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Your search keyword '"Qing-Zhu Fan"' showing total 2 results
Start Over Author "Qing-Zhu Fan" Topic piperlongumine
2 results on '"Qing-Zhu Fan"'

1. Piperlongumine Inhibits Akt Phosphorylation to Reverse Resistance to Cisplatin in Human Non-Small Cell Lung Cancer Cells via ROS Regulation

Author

Chao Zhang, Lian-Jun He, Yi-Bao Zhu, Qing-Zhu Fan, Dong-Dong Miao, Sheng-Peng Zhang, Wen-Ying Zhao, and Xiao-Ping Liu

Subjects
Akt, multidrug resistance, piperlongumine, NSCLC, apoptosis, Therapeutics. Pharmacology, RM1-950
Abstract

Resistance is a major concern when administering chemotherapy to patients with non-small cell lung cancer (NSCLC). Chemosensitizer are agents that can reverse resistance to chemotherapeutic drugs, thereby enhancing the chemosensitivity of tumor cells. Thus, their development will improve therapeutic efficacy in cancer. However, few effective chemosensitizer have been identified to date. Piperlongumine (PL) has been shown to effectively reverse resistance to chemotherapeutic drugs in several types of cancers. However, the mechanisms associated with the chemotherapy resistance reversal effect of PL and its regulation of target factors in chemotherapy resistance cells are still unclear. This study investigated the reversal effect of PL both in vitro and in vivo, and provided evidence that PL inhibited the phosphorylation of Akt via the accumulation of reactive oxygen species in chemotherapy resistance cells. Consequently, various Akt activation-dependent genes caused a reduction of drug efflux and induction of apoptosis in cisplatin-resistant A549 NSCLC cells. Our results indicate that Akt phosphorylation may play a functional role in the reversal effect of PL and contribute, at least in part, to the treatment outcomes of patients with chemotherapy resistance.

Published
2019
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2. Design, synthesis, and biological evaluation of a novel indoleamine 2,3-dioxigenase 1 (IDO1) and thioredoxin reductase (TrxR) dual inhibitor

Author

Sheng-Peng Zhang, Yi-Bao Zhu, Chao Zhang, Lian-Jun He, Xiao-Ping Liu, Dong-Dong Miao, Ji Zhou, and Qing-Zhu Fan

Subjects
Thioredoxin Reductase 1, medicine.medical_treatment, Thioredoxin reductase, Antineoplastic Agents, Apoptosis, 01 natural sciences, Biochemistry, chemistry.chemical_compound, Structure-Activity Relationship, Cancer immunotherapy, Drug Discovery, medicine, Tumor Cells, Cultured, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase, Enzyme Inhibitors, Molecular Biology, Piperlongumine, Cell Proliferation, chemistry.chemical_classification, Gene knockdown, Reactive oxygen species, Dose-Response Relationship, Drug, Molecular Structure, 010405 organic chemistry, Organic Chemistry, Dioxolanes, Immunotherapy, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, chemistry, Drug Design, Cancer cell, Cancer research, Drug Screening Assays, Antitumor, Reactive Oxygen Species
Abstract

Targeting the Trp-Kyn pathway is an attractive approach for cancer immunotherapy. Thioredoxin reductase (TrxR) enzymes are reactive oxygen species (ROS) modulators that are involved in the tumor cell growth and survival processes. The 4-phenylimidazole scaffold is well-established as useful for indoleamine 2,3-dioxygenase 1 (IDO1) inhibition, while piperlongumine (PL) and its derivatives have been reported to be inhibitors of TrxR. To take advantage of both immunotherapy and TrxR inhibition, we designed a first-generation dual IDO1 and TrxR inhibitor (ZC0101) using the structural combination of 4-phenylimidazole and PL scaffolds. ZC0101 exhibited better dual inhibition against IDO1 and TrxR in vitro and in cell enzyme assays than the uncombined forms of 4-phenylimidazole and PL. It also showed antiproliferative activity in various cancer cell lines, and a selective killing effect between normal and cancer cells. Furthermore, ZC0101 effectively induced apoptosis and ROS accumulation in cancer cells. Knockdown of TrxR1 and IDO1 expression induced cellular enzyme inhibition and ROS accumulation effects during ZC0101 treatment, but only reduced TrxR1 expression was able to improve ZC0101's antiproliferation effect. This proof-of-concept study provides a novel strategy for cancer treatment. ZC0101 represents a promising lead compound for the development of novel antitumor agents that can also be used as a valuable probe to clarify the relationships and mechanisms of cancer immunotherapy and ROS modulators.

Published
2020

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