Search results for "BCG"
showing 10 items of 65 documents
Repurposing of Bromocriptine for Cancer Therapy
2018
Bromocriptine is an ergot alkaloid and dopamine D2 receptor agonist used to treat Parkinson’s disease, acromegaly, hyperprolactinemia, and galactorrhea, and more recently diabetes mellitus. The drug is also active against pituitary hormone-dependent tumors (prolactinomas and growth-hormone producing adenomas). We investigated, whether bromocriptine also inhibits hormone-independent and multidrug-resistant (MDR) tumors. We found that bromocriptine was cytotoxic towards drug-sensitive CCRF-CEM, multidrug-resistant CEM/ADR5000 leukemic cells as well as wild-type or multidrug-resistant ABCB5-transfected HEK293 cell lines, but not sensitive or BCRP-transfected multidrug-resistant MDA-MB-231 brea…
Molecular Determinants of Sensitivity or Resistance of Cancer Cells Toward Sanguinarine.
2018
For decades, natural products represented a significant source of diverse and unique bioactive lead compounds in drug discovery field. In Clinical oncology, complete tumors remission is hampered by the development of drug-resistance. Therefore, development of cytotoxic agents that may overcome drug resistance is urgently needed. Here, the natural benzophenanthridine alkaloid sanguinarine has been studied for its cytotoxic activity against multidrug resistance (MDR) cancer cells. We investigated the role of the ATP-binding cassette (ABC) transporters BCRP/ABCG2, P-glycoprotein/ABCB1 and its close relative ABCB5 in drug resistance. Further drug resistance mechanisms analyzed in this study wer…
Reversal of multidrug resistance by Marsdenia tenacissima and its main active ingredients polyoxypregnanes.
2016
Abstract Ethnopharmacological relevance Multidrug resistance (MDR) of cancer is often associated with the overexpression of ATP-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp), multidrug resistance-associated protein-1 (MRP-1) and breast cancer resistance protein (BCRP or ABCG2), in cancer cells, which facilitates the active efflux of a wide variety of chemotherapeutic drugs out of the cells. Marsdenia tenacissima is a traditional Chinese medicinal herb that has long been clinically used for treatment of cancers, particularly in combinational use with anticancer drugs. Polyoxypregnanes (POPs) are identified as main constituents of this herb, and three of them have been re…
Harnessing Unconventional T Cells for Immunotherapy of Tuberculosis
2020
Even if the incidence of tuberculosis (TB) has been decreasing over the last years, the number of patients with TB is increasing worldwide. The emergence of multidrug-resistant and extensively drug-resistant TB is making control of TB more difficult. Mycobacterium bovis bacillus Calmette–Guérin vaccine fails to prevent pulmonary TB in adults, and there is an urgent need for a vaccine that is also effective in patients with human immunodeficiency virus (HIV) coinfection. Therefore, TB control may benefit on novel therapeutic options beyond antimicrobial treatment. Host-directed immunotherapies could offer therapeutic strategies for patients with drug-resistant TB or with HIV and TB coinfecti…
Liver X Receptor–Mediated Induction of Cholesteryl Ester Transfer Protein Expression Is Selectively Impaired in Inflammatory Macrophages
2009
Objective— Cholesteryl ester transfer protein (CETP) is a target gene for the liver X receptor (LXR). The aim of this study was to further explore this regulation in the monocyte-macrophage lineage and its modulation by lipid loading and inflammation, which are key steps in the process of atherogenesis. Methods and Results— Exposure of bone marrow–derived macrophages from human CETP transgenic mice to the T0901317 LXR agonist increased CETP, PLTP, and ABCA1 mRNA levels. T0901317 also markedly increased CETP mRNA levels and CETP production in human differentiated macrophages, whereas it had no effect on CETP expression in human peripheral blood monocytes. In inflammatory mouse and human mac…
Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy in vitro and in vivo
2021
Multidrug resistance (MDR) mediated by ATP binding cassette subfamily B member 1 (ABCB1) is significantly hindering effective cancer chemotherapy. However, currently, no ABCB1-inhibitory drugs have been approved to treat MDR cancer clinically, mainly due to the inhibitor specificity, toxicity, and drug interactions. Here, we reported that three polyoxypregnanes (POPs) as the most abundant constituents of Marsdenia tenacissima (M. tenacissima) were novel ABCB1-modulatory pro-drugs, which underwent intestinal microbiota-mediated biotransformation in vivo to generate active metabolites. The metabolites at non-toxic concentrations restored chemosensitivity in ABCB1-overexpressing cancer cells v…
Strategies to gain novel Alzheimer’s disease diagnostics and therapeutics using modulators of ABCA transporters
2021
Adenosine-triphosphate-(ATP)-binding cassette (ABC) transport proteins are ubiquitously present membrane-bound efflux pumps that distribute endo- and xenobiotics across intra- and intercellular barriers. Discovered over 40 years ago, ABC transporters have been identified as key players in various human diseases, such as multidrug-resistant cancer and atherosclerosis, but also neurodegenerative diseases, such as Alzheimer���s disease (AD). Most prominent and well-studied are ABCB1, ABCC1, and ABCG2, not only due to their contribution to the multidrug resistance (MDR) phenotype in cancer, but also due to their contribution to AD. However, our understanding of other ABC transporters is limited…
Isopetasin and S-isopetasin as novel P-glycoprotein inhibitors against multidrug-resistant cancer cells
2019
Abstract Background A major problem of cancer treatment is the development of multidrug resistance (MDR) to chemotherapy. MDR is caused by different mechanisms such as the expression of the ABC-transporters P-glycoprotein (P-gp, MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2). These transporters efflux xenobiotic toxins, including chemotherapeutics, and they were found to be overexpressed in different cancer types. Purpose Identification of novel molecules that overcome MDR by targeting ABC-transporters. Methods Resazurin reduction assay was used for cytotoxicity test. AutoDock 4.2. was used for molecular docking. The function of P-gp and BCRP was tested using a doxorubicin …
Collateral sensitivity of drug-resistant ABCB5- and mutation-activated EGFR overexpressing cells towards resveratrol due to modulation of SIRT1 expre…
2019
Abstract Background In the drug discovery field, natural products deemed a precious source of novel lead compounds. They have the ability to bypass or overcome multidrug resistance (MDR) in cancer cells. Purpose In this study, the natural polyphenolic stilbene resveratrol (RES) has been studied for its cytotoxic activity toward MDR cancer cells. Methods Resazurin assay was used to investigate the cytotoxicity of RES not only against a panel of drug-resistant cancer cells overexpressing P-glycoprotein/ABCB1, BCRP/ABCG2, ABCB5 (ATP-binding cassette transporters), but also mutation-activated EGFR. The assessment of proteins expression was done by Western blot analysis. COMPARE and hierarchical…
Inhibition of ATP-Binding Cassette Transporters by Chinese Herbs and Phytochemicals
2012
The gene family of ATP-binding cassette (ABC) transporters is widely distributed over the evolutionary tree of life from bacteria to man. In cancer, several ABC transporters are involved in the transport of anticancer drugs. This leads to the development of resistance to a broad spectrum of anticancer agents, termed multidrug resistance. An attractive strategy to overcome multidrug resistance is to block the transport function of ABC transporters leading to lethal intracellular concentrations of anticancer drugs. Efforts to identify transport inhibitors lead to a huge amount of chemical substances, none of which successfully passed clinical trials in cancer patients because of high toxicity…