Minocycline inhibits growth of epithelial ovarian cancer

Pourgholami, Mohammad H.; Mekkawy, Ahmed H.; Badar, Samina; Morris, David L.

doi:10.1016/j.ygyno.2012.01.006

Cited by 35 publications

(33 citation statements)

References 40 publications

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“…There is compelling preclinical evidence that minocycline along with a number of other tetracyclines have potent antitumorigenic and antimetastatic properties in a variety of tumors including leukemia (6), melanoma (7), renal, prostate (8), and breast cancer (9). Along this line, we have recently reported the preliminary results showing that minocycline inhibits growth of human ovarian cancer xenografts (10,11) and also suppresses ovarian cancer-induced malignant ascites formation (10). We have also established that minocycline treatment of preclinical models of ovarian cancer modulates specific transcriptional and signal transduction cascades that lead to cell-cycle arrest, apoptosis, and downregulation of angiogenesis and metastasis (10)(11)(12).…”

Section: Introductionmentioning

confidence: 91%

“…Along this line, we have recently reported the preliminary results showing that minocycline inhibits growth of human ovarian cancer xenografts (10,11) and also suppresses ovarian cancer-induced malignant ascites formation (10). We have also established that minocycline treatment of preclinical models of ovarian cancer modulates specific transcriptional and signal transduction cascades that lead to cell-cycle arrest, apoptosis, and downregulation of angiogenesis and metastasis (10)(11)(12). The exact mechanism by which minocycline mediates these anticancer effects remains to be elucidated.…”

Section: Introductionmentioning

confidence: 95%

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RETRACTED: Minocycline Targets the NF-κB Nexus through Suppression of TGF-β1-TAK1-IκB Signaling in Ovarian Cancer

Ataie-Kachoie

Badar

Morris

et al. 2013

Molecular Cancer Research

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Substantial evidence supports the critical role of NF-kB in ovarian cancer. Minocycline, a tetracycline, has been shown to exhibit beneficial effects in this malignancy through regulation of a cohort of genes that overlap significantly with the NF-kB transcriptome. Here, it was examined whether or not the molecular mechanism could be attributed to modulation of NF-kB signaling using a combination of in vitro and in vivo models. Minocycline suppressed constitutive NF-kB activation in OVCAR-3 and SKOV-3 ovarian carcinoma cells and was correlated with attenuation of IkBa kinase (IKK) activation, IkBa phosphorylation and degradation, and p65 phosphorylation and nuclear translocation. The inhibition of IKK was found to be associated with suppression of TGF-b-activated-kinase-1 (TAK1) activation and its dissociation from TAK1-binding-protein-1 (TAB1), an indispensable functional mediator between TGF-b and TAK1. Further studies demonstrated that minocycline downregulated TGF-b1 expression. Enforced TGF-b1 expression induced NF-kB activity, and minocycline rescued this effect. Consistent with this finding, TGF-b1 knockdown suppressed NF-kB activation and abrogated the inhibitory effect of minocycline on this transcription factor. These results suggest that the minocycline-induced suppression of NF-kB activity is mediated, in part, through inhibition of TGF-b1. Furthermore, the influence of minocycline on NF-kB pathway activation was examined in female nude mice harboring intraperitoneal OVCAR-3 tumors. Both acute and chronic administration of minocycline led to suppression of p65 phosphorylation and nuclear translocation accompanied by downregulation of NF-kB activity and endogenous protein levels of its target gene products. These data reveal the therapeutic potential of minocycline as an agent targeting the pro-oncogenic TGF-b-NF-kB axis in ovarian cancer.

