Article
Chemistry, Medicinal
I-Ting Wu, Chan-Yen Kuo, Ching-Hui Su, Yu-Hsuan Lan, Chin-Chuan Hung
Summary: This study investigated the inhibitory effects of pinostrobin and tectochrysin on P-gp in MDR cancer cells and the underlying mechanisms. The results showed that these compounds were not substrates of P-gp and did not affect its expression, but they noncompetitively inhibited the efflux of rhodamine 123 and doxorubicin through P-gp, leading to the resensitization of MDR cancer cells. Therefore, pinostrobin and tectochrysin are effective P-gp inhibitors and potential candidates for resensitizing MDR cancer cells.
Article
Chemistry, Physical
Linna Liang, Wendi Huo, Bei Wang, Lingzhi Cao, Haoran Huo, Yixin Liu, Yi Jin, Xinjian Yang
Summary: Tumor multidrug resistance is a major cause of chemotherapy failure, and reversing tumor multidrug resistance is crucial for increasing the sensitivity of tumor cells to chemodrugs. The self-assembled DNAzyme nanoflowers can efficiently reverse multidrug resistance, enhance drug loading capacity, and suppress P-glycoprotein expression.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Sofija Jovanovic Stojanov, Epole N. Ntungwe, Jelena Dinic, Ana Podolski-Renic, Milica Pajovic, Patricia Rijo, Milica Pesic
Summary: Coleon U, a natural compound not recognized as a substrate of P-glycoprotein, has equal efficacy against sensitive and multidrug-resistant cancer cells. It delays the decrease in P-glycoprotein activity by decreasing mitochondrial membrane potential and inhibiting P-glycoprotein expression.
Retraction
Oncology
S. Mohana, M. Ganesan, N. Rajendra Prasad, D. Ananthakrishnan, D. Velmurugan
Summary: A correction to this paper has been published and is accessible through the original article.
Review
Biochemistry & Molecular Biology
Manuela Labbozzetta, Paola Poma, Monica Notarbartolo
Summary: Acute myeloid leukemia (AML) is difficult to treat due to the development of resistance to both traditional chemotherapy and new drugs in some patients. Multidrug resistance (MDR) in AML is often caused by the overexpression of P-glycoprotein (P-gp), which is an efflux pump. This mini-review focuses on the advantages of using natural substances as inhibitors of P-gp, including phytol, curcumin, lupeol, and heptacosane, and their mechanisms of action in AML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Yichen Tian, Yongrong Lei, Yani Wang, Jiejuan Lai, Jianhua Wang, Feng Xia
Summary: This review summarizes the mechanisms of multidrug resistance (MDR) mediated by P-glycoprotein (P-gp), including the regulation of efflux activity, the inhibition of P-gp expression, and the knockout of the ABCB1 gene. Inhibiting P-gp through screening and designing suitable compounds and techniques can overcome P-gp-mediated MDR, providing a reference for studying the reversal of P-gp-mediated MDR.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2023)
Review
Medicine, Research & Experimental
M. Ganesan, G. Kanimozhi, B. Pradhapsingh, Haseeb A. Khan, Abdullah S. Alhomida, Aishah Ekhzaimy, G. R. Brindha, N. Rajendra Prasad
Summary: The review discusses the role of natural phytochemicals in modulating ABCB1 gene expression through various signal transduction pathways in MDR cancer cells, suggesting an alternative approach to reversing MDR by downregulating P-glycoprotein expression in tumor tissues.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Agronomy
Tan Dai, Zhiwen Wang, Xingkai Cheng, Huige Gao, Li Liang, Pengfei Liu, Xili Liu
Summary: Both fungicide efflux and detoxification metabolism are involved in the resistance mechanisms of Phytophthora capsici to SYP-14288.
PEST MANAGEMENT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Eric Chekwube Aniogo, Blassan P. George, Heidi Abrahamse
Summary: The study utilized photodynamic therapy to treat MCF-7 cells overexpressed with P-glycoprotein, resulting in cell apoptosis with increased externalisation of phosphatidylserine protein and changes in apoptotic protein expression.
