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

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

doi:10.3892/mmr.2019.10898

Cited by 10 publications

(10 citation statements)

References 39 publications

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“…Several studies have reported that cardamonin exerts its cytotoxic activity via inhibition of mTOR signalling [22][23][24]. A further study showed that cardamonin reduced the expression level of phosphorylated Akt, which is an upstream regulator of mTOR [25].…”

Section: Compound 19 Exerted Its Cytotoxic Activity In Mda-mb-468 and Panc-1 Cells Via Inhibition Of Akt/4ebp1 Signalling And Downregulatmentioning

confidence: 97%

Novel Semi-Synthetic Cu (II)–Cardamonin Complex Exerts Potent Anticancer Activity against Triple-Negative Breast and Pancreatic Cancer Cells via Inhibition of the Akt Signaling Pathway

et al. 2021

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Cardamonin is a polyphenolic natural product that has been shown to possess cytotoxic activity against a variety of cancer cell lines. We previously reported the semi-synthesis of a novel Cu (II)–cardamonin complex (19) that demonstrated potent antitumour activity. In this study, we further investigated the bioactivity of 19 against MDA-MB-468 and PANC-1 cancer cells in an attempt to discover an effective treatment for triple-negative breast cancer (TNBC) and pancreatic cancer, respectively. Results revealed that 19 abolished the formation of MDA-MB-468 and PANC-1 colonies, exerted growth-inhibitory activity, and inhibited cancer cell migration. Further mechanistic studies showed that 19 induced DNA damage resulting in gap 2 (G2)/mitosis (M) phase arrest and microtubule network disruption. Moreover, 19 generated reactive oxygen species (ROS) that may contribute to induction of apoptosis, corroborated by activation of caspase-3/7, PARP cleavage, and downregulation of Mcl-1. Complex 19 also decreased the expression levels of p-Akt and p-4EBP1, which indicates that the compound exerts its activity, at least in part, via inhibition of Akt signalling. Furthermore, 19 decreased the expression of c-Myc in PANC-1 cells only, which suggests that it may exert its bioactivity via multiple mechanisms of action. These results demonstrate the potential of 19 as a therapeutic agent for TNBC and pancreatic cancer.

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Section: Compound 19 Exerted Its Cytotoxic Activity In Mda-mb-468 and Panc-1 Cells Via Inhibition Of Akt/4ebp1 Signalling And Downregulatmentioning

confidence: 97%

Novel Semi-Synthetic Cu (II)–Cardamonin Complex Exerts Potent Anticancer Activity against Triple-Negative Breast and Pancreatic Cancer Cells via Inhibition of the Akt Signaling Pathway

et al. 2021

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“…However, further experiments are required to con rm the relationship between ROS production and apoptosis induction by 19 in the cancer cells. Several studies have reported that cardamonin exerted its cytotoxic activity via inhibition of mTOR signaling [23][24][25]. A further study has shown that cardamonin reduced the expression level of phosphorylated Akt, which is an upstream regulator of mTOR [26].…”

Section: Compound 19 Induced Caspase-dependent Apoptosis and Ros Genementioning

confidence: 98%

Novel semi-synthetic Cu (II)-cardamonin complex exerts potent anticancer activity against triple negative breast and pancreatic cancer cells via inhibition of the Akt signaling pathway

Hossan

Break

Bradshaw

et al. 2021

Preprint

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Triple negative breast cancer (TNBC) and pancreatic cancer are two of the most aggressive types of cancer that lack effective treatments. We have previously reported the semi-synthesis of a novel Cu (II)-cardamonin complex (19) that demonstrated potent anti-tumour activity. In this study, we further investigated the bioactivity and mode of action of 19 against MDA-MB-468 and PANC-1 cancer cells in an attempt to discover an effective anticancer agent for TNBC and pancreatic cancer, respectively. Results revealed that 19 abolished formation of MDA-MB-468 and PANC-1 colonies, exerted growth inhibitory activity and inhibited the migration of cancer cells. Further mechanistic studies showed that it induced DNA damage resulting in G2/M-phase arrest and microtubule network disruption. Moreover, there was an increase in ROS production which may have contributed to the observed induction of apoptosis, corroborated by activation of caspase-3/7, cleavage of PARP and downregulation of Mcl-1. Complex 19 also decreased the expression levels of p-Akt and p-4EBP1 in both cell lines, which indicates that the compound exerted its activity, at least in part, via inhibition of the Akt signaling pathway. Furthermore, it decreased the expression of c-Myc in PANC-1 cells only which suggests that it may exert its bioactivity via multiple mechanisms of action pertinent to tumourigenesis. These results demonstrate the potential of 19 as a promising therapeutic agent for TNBC and pancreatic cancer.

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“…Furthermore, CD downregulated cyclin D1 and activated caspase-3, and suppressed xenograft breast tumors in mice (Kong et al., 2019). Recent studies have shown that CD inhibited breast cancer cell growth and proliferation via targeting HIF-1α and mTOR/p70S6K pathway ( Jin et al., 2019 ; Niu et al., 2020 ).…”

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

Cited by 10 publications

References 39 publications

Novel Semi-Synthetic Cu (II)–Cardamonin Complex Exerts Potent Anticancer Activity against Triple-Negative Breast and Pancreatic Cancer Cells via Inhibition of the Akt Signaling Pathway

Novel Semi-Synthetic Cu (II)–Cardamonin Complex Exerts Potent Anticancer Activity against Triple-Negative Breast and Pancreatic Cancer Cells via Inhibition of the Akt Signaling Pathway

Novel semi-synthetic Cu (II)-cardamonin complex exerts potent anticancer activity against triple negative breast and pancreatic cancer cells via inhibition of the Akt signaling pathway

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

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