Modulation of signal transduction pathways by natural compounds in cancer

Ranjan, Alok; Fofaria, Neel M.; Kim, Sung Hoon; Srivastava, Sanjay

doi:10.1016/s1875-5364(15)30073-x

Cited by 31 publications

(23 citation statements)

References 137 publications

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“…The anti-tumoral effect of piperine was described over fifteen years ago [44]. Since then, several studies have shown that the natural amide present potential as an anti-cancer agent, as it inhibits several aspects related to cancer progression and metastasis [71][72][73]. The EMT process is characterized by morphological, phenotypic and biochemical alterations, which together influence the behavior of tumor cells of epithelial origin [74].…”

Section: Discussionmentioning

confidence: 99%

Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells

et al. 2020

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Background: Piperine, an amide extracted from the Piper spices, exhibits strong anti-tumor properties. However, its effect on the epithelial–mesenchymal transition (EMT) process has never been investigated. Herein, we evaluate the toxic effect of piperine on lung adenocarcinoma (A549), breast adenocarcinoma (MDA-MB-231) and hepatocellular carcinoma (HepG2) cell lines, as well as its ability to inhibit EMT-related events induced by TGF-β1 treatment. Methods: The cell viability was investigated by MTT assay. Protein expression was evaluated by Western blot. Gene expression was monitored by real-time PCR. Zymography assay was employed to detect metalloproteinase (MMP) activity in conditioned media. Cell motility was assessed by the wound-healing and phagokinetic gold sol assays. Results: The results revealed that piperine was cytotoxic in concentrations over 100 µM, showing IC50 values for HepG2, MDA-MB-231 and A549 cell lines of 214, 238 and 198 µM, respectively. In order to investigate whether piperine would reverse the TGF-β1 induced-EMT, the A549 cell line was pretreated with sublethal concentrations of the natural amide followed by the addition of TGF-β1. Besides disrupting EMT-related events, piperine also inhibited both ERK 1/2 and SMAD 2 phosphorylation. Conclusions: These results suggest that piperine might be further used in therapeutic strategies for metastatic cancer and EMT-related disorders.

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Section: Discussionmentioning

confidence: 99%

Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells

et al. 2020

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“…In this regard, the identification and development of naturally occurring compounds and their derivatives have greatly contributed to this request. A growing body of evidence suggests that many natural compounds are now used in cancer chemotherapy to enhance the therapeutic efficacy of chemotherapy drugs, helping to by-pass cancer drug resistance or reduce side-effects (D'Angelo et al, 2017;Ranjan, Fofaria, Kim, & Srivastava, 2015).…”

Section: Discussionmentioning

confidence: 99%

AdoMet triggers apoptosis in head and neck squamous cancer by inducing ER stress and potentiates cell sensitivity to cisplatin

Mosca

Pagano

Ilisso

et al. 2018

Journal Cellular Physiology

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S‐Adenosyl‐l‐methionine (AdoMet) is a naturally and widely occurring sulfonium compound that plays a primary role in cell metabolism and acts as the principal methyl donor in many methylation reactions. AdoMet also exhibits antiproliferative and proapoptotic activities in different cancer cells. However, the molecular mechanisms underlying the effects exerted by AdoMet have only been partially studied. In the current study, we evaluated the antiproliferative effect of AdoMet on Cal‐33 oral and JHU‐SCC‐011 laryngeal squamous cancer cells to define the underlying mechanisms. We demonstrated that AdoMet induced apoptosis in Cal‐33 and JHU‐SCC‐011 cells, involving a caspase‐dependent mechanism paralleled by an increased Bax/Bcl‐2 ratio. Moreover, we showed, for the first time, that AdoMet induced ER‐stress in Cal‐33 cells and activated the unfolded protein response, which can be responsible for apoptosis induction through the activation of CHOP and JNK. In addition, AdoMet‐induced ER‐stress was followed by autophagy with a consistent increase in the levels of the autophagic marker LC3B‐II, which was indeed potentiated by the autophago‐lysosome inhibitor chloroquine. As both escape from apoptosis and decreased activation of JNK are mechanisms of resistance to cisplatin (cDPP), an agent usually used in cancer therapy, we have evaluated the effects of AdoMet in combination with cDPP on Cal‐33 cells. Our data showed that the combined treatment resulted in a strong synergism in inhibiting cell proliferation and in enhancing apoptosis via intrinsic mechanism. These results demonstrate that AdoMet has ER‐stress‐mediated antiproliferative activity and synergizes with cDDP on cell growth inhibition, thus providing the basis for its use in new anticancer strategies.

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“…Various physiological benefits of piperine treatment have been reported, including anti-inflammatory, anti-cancer, anti-oxidant, and hepatoprotective effects131415. Piperine has been shown to reverse hepatic steatosis and insulin resistance in mice by regulating AMPK, while also reducing obesity by regulating lipid metabolism1617.…”

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confidence: 99%

Piperine regulates UCP1 through the AMPK pathway by generating intracellular lactate production in muscle cells

Kim

Nam

Kang

et al. 2017

Sci Rep

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This study characterizes the human metabolic response to piperine, a curcumin extract, and the details of its underlying molecular mechanism. Using 1H-NMR-based metabolome analysis, we showed the metabolic effect of piperine on skeletal muscle and found that piperine increased the level of intracellular lactate, an important metabolic intermediate that controls expression of several genes involved in mitochondrial activity. Piperine also induced the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target, acetyl-CoA carboxylase (ACC), while additionally stimulating glucose uptake in an AMPK dependent manner. Piperine also stimulates the p38 mitogen-activated protein kinase (p38 MAPK), an effect that was reversed by pretreatment with compound C, an AMPK inhibitor. Inhibition of p38 MAPK resulted in no piperine-induced glucose uptake. Increased level of lactate resulted in increased expression of mitochondrial uncoupling protein 1 (UCP1), which regulates energy expenditure, thermogenesis, and fat browning. Knock-down of AMPK blocked piperine-induced UCP1 up-regulation, demonstrating the required role of AMPK in this effect. Taken together, these results suggest that piperine leads to benign metabolic effects by activating the AMPK-p38 MAPK signaling pathway and UCP1 expression by activating intracellular lactate production in skeletal muscle.

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Modulation of signal transduction pathways by natural compounds in cancer

Cited by 31 publications

References 137 publications

Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells

Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells

AdoMet triggers apoptosis in head and neck squamous cancer by inducing ER stress and potentiates cell sensitivity to cisplatin

Piperine regulates UCP1 through the AMPK pathway by generating intracellular lactate production in muscle cells

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