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Garcinia indica (Kokum) and Ilex aquifolium (European Holly)
Published in Azamal Husen, Herbs, Shrubs, and Trees of Potential Medicinal Benefits, 2022
Dicson Sheeja Malar, Mani Iyer Prasanth, Tewin Tencomnao, James Michael Brimson, Anchalee Prasansuklab
Connectivity map approach indicates that UA exhibit inhibitory effect against breast cancer cells by modulating some of the key pathways including PLK1, IKK/NF-κB, and RAF/ERK pathways (Guo et al., 2020). In addition, downregulation of Nrf-2, PI3K/AKT, JNK pathway were also reported (Zhang et al., 2020; Luo et al., 2017; Yeh et al., 2010). UA sensitized the triple negative breast cancer cells to doxorubicin and enhances apoptosis by targeting ZEB1-AS1/miR-186-5p/ABCC1 axis (Lu et al., 2021). ATP-binding cassette transporter C (ABCC1) are transporters that mediates the efflux of drugs from cancer cells, preventing their accumulation and causing chemoresistance. UA inhibits the growth of breast cancer stem-like cells by attenuating sFRP4 mediated Wnt/β-catenin pathway and suppressing miRNA-499a-5p involved in invasion and metastasis (Mandal et al., 2021).
Targeted Therapy for Cancer Stem Cells
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Rama Krishna Nimmakayala, Saswati Karmakar, Garima Kaushik, Sanchita Rauth, Srikanth Barkeer, Saravanakumar Marimuthu, Moorthy P. Ponnusamy
The canonical Wnt/β-catenin signaling pathway is crucial for the regulation of normal development and stem cell maintenance, and studies show that mutations in these pathway molecules could make this pathway constitutively active leading to the drug resistance and uncontrolled proliferation of CSCs in various cancers [15]. Another drug resistance signaling mechanism, Hh signaling is required for normal embryonic development and tissue homeostasis. However, the pathway also regulates drug resistance genes in various cancers. For example, the Hh signaling transcription factor, Gli2 increases the expression of ABCC1 drug-resistant transporter leading to increased therapy resistance in hepatoma cells [16]. Moreover, aberrant activation of Notch signaling, which is required for normal development and tissue homeostasis, increases the expression levels of major CSC genes such as Myc, Nanog, OCT-4 and Sox2 [17]. EGFR mediated signaling is also known to regulate drug resistance in CSCs. Studies report that EGFR signaling is constitutively active in CSCs, and the inhibition of the signaling sensitizes glioma stem cells to radiation mediated cytotoxicity [18]. Also, OCT-4, a pluripotent transcription factor, regulates the genes of ABC transporters, especially ABCG2 drug resistant protein [19]. Myc driven signaling also induces ABC transporter genes such as ABCC1 [20].
Lung transporters and absorption mechanisms in the lungs
Published in Anthony J. Hickey, Heidi M. Mansour, Inhalation Aerosols, 2019
Mohammed Ali Selo, Hassan H.A. Al-Alak, Carsten Ehrhardt
Apart from MRP1 (ABCC1), which is the best studied member of the subfamily in terms of activity and drug transport in the lung, few data on the pulmonary function of other MRP are available (25). The pulmonary activity of MRP1 has been determined by positron emission tomography (PET) imaging technique in vivo in mice (54).
Overcoming multidrug resistance through targeting ABC transporters: lessons for drug discovery
Published in Expert Opinion on Drug Discovery, 2022
Mohammad Feyzizadeh, Ashkan Barfar, Zeinab Nouri, Muhammad Sarfraz, Parvin Zakeri-Milani, Hadi Valizadeh
Multidrug resistance-associated protein 1 (MRP1) is a 190-kDa phosphoglycoprotein that in humans is encoded by the ABCC1 gene. Structure studies showed that it consists of three TMDs and two NBDs. They are set as TMD0-TMD1-NBD1-TMD2-NBD2 [18,32]. ABCC1 is expressed in several organs and tissues such as the kidney, intestine, BBB, lung, testis, and peripheral blood mononuclear cells; it was first detected in a mutant lung cancer cell line showing resistance to specific anticancer drugs. It is involved in the cellular export of physiological compounds and transports a variety of xenobiotics [18]. In Alzheimer’s patients, amyloid-β (Aβ) accumulation in the brain is critical; deficiency of ABCC1 could increase cerebral Aβ level [18,33]. In addition, ABCC1 has a role in the MDR of tumor cells because it could transport many anticancer drugs to the extracellular environment. The ABCC1 transporter is particularly prevalent in neuroblastoma, lung, breast, and prostate tumors and could interfere with treatment [34]. ABCC1 substrates are mostly amphipathic. They are frequently organic anions conjugated to glutathione conjugates (e.g. doxorubicin and cyclophosphamide), sulfate conjugates, and others such as folic acid, arsenite, and ritonavir. It is noteworthy that different types of efflux pumps may select their substrate from different cell locations so that P-gp substrates are predominantly hydrophobic and could transport substrates from the lipid bilayer, but MRP1 probably gets them from the cytosol [18].
Targeted drug therapy in nonsmall cell lung cancer: clinical significance and possible solutions-part II (role of nanocarriers)
Published in Expert Opinion on Drug Delivery, 2021
Khushwant S. Yadav, Archana Upadhya, Ambikanandan Misra
Mesoporous silica nanoparticles (MSNs) offer distinctive features of nano drug delivery system having large surface area and ability for surface modifications with tunable pore size as per the various biomedical applications. These multifunctional MSNs have applications in drug delivery as well as in bio-imaging. MSNs chemistries allow for conjugation of diverse moieties such as antibodies, siRNAs or ligands like folic acid. The multidrug resistant protein 1 (MRP1) (also called as the ABCC1) is known to be associated with the chemotherapy resistance. Song et al. [45] prepared MSNs with folic acid conjugated to MRP1 and evaluated their efficacy in NSCLC. The study suggested enhanced apoptosis in lung cancer cells by the nanoparticles. When in vivo studies, were carried out, these nanoparticles were able to reduce both tumor size and tumor volume due to higher accumulation of nanosized particles in the tumors.
An update on emerging drugs in osteosarcoma: towards tailored therapies?
Published in Expert Opinion on Emerging Drugs, 2019
Claudia Maria Hattinger, Maria Pia Patrizio, Federica Magagnoli, Silvia Luppi, Massimo Serra
Other ongoing phase I trials are presently recruiting HGOS patients (Table 2). These trials are evaluating the clinical efficacy of targeting ABCB1/ABCC1 with their inhibitor CBT-1® (NCT03002805) [112]; topoisomerase I with MM-398 liposomal dispersion of irinotecan (NCT02013336) [113,114]; topoisomerase II with thermosensitive liposomal doxorubicin (NCT02536183) or with liposomal encapsulated doxorubicin (DOXIL®) in association with hyperthermia (NCT02557854) [114,115]; 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase with simvastatin in association with topotecan and cyclophosphamide (NCT02390843).