Article
Chemistry, Medicinal
Nathupakorn Dechsupa, Nopawit Khamto, Pornthip Chawapun, Sadanon Siriphong, Phattarawadee Innuan, Authaphinya Suwan, Thitiworada Luangsuep, Nichakorn Photilimthana, Witchayaporn Maita, Rossarin Thanacharttanatchaya, Padchanee Sangthong, Puttinan Meepowpan, Chatchanok Udomtanakunchai, Jiraporn Kantapan
Summary: This paper explores the efficacy of pentagalloyl glucose (PGG) in reversing multidrug resistance in drug-resistant leukemic cells. The results indicate that PGG selectively induces cytotoxicity and enhances sensitivity to anticancer drugs in these cells. PGG reduces the expression of P-gp and inhibits P-gp-mediated efflux, leading to increased intracellular drug accumulation. Molecular dynamics simulation suggests that PGG binds tightly to both the substrate and ATP binding sites of P-gp.
Article
Pharmacology & Pharmacy
Xincheng Zhong, Xiaoyan Bao, Haiqing Zhong, Yi Zhou, Zhentao Zhang, Yiying Lu, Qi Dai, Qiyao Yang, Peng Ke, Yiyi Xia, Linjie Wu, Zaiyun Sui, Yan Lu, Min Han, WenHong Xu, Jianqing Gao
Summary: In this study, TPP-DOX@MnBSA nanoparticles were prepared by co-loading TPP-DOX and manganese using bovine serum albumin as a carrier. These nanoparticles exhibited a combined effect of chemotherapy and chemodynamic therapy, effectively inhibiting the growth of both sensitive and drug-resistant tumor cells, and potentially reducing tumor stemness and metastasis.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Chemistry, Multidisciplinary
Jelena Vasiljeva, Marina Makrecka-Kuka, Ilona Domracheva, Karlis Vilks, Pavels Dimitrijevs, Pavel Arsenyan
Summary: This study reports the design and synthesis of novel selenophenoquinolinones and their ability to reverse doxorubicin resistance in uterus sarcoma cells. Compound 5e demonstrated the best cytotoxicity and attenuated cell resistance to doxorubicin by inhibiting ABCB1 transporter activity and suppressing ABCB1 gene expression.
NEW JOURNAL OF CHEMISTRY
(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.
Article
Chemistry, Medicinal
Qianqian Qiu, Feng Zou, Huilan Li, Wei Shi, Daoguang Zhou, Ping Zhang, Teng Li, Ziyu Yin, Zilong Cai, Yuxuan Jiang, Wenlong Huang, Hai Qian
Summary: Compound 21 is a dual inhibitor that can block both P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), showing potential in overcoming multidrug resistance and improving the oral bioavailability of specific drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Sijongesonke Peter, Sibusiso Alven, Rejoice Bethusile Maseko, Blessing Atim Aderibigbe
Summary: The scarcity of effective cancer therapeutics is a pressing issue. Doxorubicin, currently used in cancer treatment, is limited by drug resistance and toxicity. Combination with other chemotherapeutic agents is considered an effective treatment option.
Article
Pharmacology & Pharmacy
Chih-Peng Lin, Shu-Hui Wu, Tzu-Yin Lin, Chia-Hui Chu, Leu-Wei Lo, Ching-Chuan Kuo, Jang-Yang Chang, Szu-Chun Hsu, Bor-Sheng Ko, Ming Yao, Jong-Kai Hsiao, Shih-Wei Wang, Dong-Ming Huang
Summary: This study develops a simple and versatile biological drug delivery system (bDDS) based on human red blood cell-derived vesicles (RDVs), which shows excellent biocompatibility for cancer chemotherapy. The bDDS, named Dox-gluRDVs, effectively suppress multidrug resistance in uterine sarcoma by inducing cell death through a lysosomal-mitochondrial axis-dependent mechanism.
