Differential anti-tumor activities of curcumin against Ras- and Src-activated human adenocarcinoma cells

Ono, Misaki; Higuchi, Takako; Takeshima, Mikako; Chen, Chen; Nakano, Susumu

doi:10.1016/j.bbrc.2013.05.071

Cited by 23 publications

(15 citation statements)

References 30 publications

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“…Potentially acting through a similar mechanism, curcumin arrests Ras-transfected HAG-1 human adenocarcinoma cells in G 2 /M phase by inducing expression of extracellular signal-regulated kinase 1/2 and Bax, and reducing expression of Bcl-xL. These results suggest that curcumin may be a potent therapy against Ras-overexpressing cancer (59). Preclinical studies in animals, and ultimately clinical trials, are required to clarify the therapeutic effect of curcumin in Ras-induced cancer.…”

Section: Targets Of Curcumin In Ras Signalingmentioning

confidence: 96%

Molecular targets of curcumin in breast cancer (Review)

et al. 2018

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Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of Curcuma longa. For centuries, curcumin has been used in medicinal preparations and as a food colorant. In recent years, extensive in vitro and in vivo studies have suggested that curcumin possesses activity against cancer, viral infection, arthritis, amyloid aggregation, oxidation and inflammation. Curcumin exerts anticancer effects primarily by activating apoptotic pathways in cancer cells and inhibiting pro-cancer processes, including inflammation, angiogenesis and metastasis. Curcumin targets numerous signaling pathways associated with cancer therapy, including pathways mediated by p53, Ras, phosphatidylinositol-3-kinase, protein kinase B, Wnt-β catenin and mammalian target of rapamycin. Clinical studies have demonstrated that curcumin alone or combined with other drugs exhibits promising anticancer activity in patients with breast cancer without adverse effects. In the present review, the chemistry and bioavailability of curcumin and its molecular targets in breast cancer are discussed. Future research directions are discussed to further understand this promising natural product.

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Section: Targets Of Curcumin In Ras Signalingmentioning

confidence: 96%

Molecular targets of curcumin in breast cancer (Review)

et al. 2018

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“…The anti-proliferative effect of lycopene on these breast cancer cells was assessed by WST assay, as described previously. (30) Briefly, 100 lL suspension of cells was seeded into each well of a 96-well plate (BD Falcon, Franklin Lakes, NJ, USA) at a density of 2000 cells per well. This inoculation density was determined by the growth curves so that nontreated cells did not reach confluency for up to 7 days, without medium change.…”

Section: Determination Of Growth Inhibition and Apoptosis Assessmentmentioning

confidence: 99%

“…Immunoprecipitation and western blot analysis were performed as described previously. (30) Equal amounts of proteins or immunoprecipitated target proteins were resolved by 4-15% SDS-PAGE (Bio Rad, Hercules, CA, USA) and electrotransferred onto a polyvinylidene difluoride membrane (GE Healthcare, Piscataway, NJ, USA). Non-specific binding sites were blocked by incubating the membranes in blocking buffer (Nacalai Tesque, Kyoto, Japan) at room temperature for 30 min.…”

Section: Determination Of Growth Inhibition and Apoptosis Assessmentmentioning

confidence: 99%

Anti‐proliferative and apoptosis‐inducing activity of lycopene against three subtypes of human breast cancer cell lines

et al. 2014

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Although lycopene, a major carotenoid component of tomatoes, has been suggested to attenuate the risk of breast cancer, the underlying preventive mechanism remains to be determined. Moreover, it is not known whether there are any differences in lycopene activity among different subtypes of human breast cancer cells. Using ER/PR positive MCF-7, HER2-positive SK-BR-3 and triple-negative MDA-MB-468 cell lines, we investigated the cellular and molecular mechanism of the anticancer activity of lycopene. Lycopene treatment for 168 consecutive hours exhibited a time-dependent and dose-dependent anti-proliferative activity against these cell lines by arresting the cell cycle at the G0/G1 phase at physiologically achievable concentrations found in human plasma. The greatest growth inhibition was observed in MDA-MB-468 where the sub-G0/G1 apoptotic population was significantly increased, with demonstrable cleavage of PARP. Lycopene induced strong and sustained activation of the ERK1/2, with concomitant cyclin D1 suppression and p21 upregulation in these three cell lines. In triple negative cells, lycopene inhibited the phosphorylation of Akt and its downstream molecule mTOR, followed by subsequent upregulation of proapoptotic Bax without affecting anti-apoptotic Bcl-xL. Taken together, these data indicate that the predominant anticancer activity of lycopene in MDA-MB-468 cells suggests a potential role of lycopene for the prevention of triple negative breast cancer.

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“…Our work therefore suggests that JAK2 upregulation is responsible for the abnormal activation of STATs in the polycystic kidney. On the contrary, it has been suggested that STAT3 activation can be JAK2-indepenenent and instead Src-mediated in ADPKD 29 ; interestingly curcumin has been shown to inhibit Src-mediated signalling 35,36 . Therefore, future work using selective kinase inhibitors is needed to decipher the pathways that participate in disease development.…”

Section: Discussionmentioning

confidence: 99%

JAK2 is highly expressed by cyst-lining cells and regulates cystogenesis

Patera

Cudzuch-Mardy

Huang

et al. 2018

Preprint

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Autosomal dominant polycystic kidney disease (ADPKD) arises primarily due to Pkd1 mutations and is characterised by increased kidney epithelial proliferation. The Janus Kinase and Signal Transducers and Activators of Transcription (JAK-STAT) is a proliferation regulating pathway implicated in ADPKD. Curcumin, an anti-inflammatory phytochemical, has been shown to limit murine cystogenesis possibly via JAK-STAT. However, the mechanisms employed by curcumin to inhibit JAK-STAT are uncertain. We treated ADPKD-derived renal epithelial cells with curcumin at different concentrations over 9 days and studied their growth in organotypic cystforming assays. Curcumin potently blocked cystic growth in human and mouse renal epithelial cells without requiring any additional cell types, suggesting a direct effect on kidney epithelial cells. The level of tyrosine phosphorylated-STAT3 was reduced within 1 hour of curcumin treatment in a dose-dependent manner. While total STAT3 protein levels remained unaltered, suggesting that curcumin reduces phosphorylation of STAT3 possibly via JAK2, a tyrosine kinase upstream of STAT3. Mechanistically, curcumin caused JAK2 to move into an insoluble fraction, without causing JAK2 proteosomal-degradation. Instead curcumin led to JAK2 to accumulate into aggresomes, which are known depots for inactivated enzymes. We studied JAK2 expression in kidneys of the Pkd1 nl/nl mice, which spontaneously develop progressive ADPKD. JAK2 was highly expressed in cyst-lining renal epithelial cells at 5 and 10 weeks of age, suggesting a potential role in ADPKD pathophysiology. Collectively, these data suggest that curcumin reduces STAT3 signalling and cystic growth by inactivating JAK2, thus selective JAK2 inhibition may be of therapeutic benefit in ADPKD.

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Differential anti-tumor activities of curcumin against Ras- and Src-activated human adenocarcinoma cells

Cited by 23 publications

References 30 publications

Molecular targets of curcumin in breast cancer (Review)

Molecular targets of curcumin in breast cancer (Review)

Anti‐proliferative and apoptosis‐inducing activity of lycopene against three subtypes of human breast cancer cell lines

JAK2 is highly expressed by cyst-lining cells and regulates cystogenesis

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