetate), morphactin, and 2iP. A yield of 10 g l−1 biomass and ∼200 μg l−1 Guggulsterone was recorded in a 3-l flask and in a 2-l stirred tank bioreactor compared with 6.6 g biomass and 67 μg l−1 Guggulsterone in 250-ml flasks. Increased vessel size was correlated with increased biomass and Guggulsterone accumulation. 2iP alone was not effective for biomass and Guggulsterone accumulation in cell cultures of C. wightii.
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Guggulsterone production in cell suspension cultures of the guggul tree commiphora wightii grown in shake flasks and bioreactors
Biotechnology Letters, 2007Co-Authors: Meeta Mathur, K G RamawatAbstract:Cell suspension cultures of Commiphora wightii, grown in modified MS medium containing 2,4-dichlorophenoxyacetic acid (0.5 mg l−1) and kinetin (0.25 mg l−1), produced ∼5 μg Guggulsterone g−1 dry wt. In a 2 l stirred tank bioreactor, the biomass was 5.5 g l−1 and total Guggulsterone was 36 μg l−1.
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morphactin influences Guggulsterone production in callus cultures of commiphora wightii
Plant Growth Regulation, 2007Co-Authors: Y S Tanwar, Meeta Mathur, K G RamawatAbstract:Guggulsterone, a hypolipidemic natural agent, is produced in resin canals of the plant Commiphora wightii. In this study, the efficacy of different plant growth regulators was evaluated for optimizing its production. Morphactin was found to be effective in enhancing the accumulation of Guggulsterones in callus cultures. Maximum callus growth was recorded on medium containing morphactin (0.1 mg l−1) and 2iP (2.5 mg l−1), whereas maximum Guggulsterone production occurred when the calluses were cultured on medium containing 0.1 mg l−1 morphactin and 1.0 mg l−1 2iP. Morphactin and 2iP interacted significantly to enhance the callus growth and Guggulsterone production by about 8-folds in one-year-old cultures. However, the effect of morphactin on callus growth and Guggulsterone production was not uniform over the levels of 2iP tested. Such an effect of morphactin has never been reported on the production of secondary metabolites.
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somatic embryo proliferation in commiphora wightii and evidence for Guggulsterone production in culture
IJBT Vol.5(2) [April 2006], 2006Co-Authors: Sandeep Kumar, Meeta Mathur, A K Jain, K G RamawatAbstract:A method for obtaining somatic embryos consistently in Commiphora wightii (Arnott.) Bhandari has been developed. Somatic embryos when sub-cultured on modified MS medium containing ABA (10 µg L -1 ) produced more embryos directly by meristematic activity of the epidermal and subepidermal cells at the hypocotyl region or also from the root tip region. Embryo proliferation was also observed on auxin-cytokinin free modified MS medium supplemented with different concentrations of activated charcoal, abscisic acid, mannitol and sucrose. Modified MS hormone-free medium containing activated charcoal 0.5 g L -1 and sucrose 10 g L -1 was most suitable for multiplication and maturation of embryos. Embryo formation was also recorded from callus produced by earlier formed somatic embryos (indirect). Embryos obtained from various maturation treatments when desiccated under laminar airflow bench for 5-9 d showed maximum germination percentage. Guggulsterone-E and -Z contents of in vitro embryonic cultures were ¼ - and ½ -fold of that found in zygotic embryos, but several fold higher than callus cultures, therefore, hold promise for the production of bioactive Guggulsterones.
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somatic embryo proliferation in commiphora wightii and evidence for Guggulsterone production in culture
IJBT Vol.5(2) [April 2006], 2006Co-Authors: Sandeep Kumar, Meeta Mathur, A K Jain, K G RamawatAbstract:A method for obtaining somatic embryos consistently in Commiphora wightii (Arnott.) Bhandari has been developed. Somatic embryos when sub-cultured on modified MS medium containing ABA (10 µg L -1 ) produced more embryos directly by meristematic activity of the epidermal and subepidermal cells at the hypocotyl region or also from the root tip region. Embryo proliferation was also observed on auxin-cytokinin free modified MS medium supplemented with different concentrations of activated charcoal, abscisic acid, mannitol and sucrose. Modified MS hormone-free medium containing activated charcoal 0.5 g L -1 and sucrose 10 g L -1 was most suitable for multiplication and maturation of embryos. Embryo formation was also recorded from callus produced by earlier formed somatic embryos (indirect). Embryos obtained from various maturation treatments when desiccated under laminar airflow bench for 5-9 d showed maximum germination percentage. Guggulsterone-E and -Z contents of in vitro embryonic cultures were ¼ - and ½ -fold of that found in zygotic embryos, but several fold higher than callus cultures, therefore, hold promise for the production of bioactive Guggulsterones.