PHARMACOLOGICAL RESEARCH
(2023)
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
Oncology
Isabella Giacomini, Margherita Cortini, Mattia Tinazzi, Nicola Baldini, Veronica Cocetta, Eugenio Ragazzi, Sofia Avnet, Monica Montopoli
Summary: Osteosarcoma, the most common bone tumor in children and young adults, is also the second most fatal cancer. Despite the clinical benefit of chemotherapy, patients with osteosarcoma still face a poor prognosis due to drug resistance and frequent growth and metastasis of the disease. This study reveals a different mitochondrial phenotype in doxorubicin-resistant cancer cells and suggests targeting the altered pathway to reverse drug resistance. These findings contribute to understanding mitochondrial metabolism changes and developing strategies to overcome doxorubicin resistance in osteosarcoma.
Review
Genetics & Heredity
Samantha W. Jones, Amy L. Ball, Amy E. Chadwick, Ana Alfirevic
Summary: The triad of drug efficacy, toxicity and resistance is crucial in determining the risk-benefit balance of therapeutics. Pharmacogenomics can potentially improve this balance by stratifying patient populations based on DNA variants. Research on the impact of mitochondrial DNA variation on drug response is still inconclusive and further studies are needed to explain the variability in drug response.
FRONTIERS IN GENETICS
(2021)
Article
Pharmacology & Pharmacy
Gamal Eldein Fathy Abd-ellatef, Elena Gazzano, Ahmed H. El-Desoky, Ahmed R. Hamed, Joanna Kopecka, Dimas Carolina Belisario, Costanzo Costamagna, Mohamed Assem S. Marie, Sohair R. Fahmy, Abdel-Hamid Z. Abdel-Hamid, Chiara Riganti
Summary: The study demonstrated that Glabratephrin (Glab), a prenylated flavonoid from Tephrosia purpurea, can increase doxorubicin accumulation and cytotoxicity in triple negative breast cancer cells with high levels of Pgp. Glab also reduces the growth of Pgp-expressing tumors without adding significant extra-toxicities to doxorubicin treatment.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Mohamed A. Morsy, Mahmoud Kandeel, Ahmed R. N. Ibrahim, Seham A. Abdel-Gaber, Shery Jacob, Katharigatta N. Venugopala, Pottathil Shinu, Mahmoud El-Daly
Summary: Carnosine was found to be a potential inhibitor of P-gp activity and potentiate doxorubicin-induced cytotoxicity, providing a potential beneficial role in the treatment of multidrug-resistant cancers.
Article
Chemistry, Medicinal
Saghar Mozaffari, David Salehi, Parvin Mahdipoor, Richard Beuttler, Rakesh Tiwari, Hamidreza Montazeri Aliabadi, Keykavous Parang
Summary: The hybrid cyclic-linear [R5K]W(7)A-Dox conjugate showed significant efficacy in inhibiting cancer cell proliferation with minimal toxicity to normal cells, compared to free Dox. It also exhibited higher efficiency in Dox-resistant cells when compared to free Dox.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Sri Nitya Reddy Induri, Payalben Kansara, Scott C. Thomas, Fangxi Xu, Deepak Saxena, Xin Li
Summary: Metformin is widely used for treating type 2 diabetes and may promote healthy aging. The gut microbiome could play a role in the efficacy of metformin as its concentration is higher in the gut. Understanding the mechanisms of metformin in promoting a healthy gut microbiome and aging requires a systems-level approach.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Jessica Chu, Erika Panfen, Linna Wang, Anthony Marino, Xue-Qing Chen, R. Marcus Fancher, Raviraj Landage, Omprakash Patil, Salil Dileep Desai, Devang Shah, Yongjun Xue, Michael Sinz, Hong Shen
Summary: The aim of this study was to evaluate the differences between intestinal and systemic P-gp and BCRP in drug disposition. The results showed that ECD is a potent inhibitor of intestinal P-gp and BCRP. The inhibition potential of ECD towards human and animal P-gp and BCRP was assessed in vitro and in vivo.
PHARMACEUTICAL RESEARCH
(2023)