Flavonoid-induced autophagy in hormone sensitive breast cancer cells

Brunelli, Elisa; Pinton, Giulia; Bellini, Paolo; Minassi, Alberto; Appendino, Giovanni; Moro, Laura

doi:10.1016/j.fitote.2009.04.002

Cited by 14 publications

(12 citation statements)

References 18 publications

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“…Growth inhibition within 24 h was more pronounced after treatment with 6-PN than after treatment with the two control HDACi at similar or even higher concentrations. Our results are in line with previous reports that showed induction of cytotoxicity at similar concentrations for the breast, renal and prostate cancer cell lines after single treatment [10,13,16,17,19].…”

Section: Discussionsupporting

confidence: 93%

“…Inhibition of multi drug resistance-associated transporters P-glycoprotein and MRP1 by 8-PN was demonstrated [15]. Furthermore, 8-PN directly inhibits activation of PI(3)K/Akt pathway in MCF-7 cells in vitro [16]. 6-PN and 8-PN exhibit pronounced antiproliferative effects on PC-3 and DU145 human prostate cancer cell lines in vitro [17] in the absence of caspase-3 activation and typical apoptotic morphological features [18].…”

Section: Introductionmentioning

confidence: 97%

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6- and 8-Prenylnaringenin, Novel Natural Histone Deacetylase Inhibitors Found in Hops, Exert Antitumor Activity on Melanoma Cells

Venturelli

Niessner

Sinnberg

et al. 2018

Cell Physiol Biochem

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Background/Aims: Prenylnaringenins are natural prenylflavonoids with anticancer properties. However, the underlying mechanisms have not been elucidated yet. Here we report a novel mode of action of 6- and 8-prenylnaringenin (PN) on human melanoma cells: Inhibition of cellular histone deacetylases (HDACs). Methods: We performed in silico and in vitro analyses using 6-PN or 8-PN to study a possible interaction of 6-PN or 8-PN with HDAC as well as Western blot and FACS analyses, real-time cell proliferation and cell viability assays to assess the impact of 6-PN and 8-PN on human metastatic melanoma cells. Results: In silico, 6-PN and 8-PN fit into the binding pocket of HDAC2, 4, 7 and 8, binding to the zinc ion of their catalytic center that is essential for enzymatic activity. In vitro, 100 µmol/L of 6-PN or 8-PN inhibited all 11 conserved human HDAC of class I, II and IV. In clinical oncology HDAC inhibitors are currently investigated as new anticancer compounds. In line, treatment of SK-MEL-28 cells with 6-PN or 8-PN induced a hyperacetylation of histone complex H3 within 2 h. Further, 6-PN or 8-PN mediated a prominent, dose-dependent reduction of cellular proliferation and viability of SK-MEL-28 and BLM melanoma cells. This effect was apoptosis-independent and accompanied by down-regulation of mTOR-specific pS6 protein via pERK/pP90 in SK-MEL-28 cells. Conclusion: The identification of a broad inhibitory capacity of 6-PN and 8-PN for HDAC enzymes with antiproliferative effects on melanoma cells opens the perspective for clinical application as novel anti-melanoma drugs and the usage as innovative lead structures for chemical modification to enhance pharmacology or inhibitory activities.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 97%

6- and 8-Prenylnaringenin, Novel Natural Histone Deacetylase Inhibitors Found in Hops, Exert Antitumor Activity on Melanoma Cells

Venturelli

Niessner

Sinnberg

et al. 2018

Cell Physiol Biochem

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“…We then used the obtained data to test 6‐PN and 8‐PN, which induce cell death in different cancer cell lines . Raman spectroscopy indicated that 6‐PN and 8‐PN did not induce either apoptosis nor necrosis, but did induce autophagy, as the PN‐incubated cells clustered in the same area as that of autophagic cells.…”

