Phytochemicals, withaferin A and carnosol, overcome pancreatic cancer stem cells as c-Met inhibitors

Aliebrahimi, Shima; Kouhsari, Shideh Montasser; Arab, Seyed Shahriar; Shadboorestan, Amir; Ostad, Seyed Nasser

doi:10.1016/j.biopha.2018.07.055

Cited by 52 publications

(38 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Aliebrahimi et al (2018) investigated the ability of carnosol to act as an inhibitor of c-Met in pancreatic ductal adenocarcinoma (PDAC) cells [ 53 ]. c-Met is a receptor tyrosine kinase that is activated by the ligand hepatocyte growth factor (HGF); however, abnormal activation of c-Met is responsible for the low survival rate and high relapse rate of PDAC.…”

Section: Literature Reviewmentioning

confidence: 99%

“…Treatment of the human PDAC cell line AsPC-1 with 100 ng/mL of HGF induced cancer cell proliferation. Treatment with carnosol (0–60.5 µM) for 48 h significantly inhibited HGF-dependent growth with an IC 50 value of 14.56 µM [ 53 ]. Interestingly, the IC 50 value was higher in HGF-free media, indicating that the inhibitory effects of carnosol are tied to the HGF/c-Met signalling pathway.…”

Section: Literature Reviewmentioning

confidence: 99%

“…Flow cytometry analysis found carnosol, at its IC 50 concentration, to arrest AsPC-1 cells in the S phase of the cell cycle when compared to untreated cells. Furthermore, FITC-annexin V/propidium iodide staining and flow cytometry found 15 µM carnosol increased the proportion of cells in early apoptosis from 3% in the control group to 32% [ 53 ]. Additionally, 100 ng/mL HGF was found to promote 70% wound closure after 24 h in a scratch assay, but treatment with carnosol dose-dependently supressed this HGF-induced migration [ 53 ].…”

Section: Literature Reviewmentioning

confidence: 99%

“…Furthermore, FITC-annexin V/propidium iodide staining and flow cytometry found 15 µM carnosol increased the proportion of cells in early apoptosis from 3% in the control group to 32% [ 53 ]. Additionally, 100 ng/mL HGF was found to promote 70% wound closure after 24 h in a scratch assay, but treatment with carnosol dose-dependently supressed this HGF-induced migration [ 53 ]. With regards to HGF-mediated c-Met signalling, carnosol only inhibited phosphorylated c-Met and Akt at high concentrations (50 and 75 µM), while lower concentrations of carnosol (10 and 25 µM) increased phosphorylated c-Met [ 53 ].…”

Section: Literature Reviewmentioning

confidence: 99%

“…Additionally, 100 ng/mL HGF was found to promote 70% wound closure after 24 h in a scratch assay, but treatment with carnosol dose-dependently supressed this HGF-induced migration [ 53 ]. With regards to HGF-mediated c-Met signalling, carnosol only inhibited phosphorylated c-Met and Akt at high concentrations (50 and 75 µM), while lower concentrations of carnosol (10 and 25 µM) increased phosphorylated c-Met [ 53 ]. Moreover, carnosol (15 µM) reduced the self-renewal capacity of AsPC-1 cells, as determined by preventing the sphere growth of cells in suspension and decreasing colony formation in adherent cells from 48 colonies in the control to 18.…”

Section: Literature Reviewmentioning

confidence: 99%

See 4 more Smart Citations

Anticancer Properties of Carnosol: A Summary of In Vitro and In Vivo Evidence

et al. 2020

View full text Add to dashboard Cite

Cancer is characterized by unrestricted cell proliferation, inhibition of apoptosis, enhanced invasion and migration, and deregulation of signalling cascades. These properties lead to uncontrolled growth, enhanced survival, and the formation of tumours. Carnosol, a naturally occurring phyto-polyphenol (diterpene) found in rosemary, has been studied for its extensive antioxidant, anti-inflammatory, and anticancer effects. In cancer cells, carnosol has been demonstrated to inhibit cell proliferation and survival, reduce migration and invasion, and significantly enhance apoptosis. These anticancer effects of carnosol are mediated by the inhibition of several signalling molecules including extracellular signal-regulated kinase (ERK), p38, c-Jun N-terminal kinase (JNK), Akt, mechanistic target of rapamycin (mTOR) and cyclooxygenase-2 (COX-2). Additionally, carnosol prevents the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and promotes apoptosis, as indicated by increased levels of cleaved caspase-3, -8, -9, increased levels of the pro-apoptotic marker Bcl-2-associated X (BAX), and reduced levels of the anti-apoptotic marker B-cell lymphoma 2 (Bcl-2). The current review summarizes the existing in vitro and in vivo evidence examining the anticancer effects of carnosol across various tissues.