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Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 95%

RETRACTED: Minocycline Targets the NF-κB Nexus through Suppression of TGF-β1-TAK1-IκB Signaling in Ovarian Cancer

Ataie-Kachoie

Badar

Morris

et al. 2013

Molecular Cancer Research

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“…Antitumor effects of doxy and mino have been reported in several cancer cell lines with IC 50ies between 10 and 30 mg/ml [7,8,11], but no genotoxic or cytotoxic effects were observed in lymphocytes [12]. Tolemeo et al reported IC 50 of doxy in HL-60 cells to be 8 mg/ml [13].…”

Section: Effect Of Tcnas On Viability Of Leukemic Cell Linesmentioning

confidence: 99%

“…Doxy-induced apoptosis was associated with loss of Djm, cytochrome C (cytC) release, Bcl-xL inhibition, caspase activation and intracellular ROS formation in colorectal and pancreatic cancer cell lines [6,7]. Minoinduced apoptosis was associated with caspase-3 activation and PARP-1 inhibition in ovarian cancer [8].…”

Section: Introductionmentioning

confidence: 99%

DNA damage, lysosomal degradation and Bcl-xL deamidation in doxycycline- and minocycline-induced cell death in the K562 leukemic cell line

Fares

Abedi‐Valugerdi

Hassan

et al. 2015

Biochemical and Biophysical Research Communications

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We investigated mechanisms of cytotoxicity induced by doxycycline (doxy) and minocycline (mino) in the chronic myeloid leukemia K562 cell line. Doxy and mino induced cell death in exposure-dependent manner. While annexin V/propidium iodide staining was consistent with apoptosis, the morphological changes in Giemsa staining were more equivocal. A pancaspase inhibitor Z-VAD-FMK partially reverted cell death morphology, but concurrently completely prevented PARP cleavage. Mitochondrial involvement was detected as dissipation of mitochondrial membrane potential and cytochrome C release. DNA double strand breaks detected with γH2AX antibody and caspase-2 activation were found early after the treatment start, but caspase-3 activation was a late event. Decrement of Bcl-xL protein levels and electrophoretic shift of Bcl-xL molecule were induced by both drugs. Phosphorylation of Bcl-xL at serine 62 was ruled out. Similarly, Bcr/Abl tyrosine kinase levels were decreased. Lysosomal inhibitor chloroquine restored Bcl-xL and Bcr/Abl protein levels and inhibited caspase-3 activation. Thus, the cytotoxicity of doxy and mino in K562 cells is mediated by DNA damage, Bcl-xL deamidation and lysosomal degradation with activation of mitochondrial pathway of apoptosis.

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“…Several studies have reported the cytoprotective benefits of minocycline for the treatment of stroke, cerebral ischemia, multiple sclerosis, and traumatic brain injury [3][4][5]. Minocycline has also been shown to inhibit the proliferation of several types of cancer cells (e.g., prostate, ovarian, and breast) both in vitro and in vivo, while having no effect on non-cancerous primary human cells [6,7]. Previous studies have shown that minocycline appears to be effective for chemical pleurodesis for malignant pleural effusion from lung cancer, the possible molecular mechanisms involved in pleural inflammation are induced by transforming growth factor beta and vascular endothelial growth factor [8,9].…”

Section: Introductionmentioning

confidence: 99%

Minocycline enhances mitomycin C-induced cytotoxicity through down-regulating ERK1/2-mediated Rad51 expression in human non-small cell lung cancer cells

Wang

Chang

et al. 2015

Biochemical Pharmacology

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Minocycline inhibits growth of epithelial ovarian cancer

Cited by 35 publications

References 40 publications

RETRACTED: Minocycline Targets the NF-κB Nexus through Suppression of TGF-β1-TAK1-IκB Signaling in Ovarian Cancer

RETRACTED: Minocycline Targets the NF-κB Nexus through Suppression of TGF-β1-TAK1-IκB Signaling in Ovarian Cancer

DNA damage, lysosomal degradation and Bcl-xL deamidation in doxycycline- and minocycline-induced cell death in the K562 leukemic cell line

Minocycline enhances mitomycin C-induced cytotoxicity through down-regulating ERK1/2-mediated Rad51 expression in human non-small cell lung cancer cells

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