Section: Discussionmentioning

confidence: 99%

Raman spectroscopy as an analytical tool for melanoma research

et al. 2014

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SummaryBackground. Raman spectroscopy is an optical noninvasive screening technology that generates individual fingerprints of living cells by reflecting their molecular constitution. Aim. To discriminate melanoma cells from melanocytes, to identify drug-induced melanoma cell death stages (apoptosis, necrosis, autophagy) and to assess the susceptibility of melanoma cells to anticancer therapy. Methods. We used Raman spectroscopy on normal and melanoma cells, and on wild-type (WT) and mutant melanoma cells, to investigate whether the technique could distinguish between different types of cells, identify mutations and evaluate response to anticancer therapy. Results. Using the multivariate principal component analysis of the Raman spectra, melanocytes could be distinguished from melanoma cells, and WT melanoma cells could be distinguished from melanoma cells with BRAF or NRAS mutations. When we used the apoptosis inducer staurosporine, the necrosis inducer 3-bromopyruvate and the autophagy inducer resveratrol to induce cell death in SKMEL28 melanoma cells, Raman spectroscopy clearly distinguished between these three types of cell death, as confirmed by immunoblotting. Finally, the technique could discriminate between different melanoma cell lines according to their susceptibility to high-dose ascorbate. Conclusions. Raman spectroscopy is a powerful noninvasive tool to distinguish between melanocytes and melanoma cells, to analyze the specific type of cell death in melanoma cells, and to predict the susceptibility of melanoma cells to anticancer drugs.

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“…Cyclin D1, c-Myc, p21 and cyclin E-cdk2 are estrogen downstream targets [19]. Estradiol can increase cyclin D1 expression by stimulating cyclin D1 transcription via PI3-Kinase/Akt pathway [20]. The inhibitory effect of anti-estrogens on estrogen receptor activity leads to decreased cyclin D1 expression and dissociation of p21 and p27 from the cyclin D1-cdk4/6 complex then association with cyclinE-cdk2 complexes [21].…”

Section: Discussionmentioning

confidence: 99%

Induction of G1 cell cycle arrest and cyclin D1 down-regulation in response to pericarp extract of Baneh in human breast cancer T47D cells

et al. 2012

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Background and the purpose of the studyNatural products from plants have an important role in the development and production of new drugs mainly for cancer therapy. More recently, we have shown that the pericarp methanolic extract of Pistacia atlantica sub kurdica (with local name of Baneh) as a rich source of active biological components with high antioxidant and radical scavenging activities, has ability to cease proliferation and induce apoptosis in T47D human breast cancer cells. The present study aimed to clarify whether Baneh extract able to alter cell cycle progression of T47D cells or not.MethodsIn order to study the possible effect of Baneh extract on cell cycle of T47D cells, we evaluated cell cycle distribution and its regulatory proteins by flow cytometry and western blot analysis respectively.ResultsBaneh extract induced G0/G1 cell cycle arrest in conjunction with a marked decrease in expression of cyclin D1 and cdk4 that was strongly dependent on time of exposure. In parallel, Dox-treated T47D cells in early time points were accumulated on S phase, but after 48 h cell cycle progression was inhibited on G2/M. Dox promoted striking accumulation of cyclin B1 rapidly and enhanced cyclin A abundance.ConclusionTaken together, our results establish that the antitumor activity of the pericarp extract of Baneh partly is mediated via cell cycle arrest and downregulation of cyclin D1 and cdk4 expression. These findings warrant further evaluation regarding the mechanism(s) of action of this promising anticancer agent.

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Flavonoid-induced autophagy in hormone sensitive breast cancer cells

Cited by 14 publications

References 18 publications

6- and 8-Prenylnaringenin, Novel Natural Histone Deacetylase Inhibitors Found in Hops, Exert Antitumor Activity on Melanoma Cells

6- and 8-Prenylnaringenin, Novel Natural Histone Deacetylase Inhibitors Found in Hops, Exert Antitumor Activity on Melanoma Cells

Raman spectroscopy as an analytical tool for melanoma research

Induction of G1 cell cycle arrest and cyclin D1 down-regulation in response to pericarp extract of Baneh in human breast cancer T47D cells

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