Raptor mediates the antiproliferation of cardamonin by mTORC1 inhibition in SKOV3 cells

Shi, Daohua; Zhu, Yanting; Niu, Peiguang; Zhou, Jintuo; Chen, Huajiao

doi:10.2147/ott.s155065

Cited by 12 publications

(15 citation statements)

References 38 publications

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“…In this study, we found that carda-monin decreased the phosphorylation of mTOR as well as the expression of NF-κB p65 nuclear protein. In addition, our previous study discovered that cardamonin decreased both the expression and phosphorylation of Raptor, indicating cardamonin may be a specific mTORC1 inhibitor [31]. Therefore, we speculate that the anti-inflammatory effects of cardamonin involve the downregulation of NF-κB activity via the mTOR pathway.…”

Section: Discussionmentioning

confidence: 72%

Anti-inflammatory Effects of Cardamonin in Ovarian Cancer Cells Are Mediated via mTOR Suppression

et al. 2018

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Cardamonin exhibits a variety of pharmacological activities including anti-inflammatory and antitumor, which are correlated with the inhibition of nuclear factor-kappaB and the mammalian target of rapamycin, respectively. However, whether the anti-inflammatory effects of cardamonin are mediated by the mammalian target of rapamycin remains unknown. In this study, ovarian cancer SKOV3 cells were cultured with lipopolysaccharide to induce inflammation, and the inhibitory effects and underlying molecular mechanisms of cardamonin were investigated using specific inhibitors of the mammalian target of rapamycin and the nuclear factor-kappaB pathway (rapamycin and pyrrolidine dithiocarbamate, respectively). Our results indicated that cardamonin inhibited the viability of normal and lipopolysaccharide-pretreated SKOV3 cells in a concentration-dependent manner. In accordance with rapamycin, the activation of the mammalian target of rapamycin and its downstream target, ribosomal protein S6 kinase 1, was inhibited by cardamonin, while pyrrolidine dithiocarbamate substantially blocked nuclear factor-kappaB activation and mildly inhibited the phosphorylation of the mammalian target of rapamycin and ribosomal protein S6 kinase 1. Pretreated with pyrrolidine dithiocarbamate, the effect of cardamonin on the mammalian target of rapamycin signalling was not affected, but the expression of inflammatory factors was further reduced. In cells pretreated with rapamycin, the inhibitory effects of cardamonin were completely suppressed with regards to the phosphorylation of the mammalian target of rapamycin, ribosomal protein S6 kinase 1, TNF-, and interleukin-6, and nuclear factor-kappaB p65 protein expression was decreased. In conclusion, our findings indicate that the anti-inflammatory effects of cardamonin are correlated with mammalian target of rapamycin inhibition.

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Section: Discussionmentioning

confidence: 72%

Anti-inflammatory Effects of Cardamonin in Ovarian Cancer Cells Are Mediated via mTOR Suppression

et al. 2018

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“…cardamonin is a specific mTorc1 inhibitor, which decreases the protein level of raptor, disrupts the interaction of mTor and raptor and interrupts the mTorc1 signalling cascade (24)(25)(26). Therefore, cardamonin inhibits mTor independent of the FrB domain and the kinase domain.…”

Section: Discussionmentioning

confidence: 99%

“…additionally, cardamonin has no effect on the phosphorylation of akt, which is decreased by aZd8055 (24). cardamonin has previously been shown to inhibit the mTorc1 signalling pathway by decreasing the protein level of raptor (24,25). You et al (26) demonstrated that cardamonin exerts cardioprotective effects in left ventricular remodelling by disrupting the mTor-raptor association, suggesting that cardamonin is a specific mTORC1 inhibitor.…”