Article
Oncology
Chung-Pu Wu, Cheng-Yu Hung, Megumi Murakami, Yu-Shan Wu, Chun-Ling Lin, Yang-Hui Huang, Tai-Ho Hung, Jau-Song Yu, Suresh Ambudkar
Summary: In this study, we investigate the role of P-glycoprotein (P-gp) in the reduced sensitivity of cancer cells to the anaplastic lymphoma kinase (ALK) inhibitor ensartinib. Our results demonstrate that P-gp overexpression decreases the intracellular accumulation and cytotoxic activity of ensartinib in cancer cells. These findings highlight the importance of understanding the mechanisms of ensartinib resistance mediated by P-gp.
Article
Biochemistry & Molecular Biology
Yasmeen Cheema, Yusra Sajid Kiani, Kenneth J. J. Linton, Ishrat Jabeen
Summary: Researchers developed a pharmacophore model based on the cryo-EM structure of ABCB1 to screen for new inhibitors, resulting in the identification of six potential inhibitors with distinct chemistries and favorable properties. The compounds exhibited low nanomolar range inhibitory concentrations and two of them were able to resensitize ABCB1-expressing cells to taxol. This study demonstrates the utility of cryo-electron microscopy in drug identification and design.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ashutosh Singh, Sandesh Kumar Patel, Prateek Kumar, Kanhu Charan Das, Deepanshu Verma, Rohit Sharma, Timir Tripathi, Rajanish Giri, Natalia Martins, Neha Garg
Summary: The resistance of cancer cells to chemotherapy is a major challenge in drug discovery. P-glycoprotein (P-gp) overexpression is directly linked to multidrug resistance (MDR) in cancer cells. Quercetin has been reported to inhibit the activity of P-gp, but the underlying mechanism is not fully understood. This study reveals the mechanistic understanding of quercetin-induced modulation of P-gp using molecular docking and molecular dynamics simulation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Jason W. Y. Kan, Clare S. W. Yan, Iris L. K. Wong, Xiaochun Su, Zhen Liu, Tak Hang Chan, Larry M. C. Chow
Summary: Biotransformation of flavonoid dimer FD18 resulted in an active metabolite FM04, which exhibited improved druggability and was more potent in reversing P-gp-mediated PTX resistance. FM04 sensitized cancer cells to multiple anticancer drugs by inhibiting P-gp transport activity and stimulating P-gp ATPase. In addition, FM04 enhanced the intestinal absorption of PTX and showed significant antitumor activity in mouse models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Shafi Mahmud, Md. Jahirul Islam, Md. Rimon Parves, Md. Arif Khan, Lamiya Tabussum, Sinthyia Ahmed, Md. Ackas Ali, Sayo O. Fakayode, Mohammad A. Halim
Summary: This study aimed to identify potent inhibitors of P-glycoprotein using computational approaches. Two compounds showed promising anti-tumor activity with acceptable pharmacokinetic properties, and molecular docking and dynamics simulations verified their stable binding with P-glycoprotein. Principal component analysis and QSAR modeling provided insights into the interactions and predictive capabilities of the drug candidates.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Cell Biology
Chung-Pu Wu, Megumi Murakami, Yu-Shan Wu, Ya-Chen Chi, Sung-Han Hsiao, Yang-Hui Huang, Tai-Ho Hung, Suresh Ambudkar
