Article
Chemistry, Medicinal
Laura Braconi, Silvia Dei, Marialessandra Contino, Chiara Riganti, Gianluca Bartolucci, Dina Manetti, Maria Novella Romanelli, Maria Grazia Perrone, Nicola Antonio Colabufo, Stefano Guglielmo, Elisabetta Teodori
Summary: New 2,5- and 1,5-disubstituted tetrazoles, and 2,5-disubstituted-1,3,4-oxadiazoles were synthesized and studied as MDR reversers, showing potent inhibitory effects on P-gp transport activity and increasing the antiproliferative effect of doxorubicin in MDR cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Harlan L. Pietz, Ata Abbas, Zachary Lee Johnson, Michael L. Oldham, Hiroaki Suga, Jue Chen
Summary: This study identifies a macrocyclic peptide CPI1 that inhibits the function of MRP1 and blocks substrate transport. The findings suggest that CPI1 could be a potential therapeutic candidate.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Chao-Yun Cai, Qiu-Xu Teng, Megumi Murakami, Suresh V. Ambudkar, Zhe-Sheng Chen, Vijaya L. Korlipara
Summary: A series of 22 quinazolinamine derivatives with potent inhibitory activities on BCRP and P-gp were synthesized. Compound 22 was identified as a dual BCRP and P-gp inhibitor, while compound 33 showed BCRP inhibitory activity. These compounds changed the localization of BCRP and P-gp, inhibiting the efflux of anticancer drugs by the two ABC transporters. Compounds 22 and 33 also stimulated ATP hydrolysis, increasing the accumulation of mitoxantrone in BCRP-overexpressing cells.
Review
Pharmacology & Pharmacy
Manasi S. Pote, Rajesh N. Gacche
Summary: This review provides updated information on the structure, function, and regulatory mechanisms of major multidrug resistance (MDR) related ATP binding cassette (ABC) transporters, which play a significant role in limiting the efficacy of anticancer drugs. The effects of modulators on the functions of ABC transporters such as P-glycoprotein, MRP1, and BCRP are discussed. Additionally, the potential use of these ABC transporter modulators in clinical practice to alleviate the emerging MDR crisis in cancer treatment is highlighted.
DRUG DISCOVERY TODAY
(2023)
Article
Pharmacology & Pharmacy
Lei Zhang, Biwei Ye, Yunfeng Lin, Yi-Dong Li, Jing-Quan Wang, Zhuo Chen, Feng-Feng Ping, Zhe-Sheng Chen
Summary: In this study, the researchers investigated the effect of the CDK4/6 inhibitor, ribociclib, on multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) in human epidermoid carcinoma cells. They found that ribociclib increased the efficacy of a P-gp substrate drug, colchicine, by down-regulating the expression of P-gp and increasing its ATPase activity. Docking studies suggested that ribociclib interacted with the drug-substrate binding site of P-gp. Additionally, ribociclib inhibited the drug efflux activity of P-gp, leading to increased intracellular accumulation of doxorubicin. These findings suggest that ribociclib may be a potential agent for combined therapy in cancers with P-gp-mediated MDR.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Liadys Mora Lagares, Yunierkis Perez-Castillo, Nikola Minovski, Marjana Novic
Summary: P-gp is an important protein involved in drug efflux and multidrug resistance. Molecular dynamics simulations can provide valuable insights into the binding behavior and conformational changes of P-gp in the presence of different compounds.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Peter Szatmari, Eszter Ducza
Summary: ABC transporters are essential for drug efflux in the human body, with significant impact on pharmacokinetics and pharmacologic properties of drugs. P-gp and BCRP transporters, in particular, play a crucial role in barrier tissues. During pregnancy, placental and intestinal ABC transporters are of great importance for drug absorption and distribution. Their expression changes with gestational age and can affect the efficacy of various therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Danijela Mandic, Lana Nezic, Ljiljana Amdzic, Natasa Vojinovic, Radoslav Gajanin, Miroslav Popovic, Jugoslav Deri, Milena Todorovic Balint, Jelena Dumanovic, Zoran Milovanovic, Jelica Grujic-Milanovic, Ranko Skrbic, Vesna Jacevic
Summary: This study aimed to investigate whether the coexpression of ABC transporters and survivin was associated with the response to R-CHOP treatment in DLBCL patients. The results showed that DLBCL might harbor molecular signatures such as MRP1/ABCC1, survivin, and BCRP/ABCC2 overexpression that can predict resistance to R-CHOP.
