• Title/Summary/Keyword: synergistic drug combination

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Synergistic Effects of Exemestane and Aspirin on MCF-7 Human Breast Cancer Cells

  • Hu, Li-Xia;Du, Ying-Ying;Zhang, Ying;Pan, Yue-Yin
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5903-5908
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    • 2012
  • Objective: The purpose of this study is to investigate the combined effects of exemestane and aspirin on MCF-7 human breast cancer cells. Methods: Antiproliferative effects of exemestane and aspirin, alone and in combination, on growth of MCF-7 human breast cancer cells were assessed using the MTT assay. Synergistic interaction between the two drugs was evaluated in vitro using the combination index (CI) method. The cell cycle distribution was analyzed by flow cytometry and Western blotting was used to investigate the expression of cyclooxygenase-1, cyclooxygenase-2 and Bcl-2. Results: MTT assays indicated that combination treatment obviously decreased the viability of MCF-7 human breast cancer cells compared to individual drug treatment (CI<1). In addition, the combination of exemestane and aspirin exhibited a synergistic inhibition of cell proliferation, significantly arrested the cell cycle in the $G_0/G_1$ phase and produced a stronger inhibitory effect on COX-1 and Bcl-2 expression than control or individual drug treatment. Conclusion: These results indicate that the combination of exemestane and aspirin might become a useful method to the treatment of hormone-dependent breast cancer. The combination of the two inhibitors significantly increased the response as compared to single agent treatment, suggesting that combination treatment could become a highly effective approach for breast cancer.

Antibacterial Activity of Sophoraflavanone G Isolated from the Roots of Sophora flavescens

  • Cha, Jeong-Dan;Jeong, Mi-Ran;Jeong, Seung-Il;Lee, Kyung-Yeol
    • Journal of Microbiology and Biotechnology
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    • v.17 no.5
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    • pp.858-864
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    • 2007
  • This study investigated the antibacterial activities of sophoraflavanone G from Sophora flavescens in combination with two antimicrobial agents against oral bacteria. The combined effect of sophoraflavanone G and the antimicrobial agents was evaluated using the checkerboard method to obtain a fractional inhibitory concentration(FIC) index. The sophoraflavanone G+ampicillin(AM) combination was found to have a synergistic effect against S. mutans, S. sanguinis, S. sobrinus, S. gordonii, A. actinomycetemcomitans, F nucleatum, P. intermedia, and P. gingivalis, whereas the sophoraflavanone G+gentamicin(GM) combination had a synergistic effect against S. sanguinis, S. criceti, S. anginosus, A. actinomycetemcomitans, F nucleatum, P. intermedia, and P. gingivalis. Neither combination exhibited any antagonistic interactions(FIC index>4). In particular, the MICs/MBCs for all the bacteria were reduced to one-half$\sim$one-sixteenth as a result of the drug combinations. A synergistic interaction was also confirmed by time-kill studies for nine bacteria where the checkerboard suggested synergy. Thus, a strong bactericidal effect was exerted through the drug combinations, plus in vitro data suggested that sophoraflavanone G combined with other antibiotics may be microbiologically beneficial rather than antagonistic.

The Synergistic Anticancer Effect of Artesunate Combined with Allicin in Osteosarcoma Cell Line in Vitro and in Vivo

  • Jiang, Wei;Huang, Yong;Wang, Jing-Peng;Yu, Xiao-Yun;Zhang, Lin-Yi
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.8
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    • pp.4615-4619
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    • 2013
  • Background: Artesunate, extracted from Artemisia annua, has been proven to have anti-cancer potential. Allicin, diallyl thiosulfinate, the main biologically active compound derived from garlic, is also of interest in cancer treatment research. This object of this report was to document synergistic effects of artesunate combined with allicin on osteosarcoma cell lines in vitro and in vivo. Methods: After treatment with artesunate and allicin at various concentrations, the viability of osteosarcoma cells was analyzed by MTT method, with assessment of invasion and motility, colony formation and apoptosis. Western Blotting was performed to determine the expression of caspase-3/9, and activity was also detected after drug treatment. Moreover, in a nude mouse model established with orthotopic xenograft tumors, tumor weight and volume were monitored after drug administration via the intraperitoneal (i.p.) route. Results: The viability of osteosarcoma cells in the combination group was significantly decreased in a concentration and time dependent manner; moreover, invasion, motility and colony formation ability were significantly suppressed and the apoptotic rate was significantly increased through caspase-3/9 expression and activity enhancement in the combination group. Furthermore, suppression of tumor growth was evident in vivo. Conclusion: Our results indicated that artesunate and allicin in combination exert synergistic effects on osteosarcoma cell proliferation and apoptosis.

