Minocycline inhibits the growth of glioma by inducing autophagy

Liu, Wei Ting; Lin, Chia Ho; Hsiao, Michael; Gean, Po Wu

doi:10.4161/auto.7.2.14043

Cited by 71 publications

(56 citation statements)

References 54 publications

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“…It has been well established that autophagy is closely implicated in the occurrence and development of glioma [10, 25]. Intervening in autophagy has been accepted as one of the effective measures for glioma treatment [26, 27]. Our results, as shown in Fig.…”

Section: Discussionsupporting

confidence: 77%

Isogambogenic Acid Inhibits the Growth of Glioma Through Activation of the AMPK-mTOR Pathway

Zhao

Peng

Shu

et al. 2017

Cell Physiol Biochem

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Background/Aims: Glioma is the most devastating cancer in the brain and has a poor prognosis in adults. Therefore, there is a critical need for novel therapeutic strategies for the management of glioma patients. Isogambogenic acid, an active compound extracted from the Chinese herb Garcinia hanburyi, induces autophagic cell death. Methods: Cell viability was detected with MTT assays. Cell proliferation was assessed using the colony formation assay. Morphological changes associated with autophagy and apoptosis were tested by TEM and Hoechst staining, respectively. The apoptosis rate was measured by flow cytometry. Western blot, immunofluorescence and immunohistochemical analyses were used to detect protein expression. U87-derived xenografts were established for the examination of the effect of isogambogenic acid on glioma growth in vivo. Results: Isogambogenic acid induced autophagic death in U87 and U251 cells, and blocking late-stage autophagy markedly enhanced the antiproliferative activities of isogambogenic acid. Moreover, we observed the activation of AMPK-mTOR signalling in isogambogenic acid-treated glioma cells. Furthermore, the activation of AMPK or the inhibition of mTOR augmented isogambogenic acid-induced autophagy. Inhibition of autophagy attenuated apoptosis in isogambogenic acid-treated glioma cells. Finally, isogambogenic acid inhibited the growth of U87 glioma in vivo. Conclusion: Isogambogenic acid inhibits the growth of glioma via activation of the AMPK-mTOR signalling pathway, which may provide evidence for future clinical applications in glioma therapy.

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Section: Discussionsupporting

confidence: 77%

Isogambogenic Acid Inhibits the Growth of Glioma Through Activation of the AMPK-mTOR Pathway

Zhao

Peng

Shu

et al. 2017

Cell Physiol Biochem

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“…Furthermore, minocycline has been described to inhibit tumour growth in the xenograft tumour model of C6 glioma cells. This effect was associated with an induction of autophagic cell death, although minocycline still induced cell death through the activation of caspase-3 when autophagy was inhibited (Liu et al, 2011). Therefore, these experimental data confirm that the antiproliferative, anti-angiogenic and matrix-stimulatory activities displayed by minocycline increase its anti-metastasic and anti-tumour potential.…”

Section: Effects Of Minocycline On Cancersupporting

confidence: 71%

Minocycline: far beyond an antibiotic

Garrido-Mesa

Zarzuelo

Gálvez

2013

British J Pharmacology

763

597

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Minocycline is a second‐generation, semi‐synthetic tetracycline that has been in therapeutic use for over 30 years because of its antibiotic properties against both gram‐positive and gram‐negative bacteria. It is mainly used in the treatment of acne vulgaris and some sexually transmitted diseases. Recently, it has been reported that tetracyclines can exert a variety of biological actions that are independent of their anti‐microbial activity, including anti‐inflammatory and anti‐apoptotic activities, and inhibition of proteolysis, angiogenesis and tumour metastasis. These findings specifically concern to minocycline as it has recently been found to have multiple non‐antibiotic biological effects that are beneficial in experimental models of various diseases with an inflammatory basis, including dermatitis, periodontitis, atherosclerosis and autoimmune disorders such as rheumatoid arthritis and inflammatory bowel disease. Of note, minocycline has also emerged as the most effective tetracycline derivative at providing neuroprotection. This effect has been confirmed in experimental models of ischaemia, traumatic brain injury and neuropathic pain, and of several neurodegenerative conditions including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis and spinal cord injury. Moreover, other pre‐clinical studies have shown its ability to inhibit malignant cell growth and activation and replication of human immunodeficiency virus, and to prevent bone resorption. Considering the above‐mentioned findings, this review will cover the most important topics in the pharmacology of minocycline to date, supporting its evaluation as a new therapeutic approach for many of the diseases described herein.

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“…The activation of autophagy may lead either to cell differentiation or to cell death [21,30,31,32,33]. Autophagy is clearly implicated in cell differentiation and cell death because low doses of rapamycin activate autophagy [34].…”

Section: Discussionmentioning

confidence: 99%

High Autophagy in the Naked Mole Rat may Play a Significant Role in Maintaining Good Health

Zhao

Lin

Kan

et al. 2014

Cell Physiol Biochem

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Background/Aims: The maximum lifespan of the naked mole rat is over 28.3 years, which exceeds that of any other rodent species, suggesting that age-related changes in its body composition and functionality are either attenuated or delayed in this extraordinarily long-lived species. However, the mechanisms underlying the aging process in this species are poorly understood. In this study, we investigated whether long-lived naked mole rats display more autophagic activity than short-lived mice. Methods: Hepatic stellate cells isolated from naked mole rats were treated with 50 nM rapamycin or 20 mM 3-methyladenine (3-MA) for 12 or 24 h. Expression of the autophagy marker proteins LC3-II and beclin 1 was measured with western blotting and immunohistochemistry. The induction of apoptosis was analyzed by flow cytometry. Results: Our results demonstrate that one-day-old naked mole rats have higher levels of autophagy than one-day-old short-lived C57BL/6 mice, and that both adult naked mole rats (eight months old) and adult C57BL/6 mice (eight weeks old) have high basal levels of autophagy, which may be an important mechanism inhibiting aging and reducing the risk of age-related diseases. Conclusion: Here, we report that autophagy facilitated the survival of hepatic stellate cells from the naked mole rat, and that treatment with 3-MA or rapamycin increased the ratio of apoptotic cells to normal hepatic stellate cells.

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Minocycline inhibits the growth of glioma by inducing autophagy

Cited by 71 publications

References 54 publications

Isogambogenic Acid Inhibits the Growth of Glioma Through Activation of the AMPK-mTOR Pathway

Isogambogenic Acid Inhibits the Growth of Glioma Through Activation of the AMPK-mTOR Pathway

Minocycline: far beyond an antibiotic

High Autophagy in the Naked Mole Rat may Play a Significant Role in Maintaining Good Health

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