Review
Biochemistry & Molecular Biology
Ji He, Erika Fortunati, Dong-Xu Liu, Yan Li
Summary: Chemotherapeutics are a main therapy for metastatic breast cancers, but multidrug resistance due to ABC transporters remains a challenge. Targeting ABCB1 to reverse drug resistance in clinical trials has been disappointing, but ABC transporters may play roles in breast cancer development and metastasis beyond efflux function. Understanding the functions and regulations of ABC transporters in breast cancer biology may lead to more targeted and novel therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Chemistry, Medicinal
Hang Zhang, Haiwei Xu, Charles R. Ashby, Yehuda G. Assaraf, Zhe-Sheng Chen, Hong-Min Liu
Summary: This review highlights the recent achievements in drug design and mechanism studies of newly synthetic P-gp inhibitors in the past 5 years, which will help overcome multidrug resistance in cancer chemotherapy.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Lei Zhang, Yidong Li, Chaohua Hu, Yangmin Chen, Zhuo Chen, Zhe-Sheng Chen, Jian-Ye Zhang, Shuo Fang
Summary: This study reveals CDK6-PI3K as a novel target signaling axis to reverse ABCB1-mediated multidrug resistance for the first time in cancers. Deficiency of CDK6 leads to downregulation of ABCB1 expression and reversal of multidrug resistance.
Article
Biology
Absarul Haque, Ghazanfar Ali Baig, Abdulelah Saleh Alshawli, Khalid Hussain Wali Sait, Bilal Bin Hafeez, Manish Kumar Tripathi, Badrah Saeed Alghamdi, Hani S. H. Mohammed Ali, Mahmood Rasool
Summary: This study determined the binding affinity and potential interaction sites of the multidrug resistance protein 1 (MRP1) with various anticancer drugs using homology modelling and molecular docking analysis. The results suggested that Carboplatin could be an appropriate therapeutic choice against MRP1 in ovarian cancer, and combining Carboplatin with Gemcitabine may overcome multidrug resistance phenotype.
Article
Pharmacology & Pharmacy
Sai-Qi Wang, Qiu-Xu Teng, Shuai Wang, Zi-Ning Lei, Hui-Hui Hu, Hui-Fang Lv, Bei-Bei Chen, Jian-Zheng Wang, Xiao-Jing Shi, Wei-Feng Xu, Hong-Min Liu, Xiao-Bing Chen, Zhe-Sheng Chen, Bin Yu
Summary: The compound WS-716 based on triazolo[1,5-a]pyrimidine was reported as a highly potent, specific, and orally active P-gp inhibitor against MDR cancer, showing therapeutic promise. WS-716 and PTX synergistically inhibited growth of resistant cells, induced apoptosis, and increased sensitivity of MDR tumors to PTX.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Biochemistry & Molecular Biology
Kamila Siedlecka-Kroplewska, Agata Wronska, Zbigniew Kmiec
Summary: Acute myeloid leukemia is characterized by uncontrolled proliferation of abnormal myeloid progenitor cells. Despite recent advances in treatment, prognosis remains poor, driving the search for new chemotherapeutics. Piceatannol shows promise as a chemotherapeutic agent for leukemia, but its use may be associated with the risk of multidrug resistance, suggesting the need for combination therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Yan-Ni Bao, Xiu-Li Xie, Li-Li Lu, Wen-Hao Liu, Yu-Chen Ma, Yi-Jun Ke, Huan Ren, Li-Na Tan, Li-Fang Wu, Jue Song, Yong Jin, Xiao-Yan Liu
Summary: Multidrug resistance (MDR) is a major obstacle in cancer treatment. In this study, layered double hydroxide nanoparticles (LDH) were used to co-deliver DOX and siRNA targeting BCRP RNA to reverse drug resistance in MCF-7/ADR cells, and enhance the anticancer activity of DOX. The results showed that siRNA-DOX@NiFe-LDH effectively silenced the BCRP gene and inhibited cell proliferation in vitro, and also demonstrated a significant antitumor effect in vivo.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2023)
Article
Medicine, Research & Experimental
Anna Palko-Labuz, Kamila Sroda-Pomianek, Olga Wesolowska, Edyta Kostrzewa-Suslow, Anna Uryga, Krystyna Michalak
BIOMEDICINE & PHARMACOTHERAPY
(2019)
Article
Oncology
Kamila Sroda-Pomianek, Krystyna Michalak, Anna Palko-Labuz, Anna Uryga, Berenika Szczesniak-Siega, Olga Wesolowska