Synergistic anticancer activity of resveratrol in combination with docetaxel in prostate carcinoma cells

  • Lee, Sang-Han;Lee, Yoon-Jin
    • Nutrition Research and Practice
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    • v.15 no.1
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    • pp.12-25
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    • 2021
  • BACKGROUND/OBJECTIVES: The study was conducted to investigate the efficacy of the combination treatment of phytochemical resveratrol and the anticancer drug docetaxel (DTX) on prostate carcinoma LNCaP cells, including factors related to detailed cell death mechanisms. MATERIALS/METHODS: Using 2-dimensional monolayer and 3-dimensional spheroid culture systems, we examined the effects of resveratrol and DTX on cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential, apoptosis, and necroptosis by MTT, flow cytometry, and Western blotting. RESULTS: At concentrations not toxic to normal human prostate epithelial cells, resveratrol effectively decreased the viability of LNCaP cells depending on concentration and time. The combination treatment of resveratrol and DTX exhibited synergistic inhibitory effects on cell growth, demonstrated by an increase in the sub-G0/G1 peak, Annexin V-phycoerythrin positive cell fraction, ROS, mitochondrial dysfunction, and DNA damage response as well as concurrent activation of apoptosis and necroptosis. Apoptosis and necroptosis were rescued by pretreatment with ROS scavenger N-acetylcysteine. CONCLUSIONS: We report resveratrol as an adjuvant drug candidate for improving the outcome of treatment in DTX therapy. Although the underlying mechanisms of necroptosis should be investigated comprehensively, targeting apoptosis and necroptosis simultaneously in the treatment of cancer can be a useful strategy for the development of promising drug candidates.

Enhanced Anti-tumor Efficacy of Aspirin Combined with Triptolide in Cervical Cancer Cells

  • Chen, Rong-Hui;Tian, Yong-Jie
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3041-3044
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    • 2013
  • Background: The non-steroidal anti-inflammatory drug (NSAID) aspirin (acetylsalicylic acid) is an inhibitor of cyclooxygenase enzymes. Recent studies have shown that aspirin could be used as an anti-tumor drug. Triptolide, the major compound extracted from the Chinese herb Tripteryglum wilfordii Hook.f, has now been shown that it can inhibit tumor growth. The aim of this study was to analyze the anti-tumor efficiency of aspirin and triptolide in cervical cancer cells. Methods: Viability of cervical cancer cell lines was assessed by the MTT method at various concentrations of aspirin and triptolide. Siha and HeLa cell apoptotic analysis was performed by flow cytometry. Real time-PCR and Western Blotting were used to analyze the expression of Bcl-2/Bax, Cyclin D1 and p16. Results: Viability in the combination group was significantly decreased as compared with either drug used alone. Expression change of Bcl-2/Bax, CyclinD1 and p16 appeared to play an important role in the synergistic killing effect on cervical cancer cell apoptosis. Conclusion: Aspirin and triptolide combination treatment may have synergistic anti-tumor effects on cervical cancer cells.

Effect of Korean Red Ginseng Crude Drug-Combined Preparations (RGCDPs) on Memory Enhancement in Mice

  • Wee, Jae-Joon;Kyung, Jong-Soo;Kim, Na-Mi;Song, Yong-Bum;Kwak, Yi-Seong;Park, Jong-Dae
    • Natural Product Sciences
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    • v.11 no.4
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    • pp.189-192
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    • 2005
  • Anti-amnestic activities of Korean red ginseng (Ginseng Radix Rubra) and Crude drug-combined preparations (RGCDP-1, RGCDP-2, and RGCDP-3) were evaluated by the animal experiment. RGCDP-1 and RGCDP-2 were prepared based on Korean folk prescriptions, 'Chongmyongtang' and 'Guibitang', respectively, while RGCDP-3, by a combination of both. Among the three preparations, RGCDP-3 was found to show the most potent anti-amnestic activity as evaluated by the passive avoidance test with mice, indicating synergistic action by combined effect of RGCDP-1 and RGCDP-2.

Dual Drug-Loaded Liposomes for Synergistic Efficacy in MCF-7 Breast Cancer Cells and Cancer Stem Cells

  • Park, Hee-Bin;Kim, Yun-Ji;Lee, Seong-Min;Park, James S.;Kim, Keun-Sik
    • Biomedical Science Letters
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    • v.25 no.2
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    • pp.159-169
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    • 2019
  • Breast cancer stem cells (BCSCs) in breast cancer cells have self-renewal ability and differentiation potential. They are also resistant to drugs after chemotherapy. To overcome this resistance, we designed negatively charged 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG)-based liposomes for drug delivery. These liposomes have enhanced the therapeutic effects of a range of antitumor therapies by increasing the cellular uptake and improving drug delivery to targets sites. In this study, we investigated whether DMPG-POPC liposomes, including the neutral lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC), can specifically bind to MCF-7 breast cancer cells and increase cellular uptake compared with that by CHOL-POPC liposomes. We also estimated the cytotoxicity of DMPG-POPC liposomes encapsulated with both metformin (Met) and sodium salicylate (Sod) against breast cancer cells and BCSCs compared with that of the free drugs. Our results demonstrated that these dual drug-encapsulated liposomes significantly enhanced the cytotoxic and anti-colony formation abilities compared with individual drug-encapsulated liposomes or free drugs in BCSCs. Overall, our results suggest that DMPG-POPC liposomes containing two drugs (Met + Sod) show promise for synergistic anti-cancer therapy of breast cancer by increasing drug delivery efficiency into breast cancer cells and BCSCs.