Jong-suk Kim - One of the best experts on this subject based on the ideXlab platform.
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Cis-Guggulsterone inhibits the IKK/NF-κB pathway, whereas trans-Guggulsterone inhibits MAPK/AP-1 in MCF‑7 breast cancer cells: Guggulsterone regulates MMP‑9 expression in an isomer-specific manner
International journal of molecular medicine, 2012Co-Authors: Eun-mi Noh, Young-rae Lee, Hyun Jo Youn, Sung Hoo Jung, Eun Yong Chung, Hyun Hur, Jong-suk KimAbstract:Νuclear factor-κB (NF-κB) and activator protein-1 (AP-1) are major transcription factors that have been associated with breast cancer metastasis by inducing matrix metalloproteinase-9 (MMP-9) expression. In this study, we investigated the inhibitory effects of Guggulsterone isomers (cis or trans) on 12-O-tetradecanoylpho-bol-13-acetate (TPA)-induced MMP-9 expression. Cis-Guggulsterone inhibited TPA-induced MMP expression by blocking IκB kinase (IKK)/NF-κB signaling, whereas trans-Guggulsterone blocked mitogen-activated protein kinase (MAPK)/AP-1 signaling. Cis-Guggulsterone was more potent than trans-Guggulsterone in the inhibition of TPA-induced MMP-9 expression and invasion of MCF-7 cells. Furthermore, we found that the combination of these isomers exerted an additive effect on the inhibition of MCF-7 cell invasion. These results suggest that Guggulsterone isomers downregulate MMP-9 expression and tumor cell invasion through the isomer-specific suppression of IKK/NF-κB and MAPK/AP-1 activation. In addition, the suppression of MMP-9 expression correlated well with the inhibition of cell invasion.
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Abstract 4218: Guggulsterone controls isomer-specifically TPA-induced MMP-9 expressions of MCF-7 cells: Identification of the cooperative combination of Guggulsterone isomers in inhibition of breast cancer invasiveness
Cancer Chemistry, 2011Co-Authors: Jong-suk Kim, Eun-mi Noh, Jeong-mi Kim, Young-rae Lee, Hyun Jo Youn, Sung Hoo Jung, Soo Mi Kim, Jinny ParkAbstract:Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Guggulsterone [4,17(20)-pregnadiene-3,16-dione], a constituent of Commiphora mukul, is used to treat obesity, diabetes, arthritis, and atherosclerosis. Recently it has been known that guggulesterone isomers (trans or cis) show isomer-specificity in their antileukemic activities in leukemia cells. Here, we investigated whether Guggulsterone isomers differently control 12-O-tetradecanoylpho-bol-13-acetate (TPA)-induced MMP-9 expression, and then the combination of these isomers cooperatively inhibits breast cancer invasiveness. Cis-Guggulsterone inhibited TPA-induced MMP expression through blocking NF-κB signaling, whereas trans-Guggulsterone through blocking MAPK/AP-1 signaling. Cis-Guggulsterone was the more potent than trans-Guggulsterone in inhibition of TPA-induced MMP-9 expression and cell invasion of MCF-7 cells. Furthermore, we found that the combination of these isomers showed addictive effects on inhibition of cell invasion of MCF-7 cells. These results suggest that guggulesterone controls isomer-specifically TPA-induced MMP-9 expressions and cell invasions of MCF-7 cells. This study is the first to show that combination of Guggulsterone isomers might be known as a potential strategy for the medical treatment of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4218. doi:10.1158/1538-7445.AM2011-4218
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Guggulsterone blocks IL-1beta-mediated inflammatory responses by suppressing NF-kappaB activation in fibroblast-like synoviocytes.
