Different regulatory pathways are involved in the proliferative inhibition of two types of leukemia cell lines induced by paclitaxel

Xia, Rui-Long; Lü, Yan; Zhu, Luping; Zhang, Shifu; Zhao, Fukun; Fu, Caiyun

doi:10.3892/or.2013.2624

Cited by 8 publications

(10 citation statements)

References 24 publications

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“…Paclitaxel exhibits a high antitumor efficacy and is able to suppress cancer cell proliferation through the inhibition of mitosis (17). The results of the present study demonstrated that A549 cell proliferation was markedly inhibited, in a time-dependent manner, by paclitaxel, which is consistent with previous studies (18). However, the rate of paclitaxel-induced growth inhibition was markedly decreased in A549-F10 cells compared with the negative control, suggesting that the overexpression of F10 inhibited chemosensitivity to paclitaxel in A549 lung cancer cells.…”

Section: Discussionsupporting

confidence: 93%

F10, a novel hydatidiform mole-associated gene, inhibits the paclitaxel sensitivity of A549 lung cancer cells by downregulating BAX and caspase-3

et al. 2017

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F10 is a novel hydatidiform mole (HM)-associated gene that was initially identified during a study into the pathogenesis of HMs. However, the role of the F10 gene requires further investigation. Our, previous studies have indicated that F10 may be involved in the malignant transformation of HMs and the development of certain types of adenocarcinoma, and that the overexpression of F10 may lead to excessive proliferation and decreased apoptosis of A549 cells. The present study aimed to investigate whether F10 may suppress the sensitivity of A549 lung cancer cells to paclitaxel therapy. A previously established F10-overexpressing A549 cell line (A549-F10) was treated with paclitaxel, using untransfected A549 cells and A549-mock cells (non-carrier A549) as the controls. These three groups of cells were subsequently examined by an MTT cell proliferation assay and a TUNEL-fluorescein isothiocyanate/Hoechst 33258 apoptosis assay. A western blot analysis was used to determine the expression levels of the pro-apoptotic genes B-cell lymphoma-2-associated X protein (BAX) and caspase-3. The effects of paclitaxel treatment on the proliferation and apoptosis of A549 cells were compared between the aforementioned cell lines. It was revealed that F10 inhibited the chemosensitivity of A549 cells to paclitaxel, as demonstrated by the decreased rates of growth inhibition and apoptosis in the A549-F10 group compared with the two control groups. Furthermore, the A549-F10 cells treated with paclitaxel exhibited significantly lower expression levels of the pro-apoptotic genes. The results of the current study demonstrate that F10 may inhibit the chemosensitivity of A549 cells to paclitaxel and that this inhibitory effect may be mediated by the downregulation of BAX and caspase-3 expression, which subsequently inhibits cell apoptosis.

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Section: Discussionsupporting

confidence: 93%

F10, a novel hydatidiform mole-associated gene, inhibits the paclitaxel sensitivity of A549 lung cancer cells by downregulating BAX and caspase-3

et al. 2017

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“…Apoptosis is a proactive cell death process in which cells undergo a certain stimulus to maintaining the stability of the internal environment, The morphological alterations of apoptosis are characterized by cell shrinkage, chromatin condensation, nuclear fragmentation, DNA degradation, and apoptotic body formation ( 27 ). Paclitaxel may arrest the division of cancer cells in the G 2 /M-phase and elevate the expression of cyclinB1 ( 28 , 29 ). In the present study, paclitaxel-treated CHMm cells exhibited morphological alterations characteristic of apoptosis, including cell shrinkage, intracellular vacuolization and chromatin condensation.…”