Summary: The study explored the potential of using branebrutinib to resensitize P-gp-overexpressing multidrug-resistant cancer cells to chemotherapy by inhibiting the drug transport function of P-gp. Results showed that branebrutinib could reverse P-gp-mediated MDR at sub-toxic concentrations while maintaining cytotoxicity against drug-sensitive parental cell lines and P-gp-overexpressing multidrug-resistant variants. This new pharmacological action of branebrutinib against P-gp activity warrants further investigation in future drug combination studies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Peng Li, Yunjiao He, Teng Chen, Kit-Ying Choy, Tsun Sing Chow, Iris L. K. Wong, Xinqing Yang, Wenqin Sun, Xiaochun Su, Tak-Hang Chan, Larry M. C. Chow
Summary: Staphylococcal nuclease domain-containing protein 1 (SND1) is overexpressed in breast cancer and binds to metadherin (MTDH) to stabilize SND1, playing a crucial role in breast cancer initiation and progression. Peptide 4-2 disrupts SND1-MTDH interaction and induces SND1 degradation, potentially serving as a therapeutic option for breast cancer.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Microbiology
Chin-Fung Chan, Zhen Liu, Iris L. K. Wong, Xianliang Zhao, Zaofeng Yang, Jiale Zheng, Marianne M. Lee, Michael K. Chan, Tak Hang Chan, Larry M. C. Chow
Summary: A library of 38 novel flavonoid compounds linked with amines were synthesized, with the most promising candidate FM09h showing potent in vitro activity against parasites causing cutaneous leishmaniasis. In a mouse model, intralesional injection of FM09h demonstrated a promising effect in reducing footpad lesion thickness, comparable to sodium stibogluconate.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Review
Chemistry, Multidisciplinary
Larry M. C. Chow, Tak Hang Chan
Summary: Multidrug resistance (MDR) is a major obstacle in cancer chemotherapy, often caused by overexpression of ABC transporter proteins such as P-glycoprotein, MRP1, and BCRP on cancer cell membranes. A promising approach to overcome MDR is the use of flavonoid dimers as potent and selective inhibitors of these transporters. Flavonoid dimers have been shown to effectively inhibit the transporters without toxicity to normal cells. Further research is needed to explore the potential of these flavonoid dimers as clinical candidates for MDR reversal.
CANADIAN JOURNAL OF CHEMISTRY
(2022)
Article
Food Science & Technology
Ping Zeng, Lanhua Yi, Qipeng Cheng, Jun Liu, Sheng Chen, Kin-Fai Chan, Kwok-Yin Wong
Summary: The antimicrobial peptide zp65 shows promising potential as a food preservative due to its strong bactericidal effect and low cytotoxicity. Zp65 can easily bind to bacterial membrane and form alpha-helix structure in amphiphilic environments. The peptide has high proteolytic stability and strong binding affinity to lipopolysaccharide, suggesting its possible action target on the bacterial envelope.
INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
(2021)
Article
Food Science & Technology
Lanhua Yi, Ping Zeng, Jun Liu, Kwok-Yin Wong, Edward Wai-Chi Chan, Yanbing Lin, Kin-Fai Chan, Sheng Chen
Summary: The antimicrobial peptide zp37 showed strong bactericidal effect against E. coli O157:H7, causing cell deformation by affecting the cell membrane and binding to DNA in the cytoplasm. Experiments demonstrated low toxicity of zp37 both in vitro (HEK293 cell) and in vivo (Galleria mellonella) assays.
LWT-FOOD SCIENCE AND TECHNOLOGY
(2021)
Article
Food Science & Technology
Ping Zeng, Qipeng Cheng, Jiangtao Xu, Qi Xu, Yating Xu, Wei Gao, Kwok-Yin Wong, Kin-Fai Chan, Sheng Chen, Lanhua Yi
Summary: In this study, three novel antibacterial peptides were designed and synthesized, among which (3)K(5)K(7)G showed good antibacterial activity against drug-resistant Vibrio strains and could effectively kill Vibrio alginolyticus cells in instant jellyfish. Moreover, (3)K(5)K(7)G exhibited low cytotoxicity to mammalian cells.
