Anthracenedione derivative 1403P-3 induces apoptosis in KB and KBv200 cells via reactive oxygen species-independent mitochondrial pathway and death receptor pathway
“…Cell survival was calculated using the following formula: survival (%) = (mean experimental absorbance/mean control absorbance) x 100%. 38 Annexin V-FITC/PI assay. Apoptosis rate was quantified by detecting surface exposure of phosphatidylserine in apoptotic cells using Annexin V-FITC/PI (propidium iodide) apoptosis detection kit (BD Biosciences Clontech) according to the manufacturer's instruction.…”
“…Cell survival was calculated using the following formula: survival (%) = (mean experimental absorbance/mean control absorbance) x 100%. 38 Annexin V-FITC/PI assay. Apoptosis rate was quantified by detecting surface exposure of phosphatidylserine in apoptotic cells using Annexin V-FITC/PI (propidium iodide) apoptosis detection kit (BD Biosciences Clontech) according to the manufacturer's instruction.…”
“…As the major biological criterion for determination of whether a cell is apoptotic, fragmentation of chromosomal DNA is believed to be a relatively late event in the apoptotic process (Zhang et al, 2007;Huang et al, 2014). When treated with anticancer agent, chromatin DNA is cleaved into multiples of approximately 180-200 base pairs (bp) internucleosomal fragments which can be detected by gel electrophoresis as a typical DNA ladder pattern (Gonzá-lez et al, 2013;Huang et al, 2014).…”
Section: Gtp-induced Dna Fragmentation In Mcf-7 Cellsmentioning
confidence: 99%
“…Apoptosis, or programmed cell death, is a genetically regulated and organized cell death process, which plays an important role in the development and homeostasis of multicellular organisms (Pan et al, 1998;Zhang et al, 2007). Apoptosis can be induced by both external and internal stimuli such as radiation, hypoxia, viral infection, and cytotoxic agents (Cotran et al, 1999).…”
Abstract:In order to study the molecular mechanisms of green tea polyphenols (GTPs) in treatment or prevention of breast cancer, the cytotoxic effects of GTPs on five human cell lines (MCF-7, A549, Hela, PC3, and HepG2 cells) were determined and the antitumor mechanisms of GTPs in MCF-7 cells were analyzed. The results showed that GTPs exhibited a broad spectrum of inhibition against the detected cancer cell lines, particularly the MCF-7 cells. Studies on the mechanisms revealed that the main modes of cell death induced by GTPs were cell cycle arrest and mitochondrialmediated apoptosis. Flow cytometric analysis showed that GTPs mediated cell cycle arrest at both G1/M and G2/M transitions. GTP dose dependently led to apoptosis of MCF-7 cells via the mitochondrial pathways, as evidenced by induction of chromatin condensation, reduction of mitochondrial membrane potential (ΔΨ m ), improvement in the generation of reactive oxygen species (ROS), induction of DNA fragmentation, and activations of caspase-3 and caspase-9 in the present paper.
“…We used the human non-small cell lung cancer cell line H460 and its MX-selected ABCG2-overexpressing cell line H460/MX20, the human colon carcinoma cell line S1 and its MXselected ABCG2-overexpressing cell line S1-MI-80, the human breast carcinoma cell line MCF-7 and its DOX-selected ABCB1-overexpressing cell line MCF-7/adr. Stable-transfected HEK293/ pcDNA3.1, HEK293/ABCB1, and HEK293/ABCG2 (wild-type) cells were established by selection with G418 after transfecting HEK293 with empty pcDNA3.1 vector or pcDNA3.1 vector containing full-length ABCB1 or pcDNA3.1 vector containing fulllength ABCG2 coding arginine (R) at amino acid 482 position, respectively (34)(35)(36)(37), were generous gifts from Dr. Susan Bates (NCI, NIH, Bethesda, MD). Cell lines used in this study were thawed from early passage stocks and were passaged for less than 6 months.…”
The overexpression of ATP-binding cassette (ABC) transporters has been proved to be a major trigger for multidrug resistance (MDR) in certain types of cancer. In our study, we investigated whether osimertinib (AZD9291), a third-generation irreversible tyrosine kinase inhibitor of both activating EGFR mutations and resistance-associated T790M point mutation, could reverse MDR induced by ABCB1 and ABCG2 in vitro, in vivo, and ex vivo. Our results showed that osimertinib significantly increased the sensitivity of ABCB1-and ABCG2-overexpressing cells to their substrate chemotherapeutic agents in vitro and in the model of ABCB1-overexpressing KBv200 cell xenograft in nude mice. Mechanistically, osimertinib increased the intracellular accumulations of doxorubicin (DOX) and Rhodamine 123 (Rho 123) by inhibiting the efflux function of the transporters in ABCB1-or ABCG2-overexpressing cells but not in their parental sensitive cells. Furthermore, osimertinib stimulated the ATPase activity of both ABCB1 and ABCG2 and competed with the [ 125 I] iodoarylazidoprazosin photolabeling bound to ABCB1 or ABCG2, but did not alter the localization and expression of ABCB1 or ABCG2 in mRNA and protein levels nor the phosphorylations of EGFR, AKT, and ERK. Importantly, osimertinib also enhanced the cytotoxicity of DOX and intracellular accumulation of Rho 123 in ABCB1-overexpressing primary leukemia cells. Overall, these findings suggest osimertinib reverses ABCB1-and ABCG2-mediated MDR via inhibiting ABCB1 and ABCG2 from pumping out chemotherapeutic agents and provide possibility for cancer combinational therapy with osimertinib in the clinic.
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