High doses of hydroxytyrosol induce apoptosis in papillary and follicular thyroid cancer cells

Toteda, Giuseppina; Lupinacci, Simona; Vizza, Donatella; Bonofiglio, Renzo; Perri, Enzo; Bonofiglio, Martina; Lofaro, Danilo; Russa, Antonella La; Leone, Francesca; Gigliotti, Paolo; Cifarelli, Rosa Anna; Perri, Anna

doi:10.1007/s40618-016-0537-2

Cited by 55 publications

(42 citation statements)

References 35 publications

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“…In this context, a simultaneous modulatory effect of HT against several potential targets is a highly desirable attribute. Our results also suggest a cell cycle modulatory effect of HT with dose-dependent inhibition of cell cycle regulatory molecules cyclin D1 and cyclin E. Inhibition of cyclin D1 seems to be an important part of HT and there are reports of cyclin D1 down-regulation by HT in few other cancer models as well, such as colon cancer Caco-2 (28), breast cancer MCF-7 (29)/MDA-MB-231 (10) and thyroid cancer cells (30). Similarly, there is evidence for HT-mediated up-regulation of p21 and p27 (17), confirming our current findings.…”

Section: Discussionmentioning

confidence: 99%

Hydroxytyrosol Induces Apoptosis and Cell Cycle Arrest and Suppresses Multiple Oncogenic Signaling Pathways in Prostate Cancer Cells

Zubair

Bhardwaj

Ahmad

et al. 2017

Nutrition and Cancer

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Scope: Hydroxytyrosol (HT), a polyphenol from olives, is a potential anticancer agent. This study was designed to evaluate the anticancer activity of HT against prostate cancer cells, and the mechanism thereof. Methods and Results: Treatment of LNCaP and C4–2 prostate cancer cells with HT resulted in a dose-dependent inhibition of proliferation. This was in contrast to HT’s ineffectiveness against normal prostate epithelial cells RWPE1 and PWLE2, suggesting cancer cells-specific effect. HT induced G1/S cell cycle arrest, with inhibition of cyclins D1/E and cdk2/4, and induction of inhibitory p21/p27. HT also induced apoptosis, as confirmed by flow cytometry, caspase activation, PARP cleavage and BAX/Bcl-2 ratio. It inhibited the phosphorylation of Akt / STAT3, and induced cytoplasmic retention of NF-κB, which may explain its observed effects. Finally, HT inhibited AR expression and the secretion of AR-responsive prostate-specific antigen. Conclusion: Castration-resistant prostate cancers retain AR signaling and are often marked by activated Akt, NF-κB and STAT3 signaling. Our results establish a pleiotropic activity of HT against these oncogenic signaling pathways. Combined with its non-toxic effects against normal cells, our results support further testing of HT for prostate cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Hydroxytyrosol Induces Apoptosis and Cell Cycle Arrest and Suppresses Multiple Oncogenic Signaling Pathways in Prostate Cancer Cells

Zubair

Bhardwaj

Ahmad

et al. 2017

Nutrition and Cancer

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“…[20,21,22] The consumption of olive oil exerts a protective effect in reducing firstly CRC risk and many other types of cancer risk, including prostatic cancer, the breast ones. [23,24] This property has been referred to its content of monounsatured fats, principally oleic acid. [19] However olive oil is a functional and complex food and it contains several minor bioactive compounds including tocopherols, squalene, alcohols and many polyphenols such as oleuropein, hydroxytyrosol and tyrosol which represent approximately the 80% of olive oil's phenolic content.…”

Section: Olive Oil Polyphenolsmentioning

confidence: 99%

Mediterranean diet and colorectal cancer: A systematic review

et al. 2017

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Colorectal cancer is the third most common cancer worldwide, especially in developed countries where an estimated 60% of all cases occur. There is evidence of a higher risk for CRC in Western society, where people tend to eat more red and processed meat than those living along the Mediterranean coast, who have a decreased overall cancer mortality, which is correlated to their eating habits, such as Mediterranean diet. The aim of this review was to evaluate the correlation between three components of the Mediterranean diet (olive oil, red wine, and tomatoes) and incidence and progression of colorectal cancer. As such, we conducted a literature search using keywords "colorectal cancer," "dietary pattern," "Mediterranean diet," "olive oil," "protective effects," "resveratrol," and "lycopene." Olive oil polyphenols, red wine resveratrol, and tomato lycopene showed several characteristics in vitro that interfere with molecular cancer pathways. At the same time, many clinical studies have reported an association of these components with a reduction in cancer initiation and progression. More clinical studies are needed to identify the precise dose and administration of single agents or their combination to produce a coadjutant treatment to those already applied in chemoprevention and oncologic treatment.

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“…Hydroxytyrosol significantly enhanced caspase‐9 thyroid cancer cells. In contrast, Hydroxytyrosol did not activate caspase‐8 in treated thyroid cancer cells …”

Section: Tgf/smad Mediated Signaling In Thyroid Cancermentioning

confidence: 86%

Signaling cascades in thyroid cancer: Increasing the armory of archers to hit bullseye

Rashid

Mansoor

Tabassum

et al. 2018

J of Cellular Biochemistry

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Thyroid cancer is a multifaceted and therapeutically challenging disease and rapidly accumulating experimentally verified findings have considerably improve our understanding of the molecular mechanisms which underlie its development. Substantial fraction of information has been added into existing landscape of molecular oncology and we have started to develop a sharper understanding of the underlying mechanisms of thyroid cancer. Wealth of information demystified different intracellular signaling cascades which are frequently deregulated in thyroid cancer. In vitro assays and xenografted mice based studies have helped us to identify drug targets and different synthetic and natural products are currently being tested to effectively treat thyroid cancer. Cabozantinib and vandetanib have been approved to treat medullary thyroid cancer (MTC) and two agents (lenvatinib and sorafenib) are also being used to treat radioactive-iodine refractory differentiated thyroid cancer. This review comprehensively summarizes most recent advancements in our knowledge related to dysregulated intracellular signaling cascades in thyroid cancer and how different proteins can be therapeutically exploited. (1) We discuss how loss of TRAIL mediated apoptosis occurred in thyroid cancer cells and how different strategies can be used to restore apoptosis in resistant cancer cells; (2) We provide detailed account of seemingly opposite roles of NOTCH signaling in thyroid cancers; (3) TGF/SMAD mediated signaling also needs detailed research because of context dependent role in thyroid cancer. Researchers have only begun to scratch the surface of how TGF signaling works in thyroid cancer and metastasis; and (4) Role of SHH signaling in thyroid cancer stem cells is also well appreciated and targeting of SHH pathway will be an important aspect in treatment of thyroid cancer. Better concepts and improved knowledge will be helpful for clinicians in getting a step closer to individualized medicine.

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High doses of hydroxytyrosol induce apoptosis in papillary and follicular thyroid cancer cells

Cited by 55 publications

References 35 publications

Hydroxytyrosol Induces Apoptosis and Cell Cycle Arrest and Suppresses Multiple Oncogenic Signaling Pathways in Prostate Cancer Cells

Hydroxytyrosol Induces Apoptosis and Cell Cycle Arrest and Suppresses Multiple Oncogenic Signaling Pathways in Prostate Cancer Cells

Mediterranean diet and colorectal cancer: A systematic review

Signaling cascades in thyroid cancer: Increasing the armory of archers to hit bullseye

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