Autophagy induced by cardamonin is associated with mTORC1 inhibition in SKOV3 cells

Shi, Daohua; Niu, Peiguang; Heng, Xiaojie; Chen, Lijun; Zhu, Yanting; Zhou, Jintuo

doi:10.1016/j.pharep.2018.04.005

Cited by 23 publications

(19 citation statements)

References 38 publications

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“…We have investigated the antiproliferation effect of cardamonin in various cancer cells. It demonstrated that the efficiency-concentration ranged from 5 μM to 30 μM [ 13 , 15 , 16 ]. In the present study, the inhibitory effect of cardamonin (5, 10 and 20 μM) on the lactate secretion was measured in SKOV3 cells.…”

Section: Methodsmentioning

confidence: 99%

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Glycolysis inhibition via mTOR suppression is a key step in cardamonin-induced autophagy in SKOV3 cells

Shi

Zhao

Niu

et al. 2018

BMC Complement Altern Med

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BackgroundAutophagy occurs in cells that undergoing nutrient deprivation. Glycolysis rapidly supplies energy for the proliferation of cancer cells. Cardamonin inhibits proliferation and enhances autophagy by mTORC1 suppression in ovarian cancer cells. Here, we investigate the relationship between cardamonin-triggered autophagy and glycolysis inhibition via mTORC1 suppression.MethodsTreated with indicated compounds, ATP content and the activity of hexokinase (HK) and lactate dehydrogenase (LDH) were analyzed by the assay kits. Autophagy was detected by monodansylcadaverin (MDC) staining. The relationship between cardamonin-triggered autophagy and glycolysis inhibition via mTORC1 suppression was analyzed by Western blot.ResultsWe found that cardamonin inhibited the lactate secretion, ATP production, and the activity of HK and LDH. The results demonstrated that cardamonin enhanced autophagy in SKOV3 cells, as indicated by acidic compartments accumulation, microtubule-associated protein 1 Light Chain 3-II (LC3-II) and lysosome associated membrane protein 1 up-regulation. Our results showed that the activation of mTORC1 signaling and the expression HK2 were reduced by cardamonin; whereas the phosphorylation of AMPK (AMP-activated protein kinase) was increased. We also confirmed that the AMPK inhibitor, Compound C, reversed cardamonin-induced upregulation of LC3-II.ConclusionThese results suggest that cardamonin-induced autophagy is associated with inhibition on glycolysis by down-regulating the activity of mTORC1 in ovarian cancer cells.

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Section: Methodsmentioning

confidence: 99%

“…Cardamonin inhibits the proliferation and metastasis of various cancer cells [ 13 – 15 ]. In our previous studies, we demonstrate that the antitumor effect of cardamonin dependents on mTOR inhibition [ 16 , 17 ]. Recently, we find that the autophagy induction is account for the antiproliferative activity of cardamonin [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Glycolysis inhibition via mTOR suppression is a key step in cardamonin-induced autophagy in SKOV3 cells

Shi

Zhao

Niu

et al. 2018

BMC Complement Altern Med

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“…mTORC2 also stimulates serum and glucocorticoid-regulated kinase 1 (SGK1), a kinase that contributes to the regulation of glucose and creatine transporters, hormone release, inflammation, growth and apoptosis [57], belongs to the AGC family of protein kinases [54] and is involved in aberrant cell growth, survival and invasiveness. Nevertheless, recent findings have highlighted how mTORC2 could also act as a repressor of chaperone-mediated autophagy [58,59], which is frequently deregulated in numerous age-related disorders [60,61]. Moreover, mTORC2 increases Na + transport and regulates cell migration [62,63].…”