ANTICANCER RESEARCH
(2019)
Article
Biochemistry & Molecular Biology
Kamila Sroda-Pomianek, Krystyna Michalak, Anna Palko-Labuz, Anna Uryga, Piotr Swiatek, Michal Majkowski, Olga Wesolowska
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Pharmacology & Pharmacy
Kamila Sroda-Pomianek, Krystyna Michalak, Anna Palko-Labuz, Andrzej Pola, Piotr Dziegiel, Bartosz Pula, Piotr Swiatek, Olga Wesolowska
EUROPEAN JOURNAL OF PHARMACOLOGY
(2019)
Review
Oncology
Andrzej Teisseyre, Anna Palko-Labuz, Kamila Sroda-Pomianek, Krystyna Michalak
FRONTIERS IN ONCOLOGY
(2019)
Article
Toxicology
A. Palko-Labuz, E. Kostrzewa-Suslow, T. Janeczko, K. Sroda-Pomianek, A. Pola, A. Uryga, K. Michalak
HUMAN & EXPERIMENTAL TOXICOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Olga Wesolowska, Krystyna Michalak, Maria Blaszczyk, Joseph Molnar, Kamila Sroda-Pomianek
Article
Biochemistry & Molecular Biology
Kamila Sroda-Pomianek, Anna Palko-Labuz, Andrzej Pola, Miroslawa Ferens-Sieczkowska, Olga Wesolowska, Agata Koziol
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Chemistry, Physical
Andrzej Teisseyre, Anna Uryga, Krystyna Michalak
Summary: Voltage-gated potassium channels of the Kv1.3 type are considered as potential new molecular targets in several pathologies, including cancer disorders. Lipophilic nontoxic organic inhibitors of Kv1.3 channels may have clinical applications in supporting therapy for cancer diseases. Statins, small-molecule organic compounds widely used in hypercholesterolemia and atherosclerosis treatment, are effective inhibitors of Kv1.3 channels in human T cell line Jurkat, showing potential for cancer treatment.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Biochemistry & Molecular Biology
Anna Palko-Labuz, Anna Gliszczynska, Magdalena Skonieczna, Andrzej Pola, Olga Wesolowska, Kamila Sroda-Pomianek
Summary: The study found that conjugates of anisic and veratric acid with phosphatidylcholine could enhance their anticancer effects and selectively target melanoma cells, while also increasing their antioxidant activity. Conjugates substituted by phenolic acid at both the sn-1 and sn-2 positions of phosphatidylcholine appeared to be the most promising.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Anna Palko-Labuz, Maria Blaszczyk, Kamila Sroda-Pomianek, Olga Wesolowska
Summary: Isobavachalcone (IBC) is an active substance from the medicinal plant Psoralea corylifolia with antioxidative, anti-inflammatory, antibacterial, and anticancer activities. Studies have shown that IBC can benefit MDR cancer cells by interfering with the lipid phase of cellular membrane and ABCB1 transporter.
Article
Oncology
Anna Palko-Labuz, Jerzy Maksymowicz, Beata Sobieszczanska, Agnieszka Wikiera, Magdalena Skonieczna, Olga Wesolowska, Kamila Sroda-Pomianek
Summary: Colorectal cancer (CRC) is the second leading cause of cancer mortality globally. Irinotecan, commonly used in CRC treatment, can be metabolized by colonic bacteria back to its active form, leading to severe side effects. This study found that novel apple pectin (PC) enhanced the anticancer effects of irinotecan while reducing bacterial enzyme activity that causes side effects, making PC a promising adjunct to irinotecan therapy.
Article
Chemistry, Medicinal
Jerzy Maksymowicz, Anna Palko-Labuz, Beata Sobieszczanska, Mateusz Chmielarz, Miroslawa Ferens-Sieczkowska, Magdalena Skonieczna, Agnieszka Wikiera, Olga Wesolowska, Kamila Sroda-Pomianek
Summary: This study investigated the anti-cancer and anti-inflammatory activities of two modified pectins isolated from apple pomace. The pectins exhibited anti-cancer effects by reducing cell viability, inducing apoptosis, and increasing reactive oxygen species. They also showed synergy with SN-38, a common component of colon cancer treatment. Furthermore, the pectins demonstrated significant anti-inflammatory activity and their interaction with galectin-3 and TLR4 was suggested to be responsible for their effects.