Life sciences, 2008Co-Authors: Young-rae Lee, Jong-suk Kim, Eun-mi Noh, Mi-young Song, Eun-kyung Kim, Jin-woo Park, Ji-hyun Lee, Won-seok Jung, Sung-joo Park, Kang-beom KwonAbstract:Guggulsterone is a plant sterol that is used to treat hyperlipidemia, arthritis, and obesity. Although its anti-inflammatory and anti-hyperlipidemic effects have been well documented, the effect of Guggulsterone on fibroblast-like synoviocytes (FLS) has not yet been reported. Therefore, in this study, the effect of Guggulsterone on interleukin (IL)-1beta-induced inflammatory responses in the FLS of rheumatic patients was investigated. Treatment of FLS with IL-1beta induced production of chemokines such as RANTES and ENA-78. In addition, Western blot analysis and gelatin zymography revealed that IL-1beta activated matrix metalloproteinase (MMP)-1 and -3 in FLS. However, pre-incubation with Guggulsterone completely inhibited the ability of IL-1beta to induce the production of chemokines and to activate MMPs. Although the NF-kappaB binding activity and nuclear p50 and p65 subunit levels, as well as IkappaBalpha degradation in the cytoplasm was greater in cells stimulated with IL-1beta than in unstimulated cells, treatment with Guggulsterone abolished all of these increases. Collectively, these results suggest that Guggulsterone would be useful as an inhibitor of joint destruction in patients with rheumatoid arthritis.
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Guggulsterone blocks IL-1β-mediated inflammatory responses by suppressing NF-κB activation in fibroblast-like synoviocytes
Life Sciences, 2008Co-Authors: Young-rae Lee, Jong-suk Kim, Eun-mi Noh, Mi-young Song, Eun-kyung Kim, Jin-woo Park, Ji-hyun Lee, Won-seok Jung, Sung-joo Park, Kang-beom KwonAbstract:Abstract Guggulsterone is a plant sterol that is used to treat hyperlipidemia, arthritis, and obesity. Although its anti-inflammatory and anti-hyperlipidemic effects have been well documented, the effect of Guggulsterone on fibroblast-like synoviocytes (FLS) has not yet been reported. Therefore, in this study, the effect of Guggulsterone on interleukin (IL)-1β-induced inflammatory responses in the FLS of rheumatic patients was investigated. Treatment of FLS with IL-1β induced production of chemokines such as RANTES and ENA-78. In addition, Western blot analysis and gelatin zymography revealed that IL-1β activated matrix metalloproteinase (MMP)-1 and -3 in FLS. However, pre-incubation with Guggulsterone completely inhibited the ability of IL-1β to induce the production of chemokines and to activate MMPs. Although the NF-κB binding activity and nuclear p50 and p65 subunit levels, as well as IκBα degradation in the cytoplasm was greater in cells stimulated with IL-1β than in unstimulated cells, treatment with Guggulsterone abolished all of these increases. Collectively, these results suggest that Guggulsterone would be useful as an inhibitor of joint destruction in patients with rheumatoid arthritis.
Xiaping Mao - One of the best experts on this subject based on the ideXlab platform.
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Guggulsterone of commiphora mukul resin reverses drug resistance in imatinib resistant leukemic cells by inhibiting cyclooxygenase 2 and p glycoprotein
Phytomedicine, 2014Co-Authors: Xiaping MaoAbstract:The purpose of this study was to investigate the effects of Guggulsterone on cyclooxygenase-2 and P-glycoprotein mediated drug resistance in imatinib-resistant K562 cells (K562/IMA). MTT cytotoxicity assay, flow cytometry, western blot analysis, and ELISA were performed to investigate the anti-proliferative effect, the reversal action of drug resistance, and the inhibitory effect on cyclooxygenase-2, P-glycoprotein, BCR/ABL kinase, and PGE2 release in K562/IMA cells by Guggulsterone. The results showed that co-administration of Guggulsterone resulted in a significant increase in chemo-sensitivity of K562/IMA cells to imatinib, compared with imatinib treatment alone. Rhodamine123 accumulation in K562/IMA cells was significantly enhanced after incubation with Guggulsterone (60, 120 μM), compared with untreated K562/IMA cells (p<0.05). When imatinib (1 μM) was combined with Guggulsterone (60, 120 μM), the mean apoptotic population of K562/IMA cells was 15.47% and 24.91%. It was increased by 3.82 and 6.79 times, compared with imatinib (1 μM) treatment alone. Furthermore, Guggulsterone had significantly inhibitory effects on the levels of cyclooxygenase-2, P-glycoprotein and prostaglandin E2. However, Guggulsterone had little inhibitory effect on the activity of BCR/ABL kinase. The present study indicates Guggulsterone induces apoptosis by inhibiting cyclooxygenase-2 and down-regulating P-glycoprotein expression in K562/IMA cells.