Article
Biochemistry & Molecular Biology
Chantelle Tsoi, Ruixia Deng, Maxwell Kwok, Bin Yan, Carrie Lee, Hung Sing Li, Chloe Ho Yi Ma, Ruibang Luo, Kam Tong Leung, Godfrey Chi-Fung Chan, Larry Ming-cheung Chow, Ellen N. Poon
Summary: Efficient differentiation and maturation of human pluripotent stem cell-derived cardiomyocytes are essential for their application in research and therapy, and this study has shown that the differentiation schedule plays a critical role in determining both differentiation efficiency and cardiomyocyte maturation.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Materials Science, Multidisciplinary
Lin Gu, Yuanzhang Jiang, Larry M. C. Chow, Zhen Liu, Wei Gao, Yanting Han, Cong Wang, Jinlian Hu
Summary: In this study, peptide-polyurethane/urea hybrids with different peptide contents were synthesized based on the secondary structure of spider silk. These materials showed promising mechanical properties and shape memory effect, making them potential candidates for strain sensors.
MATERIALS & DESIGN
(2022)
Article
Biochemistry & Molecular Biology
Tsz Cheung Chong, Iris L. K. Wong, Jiahua Cui, Man Chun Law, Xuezhen Zhu, Xuesen Hu, Jason W. Y. Kan, Clare S. W. Yan, Tak Hang Chan, Larry M. C. Chow
Summary: This study identified Ac15(Az8)(2) as a potent and non-toxic BCRP inhibitor that can reverse BCRP-mediated drug resistance and inhibit tumor growth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ping Zeng, Qipeng Cheng, Lanhua Yi, Sharon Shui Yee Leung, Sheng Chen, Kin-Fai Chan, Kwok-Yin Wong
Summary: In this study, a small peptide library was constructed by capping a macrolactam ring at the C-terminus of a designed peptide. Eight different peptides with aspartic acid-rich macrolactam rings were found to exhibit improved antibacterial activities, and mechanistic studies revealed their mode of action.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Zhen Liu, Iris L. K. Wong, Jingcheng Sang, Fufeng Liu, Clare S. W. Yan, Jason W. Y. Kan, Tak Hang Chan, Larry M. C. Chow
Summary: We previously identified the flavonoid monomer FM04 as a potent P-glycoprotein (P-gp) inhibitor. In this study, we synthesized photoactive FM04 analogues and used LC-MS/MS to identify the FM04-binding sites on P-gp. Mutations were made around the photocrosslinked sites to validate the results. Through mutational studies, molecular docking, and molecular dynamics simulations, we found that FM04 interacts with Q1193 and I1115 in the nucleotide-binding domain 2 (NBD2) of human P-gp. It was proposed that FM04 inhibits P-gp through two novel mechanisms.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Applied
Ping Zeng, Pengfei Zhang, Lanhua Yi, Kwok-Yin Wong, Sheng Chen, Kin-Fai Chan, Sharon Shui Yee Leung
Summary: Researchers have developed a new antibacterial peptide (zp80r) by modifying the structure of a reported peptide. This peptide has shown promise in reducing the quantity of pathogenic bacteria on the surface of pork products, making it a potential candidate for controlling foodborne pathogens during storage.
Article
Biochemistry & Molecular Biology
Wenqin Sun, Iris L. K. Wong, Helen Ka-Wai Law, Xiaochun Su, Terry C. F. Chan, Gege Sun, Xinqing Yang, Xingkai Wang, Tak Hang Chan, Shengbiao Wan, Larry M. C. Chow
Summary: Tea polyphenol derivative EC31 is a potent and nontoxic P-gp inhibitor that can reverse multidrug resistance and enhance the efficacy of anticancer drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jason W. Y. Kan, Clare S. W. Yan, Iris L. K. Wong, Xiaochun Su, Zhen Liu, Tak Hang Chan, Larry M. C. Chow
Summary: Biotransformation of flavonoid dimer FD18 resulted in an active metabolite FM04, which exhibited improved druggability and was more potent in reversing P-gp-mediated PTX resistance. FM04 sensitized cancer cells to multiple anticancer drugs by inhibiting P-gp transport activity and stimulating P-gp ATPase. In addition, FM04 enhanced the intestinal absorption of PTX and showed significant antitumor activity in mouse models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)