Section: Discussionmentioning

confidence: 99%

Paclitaxel suppresses proliferation and induces apoptosis through regulation of ROS and the AKT/MAPK signaling pathway in canine mammary gland tumor cells

et al. 2018

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Paclitaxel is a diterpenoid compound, derived from the pacific yew (Taxus brevifolia) berry, which exhibits antineoplastic effects against various types of cancer. However, the antitumor effects and the molecular mechanisms of paclitaxel on canine CHMm cells remain to be elucidated. The aim of the present study was to investigate the antitumor effects of paclitaxel on CHMm cells and identify relevant signal transduction pathways modulated by paclitaxel using multiple methods including MTT assay, flow cytometry, acridine orange/ethidium bromide staining, transmission electron microscopy, determination of cellular reactive oxygen species (ROS), superoxide dismutase (SOD) and malondiadehyde (MDA) and western blotting, the data indicated that paclitaxel decreased cell viability, induced G2/M-phase cell cycle arrest, suppressed the expression of cyclin B1 and induced apoptosis in a dose-dependent manner. In addition, paclitaxel upregulated the expression of Bax and cytochrome c, but reduced expression of apoptosis regulator Bcl-2, resulting in activation of caspase-3, chromatin condensation, karyopyknosis, intracellular vacuolization, increased production of ROS and MDA, and decreased activity of SOD. However, these effects were inhibited when CHMm cells were treated with N-acetyl-L-cysteine. Furthermore, treatment with paclitaxel inhibited the level of of phospho (p)-RAC-α serine/threonine-protein kinase (AKT) and p-ribosomal protein S6 kinase proteins, and promoted phosphorylation of P38 mitogen-activated protein kinase (MAPK) and p-90 kDa ribosomal protein S6 kinase 1 proteins in CHMm cells. It was observed that paclitaxel in combination with pharmacological inhibitors of the P38 and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) signaling pathways (SB203580 and LY294002, respectively) exerted synergistic inhibitory effects on the proliferation of the CHMm cells. The results of the present study demonstrated that paclitaxel inhibited tumor cell proliferation by increasing intrinsic apoptosis through inhibition of the PI3K/AKT signaling pathway and activation of MAPK signaling pathway in CHMm cells.

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“…Propidium iodide (PI, BestBio biotechnologies, Shanghai, China) (10 μg/ml, 50 μl) or Hoechst 33342 (Beyotime Institute of Biotechnology, China; 10 μg/ml, 50 μl) was added. After incubation at room temperature for 5 minutes in the dark, image analysis was performed through an inverted fluorescence microscope (TE2000-U, Nikon, Tokyo, Japan) as described previously 36 37 .…”

Section: Methodsmentioning

confidence: 99%

PFR peptide, one of the antimicrobial peptides identified from the derivatives of lactoferrin, induces necrosis in leukemia cells

Lü

Zhang

Shi

et al. 2016

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LF11-322 (PFWRIRIRR-NH2) (PFR peptide), a nine amino acid-residue peptide fragment derived from human lactoferricin, possesses potent cytotoxicity against bacteria. We report here the discovery and characterization of its antitumor activity in leukemia cells. PFR peptide inhibited the proliferation of MEL and HL-60 leukemia cells by inducing cell death in the absence of the classical features of apoptosis, including chromatin condensation, Annexin V staining, Caspase activation and increase of abundance of pro-apoptotic proteins. Instead, necrotic cell death as evidenced by increasing intracellular PI staining and LDH release, inducing membrane disruption and up-regulating intracellular calcium level, was observed following PFR peptide treatment. In addition to necrotic cell death, PFR peptide also induced G0/G1 cell cycle arrest. Moreover, PFR peptide exhibited favorable antitumor activity and tolerability in vivo. These findings thus provide a new clue of antimicrobial peptides as a potential novel therapy for leukemia.

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Different regulatory pathways are involved in the proliferative inhibition of two types of leukemia cell lines induced by paclitaxel

Cited by 8 publications

References 24 publications

F10, a novel hydatidiform mole-associated gene, inhibits the paclitaxel sensitivity of A549 lung cancer cells by downregulating BAX and caspase-3

F10, a novel hydatidiform mole-associated gene, inhibits the paclitaxel sensitivity of A549 lung cancer cells by downregulating BAX and caspase-3

Paclitaxel suppresses proliferation and induces apoptosis through regulation of ROS and the AKT/MAPK signaling pathway in canine mammary gland tumor cells

PFR peptide, one of the antimicrobial peptides identified from the derivatives of lactoferrin, induces necrosis in leukemia cells

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