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Guggulsterone of Commiphora mukul resin reverses drug resistance in imatinib-resistant leukemic cells by inhibiting cyclooxygenase-2 and P-glycoprotein.
Phytomedicine : international journal of phytotherapy and phytopharmacology, 2014Co-Authors: Xiaping MaoAbstract:The purpose of this study was to investigate the effects of Guggulsterone on cyclooxygenase-2 and P-glycoprotein mediated drug resistance in imatinib-resistant K562 cells (K562/IMA). MTT cytotoxicity assay, flow cytometry, western blot analysis, and ELISA were performed to investigate the anti-proliferative effect, the reversal action of drug resistance, and the inhibitory effect on cyclooxygenase-2, P-glycoprotein, BCR/ABL kinase, and PGE2 release in K562/IMA cells by Guggulsterone. The results showed that co-administration of Guggulsterone resulted in a significant increase in chemo-sensitivity of K562/IMA cells to imatinib, compared with imatinib treatment alone. Rhodamine123 accumulation in K562/IMA cells was significantly enhanced after incubation with Guggulsterone (60, 120 μM), compared with untreated K562/IMA cells (p
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Guggulsterone regulates the function and expression of P-glycoprotein in rat brain microvessel endothelial cells.
European journal of pharmacology, 2013Co-Authors: Xian-zhen Chen, Xiaping MaoAbstract:Our previous studies found that Guggulsterone could inhibit P-glycoprotein-mediated multidrug resistance in P-glycoprotein over-expressed human cancer cell lines. However, the effects of Guggulsterone on the ;P-glycoprotein function and expression in rat brain microvessel endothelial cells (rBMECs) are poorly understood. In the present study, we investigated whether Guggulsterone has a modulative effect on the function and expression of P-glycoprotein in rBMECs. rhodamine 123 acts as a good substrate for P-glycoprotein, and agents that block P-glycoprotein have been found to increase the retention of rhodamine in cells. The results showed that the accumulation of rhodamine 123 in rBMECs was potentiated in a time-dependent manner after incubation with 30, 100 μM Guggulsterone (P
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Reversion of P-glycoprotein-mediated multidrug resistance by Guggulsterone in multidrug-resistant human cancer cell lines.
European journal of pharmacology, 2012Co-Authors: Xiaping MaoAbstract:Multidrug resistance (MDR) presents a serious problem in cancer chemotherapy. Our previous studies have shown that Guggulsterone could reverse MDR through inhibiting the function and expression of P-glycoprotein (P-gp). The present study is to further investigate the reversal effects of Guggulsterone on MDR in drug-resistant cancer cell lines. The effects of Guggulsterone on MDR1mRNA gene expression, intracellular pH, P-gp ATPase activity and glucosylceramide synthase (GCS) expression were assessed by RT-PCR, Laser Scanning Confocal Microscope using the pH-sensitive fluorescent probe BCECF-AM, Pgp-Glo assay system, and flow cytometric technology, respectively. The results showed that Guggulsterone ranging from 2.5 to 80 μM significantly promoted the activity of P-gp ATPase in a dose-dependent manner. The intracellular pH of K562/DOX cells was found to be higher than K562 cells. After treatment with Guggulsterone (1, 3, 10, 30, 100 μM), intracellular pH of K562/DOX cells decreased in a dose- and time-dependent manner. However, the present study revealed that Guggulsterone ranging from 3 to 100 μM had little influence on MDR1 gene expression in K562/DOX cells. Further, the isogenic doxorubicin-resistant MCF-7/DOX cells exhibited a 4.9-fold increase in GCS level as compared with parental MCF-7 human breast cancer cells. After treatment with Guggulsterone (0.1, 1, 10 μM) for 48 h, MCF-7/DOX cells were found to have no change of GCS protein expression amount. Guggulsterone might be a potent MDR reversal agent, and its mechanism on MDR needs more research.