Synergistic Anticancer Activity of 5-Aminolevulinic Acid Photodynamic Therapy in Combination with Low-dose Cisplatin on Hela Cells

  • Wei, Xiao-Qiang;Ma, Hui-Qing;Liu, Ai-Hong;Zhang, You-Zhong
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3023-3028
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    • 2013
  • Objective: Photodynamic therapy (PDT ) is a promising modality for the treatment of various tumors. In order to assist in optimizing treatment, we applied 5-ALA/PDT in combination with low-dose cisplatin to evaluate cytotoxicity in Hela cells. Methods: Antiproliferative effects of 5-ALA/PDT and cisplatin, alone and in combination, were assessed using MTT assay. To examine levels of apoptosis, Hela cells treated with 5-ALA/PDT, and combination treatment were assessed with Annexin-V/PI by flow cytometry. To investigate the molecular mechanisms underlying alterations in cell proliferation and apoptosis, Western blot analysis was conducted to determine the expression of p53, p21, Bax and Bcl-2 proteins. Results: MTT assays indicated that combination treatment obviously decreased the viability of Hela cells compared to individual drug treatment. In addition, it was confirmed that exposure of Hela cells to 5-ALA/PDT in combination with low-dose cisplatin resulted in more apoptosis in vitro. Synergistic anticancer activity was related to upregulation p53 expression and alteration in expression of p21, Bcl-2 and Bax. Conclusion: Our findings suggest that administration of 5-ALA/PDT in combination with the low-dose cisplatin may be an effective and feasible therapy for cervical cancer.

Synergistic Effect of Cisplatin and Berberine on Inhibition of Cell Growth and Induction of Apoptosis involving Oxidative Stress in HeLa Cells (자궁경부암 세포주에서 활성산소종의 영향애 의한 Apoptosis를 통하여 세포성장을 억제하는 Cisplatin과 Berberine의 상승효과)

  • Cho, Hae-Joong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.4
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    • pp.992-997
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    • 2007
  • Cisplatin is a chemotherapeutic drug which is widely used for cancer therapy including cervical cancer. The purpose of this study is to elucidate synergistic effect of Cisplatin and Berberine on the apoptosis of HeLa cells and to determine whether oxidants are formed as part of apoptotic process. Apoptotic death of HeLa cells by cisplatin and berberine was confirmed by chromatin condensation of HeLa cells and flow cytometric analysis of intracellular ROS(reactive oxygen species) production. In MTT assay, Cell viability was decreased and enhanced ROS generation in combination of cisplatin and berberine significantly, as compared with cisplatin only. Synergistic effect of Cisplatin and Berberine on the inhibition of cell growth by apoptosis was clearly observed and ROS may play an important role in apoptosis. This effect suggest the possibility lowering the concentration of chemotherapeutic drugs, which alleviate the side effect of drugs.

Combination of berberine and ciprofloxacin reduces multi-resistant Salmonella strain biofilm formation by depressing mRNA expressions of luxS, rpoE, and ompR

  • Shi, Chenxi;Li, Minmin;Muhammad, Ishfaq;Ma, Xin;Chang, Yicong;Li, Rui;Li, Changwen;He, Jingshan;Liu, Fangping
    • Journal of Veterinary Science
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    • v.19 no.6
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    • pp.808-816
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    • 2018
  • Bacterial biofilms have been demonstrated to be closely related to clinical infections and contribute to drug resistance. Berberine, which is the main component of Coptis chinensis, has been reported to have efficient antibacterial activity. This study aimed to investigate the potential effect of a combination of berberine with ciprofloxacin (CIP) to inhibit Salmonella biofilm formation and its effect on expressions of related genes (rpoE, luxS, and ompR). The fractional inhibitory concentration (FIC) index of the combination of berberine with CIP is 0.75 showing a synergistic antibacterial effect. The biofilm's adhesion rate and growth curve showed that the multi-resistant Salmonella strain had the potential to form a biofilm relative to that of strain CVCC528, and the antibiofilm effects were in a dose-dependent manner. Biofilm microstructures were rarely observed at $1/2{\times}MIC/FIC$ concentrations (MIC, minimal inhibition concentration), and the combination had a stronger antibiofilm effect than each of the antimicrobial agents used alone at $1/4{\times}FIC$ concentration. LuxS, rpoE, and ompR mRNA expressions were significantly repressed (p< 0.01) at $1/2{\times}MIC/FIC$ concentrations, and the berberine and CIP combination repressed mRNA expressions more strongly at the $1/4{\times}FIC$ concentration. The results indicate that the combination of berberine and CIP has a synergistic effect and is effective in inhibiting Salmonella biofilm formation via repression of luxS, rpoE, and ompR mRNA expressions.