show abstract

Section: Literature Reviewmentioning

confidence: 99%

Section: Literature Reviewmentioning

confidence: 99%

Section: Literature Reviewmentioning

confidence: 99%

Section: Literature Reviewmentioning

confidence: 99%

Section: Literature Reviewmentioning

confidence: 99%

See 3 more Smart Citations

Anticancer Properties of Carnosol: A Summary of In Vitro and In Vivo Evidence

et al. 2020

View full text Add to dashboard Cite

show abstract

Preparation of Some New Pyrazolo[1,5‐a]pyrimidines and Evaluation of Their Antioxidant, Antibacterial (MIC and ZOI) Activities, and Cytotoxic Effect on MCF‐7 Cell Lines

Vahedi,

Asghari,

Tajbakhsh

et al. 2023

Chemistry & Biodiversity

View full text Add to dashboard Cite

This study aims to synthesize some novel pyrazolo[1,5‐a]pyrimidine derivatives, and investigate their biological activities. These compounds exhibited good to high antioxidant activities [2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging capabilities]. Among them, Ethyl 5‐(2‐ethoxy‐2‐oxoethyl)‐7‐hydroxy‐2‐methylpyrazolo[1,5‐a]pyrimidine‐3‐carboxylate (3h) showed the highest antioxidant activity [Half‐maximal Inhibitory Concentration (IC50)=15.34 μM] compared to ascorbic acid (IC50=13.53 μM) as a standard compound. Their antibacterial activities were investigated against two Gram‐positive bacteria (Bacillus subtilis, and Staphylococcus aureus) and two Gram‐negative bacteria (Pseudomonas aeruginosa, and Escherichia coli). The results showed that Ethyl 7‐hydroxy‐5‐phenylpyrazolo[1,5‐a]pyrimidine‐3‐carboxylate (3i) has the best antibacterial activity against Gram‐positive B. subtilis [Zone of Inhibition (ZOI)=23.0±1.4 mm, Minimum Inhibitory Concentration (MIC)=312 μM]. Also, the cytotoxicity of these compounds was assessed against breast cancer cell lines [human breast adenocarcinoma (MCF‐7)], which 7‐Hydroxy‐2‐methyl‐5‐phenylpyrazolo[1,5‐a]pyrimidine‐3‐carbonitrile (3f) displayed the most cytotoxicity (IC50=55.97 μg/mL), in contrast with Lapatinib (IC50=79.38 μg/mL) as a known drug.

show abstract

Carnosol suppresses RANKL‐induced osteoclastogenesis and attenuates titanium particles‐induced osteolysis

Lin

Liu

et al. 2020

Journal Cellular Physiology

View full text Add to dashboard Cite

Osteolysis is a common medical condition characterized by excessive activity of osteoclasts and bone resorption, leading to severe poor quality of life. It is essential to identify the medications that can effectively suppress the excessive differentiation and function of osteoclasts to prevent and reduce the osteolytic conditions. It has been reported that Carnosol (Car), isolated from rosemary and salvia, has antiinflammatory, antioxidative, and anticancer effects, but its activity on osteolysis has not been determined. In this study, we found that Car has a strong inhibitory effect on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation dose-dependently without any observable cytotoxicity. Moreover, Car can inhibit the RANKL-induced osteoclastogenesis and resorptive function via suppressing NFATc1, which is a result of affecting MAPK, NF-κB and Ca 2+ signaling pathways. Moreover, the particle-induced osteolysis mouse model confirmed that Car could be effective for the treatment of bone loss in vivo. Taken together, by suppressing the formation and function of RANKL-induced osteoclast, Car, may be a therapeutic supplementary in the prevention or the treatment of osteolysis.

show abstract

Phytochemicals, withaferin A and carnosol, overcome pancreatic cancer stem cells as c-Met inhibitors

Cited by 52 publications

References 39 publications

Anticancer Properties of Carnosol: A Summary of In Vitro and In Vivo Evidence

Anticancer Properties of Carnosol: A Summary of In Vitro and In Vivo Evidence

Preparation of Some New Pyrazolo[1,5‐a]pyrimidines and Evaluation of Their Antioxidant, Antibacterial (MIC and ZOI) Activities, and Cytotoxic Effect on MCF‐7 Cell Lines

Carnosol suppresses RANKL‐induced osteoclastogenesis and attenuates titanium particles‐induced osteolysis

Contact Info

Product

Resources

About