Piperine inhibits colorectal cancer migration and invasion by regulating STAT3/Snail-mediated epithelial–mesenchymal transition

Song, Lingyu; Wang, Yan; Zhen, Yunhuan; Li, Dengke; He, Xidong; Yang, Hong; Zhang, Huayang; Liu, Qi

doi:10.1007/s10529-020-02923-z

Cited by 38 publications

(20 citation statements)

References 18 publications

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“…To date, there are no available data showing the impact of direct STAT3 inhibitors on SNAIL 1 and SNAIL 2 expression and/or the induction of EMT in various ovarian cancer cell lines. Nevertheless, the compounds directly inhibiting STAT3 significantly reduced SNAIL expression and diminished EMT in osteosarcoma cells [64] and colorectal cancer [65]. The discussed results indicate the universal character of STAT3 in the maintenance of both SNAIL 1 and SNAIL 2 expression in ovarian cancer cell lines, independently of cells' origin, basal invasive potential or their resistance to cisplatin.…”

Section: Discussionmentioning

confidence: 83%

Impact of Selected Signaling Proteins on SNAIL 1 and SNAIL 2 Expression in Ovarian Cancer Cell Lines in Relation to Cells’ Cisplatin Resistance and EMT Markers Level

Kiełbik

Szulc-Kiełbik

Klink

2021

IJMS

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It has been increasingly recognized that SNAIL1 and SNAIL2, as major EMT-inducers, might also be involved in drug resistance of cancer cells. We sought to determine a relation between SNAIL1/2, E-cadherin and N-cadherin expression, as well as ovarian cancer cells’ resistance to cisplatin and EMT markers’ level. Thus, four ovarian cancer cell lines, were used: A2780, A2780cis, SK-OV-3 and OVCAR-3. We assessed the impact of ERK1/2, AKT and STAT3 proteins (chosen by the profiling activity of over 40 signaling proteins) on SNAIL1/2 expression, along with E-cadherin and N-cadherin levels. We showed that expression of SNAIL1 and N-cadherin are the highest in cisplatin-resistant A2780cis and SK-OV-3 cells, while high SNAIL2 and E-cadherin levels were observed in cisplatin-sensitive A2780 cells. The highest E-cadherin level was noticed in OVCAR-3 cells. SNAIL1/2 expression was dependent on ERK1/2 activity in cisplatin-resistant and potentially invasive SK-OV-3 and OVCAR-3 cells. STAT-3 regulates expression of SNAIL1/2 and leads to the so-called “cadherin switch” in cancer cells, independently of their chemoresistance. In conclusion, SNAIL1, but not SNAIL2, seems to be involved in ovarian cancer cells’ cisplatin resistance. STAT3 is a universal factor determining the expression of SNAIL1/2 in ovarian cancer cells regardless of their chemoresitance or invasive capabilities.

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Section: Discussionmentioning

confidence: 83%

Impact of Selected Signaling Proteins on SNAIL 1 and SNAIL 2 Expression in Ovarian Cancer Cell Lines in Relation to Cells’ Cisplatin Resistance and EMT Markers Level

Kiełbik

Szulc-Kiełbik

Klink

2021

IJMS

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“…Furthermore, piperine downregulated ERK and small mother against decapentaplegic (SMAD) signaling pathways [31,49], which represent upstream events of TGF-β1-induced EMT. The inhibition of cancer cells' migration by piperine via EMT suppression was recently demonstrated in colon cancer cell models [40], where piperine reduced the phosphorylation of STAT-3 and the expression of the EMT regulator Snail, whose inhibition is accompanied by upregulation of the epithelial marker E-cadherin and downregulation of the mesenchymal marker vimentin [40] (Table 2).…”

Section: Inhibition Of Invasion/migration and Epithelial Mesenchymal mentioning

confidence: 92%

“…The signal transducer and activator of transcription 3 (STAT-3) is an antiapoptotic protein playing an important role in cancer cell proliferation, invasion, and migration [83]. In prostate, gastric, and colon cancer cell models, piperine inhibited migration via STAT-3 downregulation [33,40,84] (Table 2), resulting in inhibition of metastasization.…”

Section: Inhibition Of Invasion/migration and Epithelial Mesenchymal mentioning

confidence: 99%

Overview of the Anticancer Potential of the “King of Spices” Piper nigrum and Its Main Constituent Piperine