Section: Anti-proliferative Effect Of Cardamonin On Mtor Inhibitor-resistant Cancer Cellsmentioning

confidence: 99%

Anti‑proliferative effect of cardamonin on mTOR inhibitor‑resistant cancer cells

Niu

Chen

et al. 2019

Mol Med Report

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a number of mammalian target of rapamycin (mTor) inhibitors have been approved for the treatment of certain types of cancer or are currently undergoing clinical trials. However, mTor targeted therapy exerts selective pressure on tumour cells, which leads to the preferential growth of resistant subpopulations. There are two classes of mTor inhibitors: i) The rapalogs, such as rapamycin, which bind to the 12-kda FK506-binding protein/rapamycin-binding domain of mTor; and ii) the aTP-competitive inhibitors, such as aZd8055, which block the mTor kinase domain. cardamonin inhibits mTor by decreasing the expression of regulatory-associated protein of mTor (raptor), a mechanism of action which differs from the currently available mTor inhibitors. The present study investigated the inhibitory effects of cardamonin on mTor inhibitor-resistant cancer cells. Hela cervical cancer cells and McF-7 breast cancer cells were exposed to high concentrations of mTor inhibitors, until resistant clones emerged. cytotoxicity was measured using the MTT and colony forming assays. The inhibitory effect of cardamonin on mTor signalling was assessed by western blotting. The resistant cells were less sensitive to mTor inhibitors compared with the parental cells. consistent with the anti-proliferation effect, rapamycin and aZd8055 had no effect on the phosphorylation of rapamycin-sensitive sites on ribosomal protein S6 kinase B1 (S6K1) and aZd8055-sensitive sites on protein kinase B and eukaryotic translation initiation factor 4e binding protein 1 (Thr 37/46), respectively, in rapamycin-and aZd8055-resistant cells. cardamonin inhibited cell proliferation and decreased the phosphorylation of mTor and S6K1, as well as the protein level of raptor, in the mTor inhibitor-resistant cells. Therefore, cardamonin may serve as a therapeutic agent for patients with cervical and breast cancer resistant to mTor inhibitors.

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“…(2018a) In vitro SKOV3 ↓Glycolysis, HK, LDH, ↑autophagy, LC3-II, ↑LAMP1, ↓p-S6K1, p-mTOR, HK2, ↑p-AMPK Shi et al. (2018b) In vitro SKOV3 ↓Cell viability, ↑autophagy, ↑LC3-II, ↑apoptosis, ↑caspase-3, PARP, ↓Raptor, mTOR, S6K1 Shi et al. (2018c) In vitro SKOV3, A2780 SKOV3 ↓Cell viability, colony formation ↑G2/M phase arrest, ↓XIAP, survivin, Bcl-2, ↓mTOR, p70S6K Niu et al.…”

Section: Biological Activities Of CDmentioning

confidence: 99%

Emerging roles of cardamonin, a multitargeted nutraceutical in the prevention and treatment of chronic diseases

Daimary

Dey

Rana

et al. 2021

Current Research in Pharmacology and Drug Discovery

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Although chronic diseases are often caused by the perturbations in multiple cellular components involved in different biological processes, most of the approved therapeutics target a single gene/protein/pathway which makes them not as efficient as they are anticipated and are also known to cause severe side effects. Therefore, the pursuit of safe, efficacious, and multitargeted agents is imperative for the prevention and treatment of these diseases. Cardamonin is one such agent that has been known to modulate different signaling molecules such as transcription factors (NF-κB and STAT3), cytokines (TNF-α, IL-1β, and IL-6) enzymes (COX-2, MMP-9 and ALDH1), other proteins and genes (Bcl-2, XIAP and cyclin D1), involved in the development and progression of chronic diseases. Multiple lines of evidence emerging from pre-clinical studies advocate the promising potential of this agent against various pathological conditions like cancer, cardiovascular diseases, diabetes, neurological disorders, inflammation, rheumatoid arthritis, etc., despite its poor bioavailability. Therefore, further studies are paramount in establishing its efficacy in clinical settings. Hence, the current review focuses on highlighting the underlying molecular mechanism of action of cardamonin and delineating its potential in the prevention and treatment of different chronic diseases.

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Raptor mediates the antiproliferation of cardamonin by mTORC1 inhibition in SKOV3 cells

Cited by 12 publications

References 38 publications

Anti-inflammatory Effects of Cardamonin in Ovarian Cancer Cells Are Mediated via mTOR Suppression

Anti-inflammatory Effects of Cardamonin in Ovarian Cancer Cells Are Mediated via mTOR Suppression

Anti‑proliferative effect of cardamonin on mTOR inhibitor‑resistant cancer cells

Emerging roles of cardamonin, a multitargeted nutraceutical in the prevention and treatment of chronic diseases

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