Section: Activity Of Mtor Complexmentioning

confidence: 99%

Targeting mTOR in Acute Lymphoblastic Leukemia

Simioni

Martelli

Zauli

et al. 2019

Cells

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Acute Lymphoblastic Leukemia (ALL) is an aggressive hematologic disorder and constitutes approximately 25% of cancer diagnoses among children and teenagers. Pediatric patients have a favourable prognosis, with 5-years overall survival rates near 90%, while adult ALL still correlates with poorer survival. However, during the past few decades, the therapeutic outcome of adult ALL was significantly ameliorated, mainly due to intensive pediatric-based protocols of chemotherapy. Mammalian (or mechanistic) target of rapamycin (mTOR) is a conserved serine/threonine kinase belonging to the phosphatidylinositol 3-kinase (PI3K)-related kinase family (PIKK) and resides in two distinct signalling complexes named mTORC1, involved in mRNA translation and protein synthesis and mTORC2 that controls cell survival and migration. Moreover, both complexes are remarkably involved in metabolism regulation. Growing evidence reports that mTOR dysregulation is related to metastatic potential, cell proliferation and angiogenesis and given that PI3K/Akt/mTOR network activation is often associated with poor prognosis and chemoresistance in ALL, there is a constant need to discover novel inhibitors for ALL treatment. Here, the current knowledge of mTOR signalling and the development of anti-mTOR compounds are documented, reporting the most relevant results from both preclinical and clinical studies in ALL that have contributed significantly into their efficacy or failure.

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“…The interaction of RAPTOR and SHOC2 has been shown to inhibit RAPTOR‐mTOR binding and induce autophagy via inactivating mTORC1, which facilitates, in parallel, RAS‐ERK activation and PDAC progression . Autophagy induced by cardamonin is associated with mTORC1 inhibition through decreasing RAPTOR in cervical cancer . Moreover, RAPTOR upregulation has been shown to contribute to PI3K‐mTOR inhibitor resistance in renal cancer, further indicating the effect of RAPTOR on mTORC1 during tumor progression and outcomes.…”

Section: Introductionmentioning

confidence: 96%

“…12 Autophagy induced by cardamonin is associated with mTORC1 inhibition through decreasing RAPTOR in cervical cancer. 13 Moreover, RAPTOR upregulation has been shown to contribute to PI3K-mTOR inhibitor resistance in renal cancer, 14 further indicating the effect of RAPTOR on mTORC1 during tumor progression and outcomes. Therefore, RAPTOR might be a favorable molecule to target in order to solve the issue of mTORC1-targeted preparations in tumor treatment.…”

Section: Introductionmentioning

confidence: 99%

RAPTOR promotes colorectal cancer proliferation by inducing mTORC1 and upregulating ribosome assembly factor URB1

et al. 2019

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Mammalian target of rapamycin complex 1 (mTORC1) is evolutionally conserved and frequently activated in various tumors, including colorectal cancer (CRC). It has been reported that the ribosome assembly factor Urb1 acts downstream of mTORC1/raptor signaling and contributes to digestive organ development in zebrafish. Previously, we highlighted that URB1 was overexpressed in CRC. Here, we assessed the mTORC1/regulatory associated protein with mTOR (RAPTOR)‐URB1 axis in CRC tumorigenesis. We found that RAPTOR was overexpressed in CRC tissues and cell lines, was a favorable predictor in patients with CRC, and positively correlated with URB1. Silencing of RAPTOR suppressed CRC cell proliferation and migration and induced cell cycle arrest and apoptosis in vitro and inhibited xenograft growth in vivo. Moreover, ectopic overexpression of RAPTOR exerted an inverse biological phenotype. Knockdown of RAPTOR quenched mTORC1 activity and reduced the expression of URB1 and cyclinA2 (CCNA2). In contrast, overexpression of RAPTOR activated mTORC1 and upregulated URB1 and CCNA2. Furthermore, URB1 and CCNA2 expression were also impeded by rapamycin, which is a specific inhibitor of mTORC1. Thus, RAPTOR promoted CRC proliferation, migration, and cell cycle progression by inducing mTORC1 signaling and transcriptional activation of both URB1 and CCNA2. Taken together, we concluded that RAPTOR has the potential to serve as a novel biomarker and therapeutic target for CRC.

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Autophagy induced by cardamonin is associated with mTORC1 inhibition in SKOV3 cells

Abstract: These findings demonstrated that the autophagy induced by cardamonin was associated with mTORC1 inhibition through decreasing the protein level of Raptor in SKOV3 cells.

Cited by 23 publications

References 38 publications

Glycolysis inhibition via mTOR suppression is a key step in cardamonin-induced autophagy in SKOV3 cells

Glycolysis inhibition via mTOR suppression is a key step in cardamonin-induced autophagy in SKOV3 cells

Targeting mTOR in Acute Lymphoblastic Leukemia

RAPTOR promotes colorectal cancer proliferation by inducing mTORC1 and upregulating ribosome assembly factor URB1

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