Turrini

Sestili

Fimognari

2020

Toxins

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The main limits of current anticancer therapy are relapses, chemoresistance, and toxic effects resulting from its poor selectivity towards cancer cells that severely impair a patient’s quality of life. Therefore, the discovery of new anticancer drugs remains an urgent challenge. Natural products represent an excellent opportunity due to their ability to target heterogenous populations of cancer cells and regulate several key pathways involved in cancer development, and their favorable toxicological profile. Piper nigrum is one of the most popular spices in the world, with growing fame as a source of bioactive molecules with pharmacological properties. The present review aims to provide a comprehensive overview of the anticancer potential of Piper nigrum and its major active constituents—not limited to the well-known piperine—whose undeniable anticancer properties have been reported for different cancer cell lines and animal models. Moreover, the chemosensitizing effects of Piper nigrum in association with traditional anticancer drugs are depicted and its toxicological profile is outlined. Despite the promising results, human studies are missing, which are crucial for supporting the efficacy and safety of Piper nigrum and its single components in cancer patients.

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“…Therefore, Neferine may play a certain anti-tumor effects by regulating the invasiveness and chemosensitivity of cancer cells through EMT [ 134 ]. Piperine reverses the biomarker expression of EMT, and inhibits colorectal cancer migratory and invasive capacities through STAT3/Snail mediated EMT [ 142 ]. An interesting study by Karolina Wojtowicz et analyzed the cytotoxic effect of piperine and cytostatic drugs throug MTT assay.…”

Section: Role Of Alkaloids In Tmementioning

confidence: 99%

“…Berberine induced EMT changes in colonic epithelial cells with decreased E-cadherin and increased vimentin and α-SMA expression Halofuginone inhibits phosphorylation of SMAD proteins in response to TGF-β. Neferine suppressed EMT through an upregulation of E-cadherin and downregulation of Vimentin, Snail and N-cadherin and TGF-β [ 2 , 8 , 39 , 134 – 142 ] ECM MMPs Morphine reducts the circulating MMP-9 and u-PA through modulation of paracrine communication between cancer cells and non-malignant cells in the tumor microenvironment. Emetine regulates two major MAPKs, p38 and ERK.This leads to the selective down-regulation of MMP-2 and MMP-9 [ 3 , 146 , 147 ] ROS – Koumine possesses the cytoprotective effects by suppressing production of ROS、caspase-3 activity and influencing the expression of Bax and Bcl-2.…”

Section: Introductionmentioning

confidence: 99%

Tumor microenvironment: a prospective target of natural alkaloids for cancer treatment

Luo

Yin

et al. 2021

Cancer Cell Int

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Malignant tumor has become one of the major diseases that seriously endangers human health. Numerous studies have demonstrated that tumor microenvironment (TME) is closely associated with patient prognosis. Tumor growth and progression are strongly dependent on its surrounding tumor microenvironment, because the optimal conditions originated from stromal elements are required for cancer cell proliferation, invasion, metastasis and drug resistance. The tumor microenvironment is an environment rich in immune/inflammatory cells and accompanied by a continuous, gradient of hypoxia and pH. Overcoming immunosuppressive environment and boosting anti-tumor immunity may be the key to the prevention and treatment of cancer. Most traditional Chinese medicine have been proved to have good anti-tumor activity, and they have the advantages of better therapeutic effect and few side effects in the treatment of malignant tumors. An increasing number of studies are giving evidence that alkaloids extracted from traditional Chinese medicine possess a significant anticancer efficiency via regulating a variety of tumor-related genes, pathways and other mechanisms. This paper reviews the anti-tumor effect of alkaloids targeting tumor microenvironment, and further reveals its anti-tumor mechanism through the effects of alkaloids on different components in tumor microenvironment.

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Piperine inhibits colorectal cancer migration and invasion by regulating STAT3/Snail-mediated epithelial–mesenchymal transition

Cited by 38 publications

References 18 publications

Impact of Selected Signaling Proteins on SNAIL 1 and SNAIL 2 Expression in Ovarian Cancer Cell Lines in Relation to Cells’ Cisplatin Resistance and EMT Markers Level

Impact of Selected Signaling Proteins on SNAIL 1 and SNAIL 2 Expression in Ovarian Cancer Cell Lines in Relation to Cells’ Cisplatin Resistance and EMT Markers Level

Overview of the Anticancer Potential of the “King of Spices” Piper nigrum and Its Main Constituent Piperine

Tumor microenvironment: a prospective target of natural alkaloids for cancer treatment

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