Tags

Type your tag names separated by a space and hit enter

Omega-3 DHA- and EPA-dopamine conjugates induce PPARγ-dependent breast cancer cell death through autophagy and apoptosis.
Biochim Biophys Acta 2015; 1850(11):2185-95BB

Abstract

BACKGROUND

The omega-3 docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may form conjugates with amines that have potential health benefits against common diseases including cancers. Here we synthesized DHA-dopamine (DHADA) and EPA-dopamine (EPADA) conjugates and studied their biological effects on different breast cancer cell lines.

METHODS AND RESULTS

MTT assays indicated that increasing concentrations of DHADA and EPADA significantly affected viability in MCF-7, SKBR3 and MDA-MB-231 breast cancer cells, whereas no effect was observed in MCF-10A non-tumorigenic epithelial breast cells. DHADA and EPADA enhanced Beclin-1 expression, as evidenced by immunoblotting, real-time-PCR and functional analyses. Chromatin Immunoprecipitation (ChIP) and Re-ChIP assays revealed that both compounds induced recruitment of Peroxisome-Proliferator-Activated-Receptor gamma (PPARγ) and RNA Polymerase-II at the Retinoic-X-Receptor binding region on Beclin-1 promoter. Moreover, both compounds enhanced autophagosome formation, evaluated by LC-3 and monodansylcadaverine labeling, that was prevented by the PPARγ antagonist GW9662, addressing the direct involvement of PPARγ. Noteworthy, long-term treatment with DHADA and EPADA caused the blockade of autophagic flux followed by apoptotic cell death as evidenced by PARP cleavage and DNA fragmentation in all breast cancer cells.

CONCLUSIONS

We have provided new insights into the molecular mechanism through which PPARγ, as a central molecule in the cross talk between autophagy and apoptosis, mediates DHADA- and EPADA-induced cell death in breast cancer cells.

GENERAL SIGNIFICANCE

Our findings suggest that omega-3 DHADA- and EPADA activation of PPARγ may assume biological relevance in setting novel adjuvant therapeutic interventions in breast carcinoma.

Authors+Show Affiliations

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy; Centro Sanitario, University of Calabria, Arcavacata di Rende (CS), Italy.Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy; Centro Sanitario, University of Calabria, Arcavacata di Rende (CS), Italy.Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy; Centro Sanitario, University of Calabria, Arcavacata di Rende (CS), Italy.Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy; Centro Sanitario, University of Calabria, Arcavacata di Rende (CS), Italy.Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy; Centro Sanitario, University of Calabria, Arcavacata di Rende (CS), Italy. Electronic address: daniela.bonofiglio@unical.it.Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy; Centro Sanitario, University of Calabria, Arcavacata di Rende (CS), Italy. Electronic address: sebastiano.ando@unical.it.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26272430

Citation

Rovito, Daniela, et al. "Omega-3 DHA- and EPA-dopamine Conjugates Induce PPARγ-dependent Breast Cancer Cell Death Through Autophagy and Apoptosis." Biochimica Et Biophysica Acta, vol. 1850, no. 11, 2015, pp. 2185-95.
Rovito D, Giordano C, Plastina P, et al. Omega-3 DHA- and EPA-dopamine conjugates induce PPARγ-dependent breast cancer cell death through autophagy and apoptosis. Biochim Biophys Acta. 2015;1850(11):2185-95.
Rovito, D., Giordano, C., Plastina, P., Barone, I., De Amicis, F., Mauro, L., ... Andò, S. (2015). Omega-3 DHA- and EPA-dopamine conjugates induce PPARγ-dependent breast cancer cell death through autophagy and apoptosis. Biochimica Et Biophysica Acta, 1850(11), pp. 2185-95. doi:10.1016/j.bbagen.2015.08.004.
Rovito D, et al. Omega-3 DHA- and EPA-dopamine Conjugates Induce PPARγ-dependent Breast Cancer Cell Death Through Autophagy and Apoptosis. Biochim Biophys Acta. 2015;1850(11):2185-95. PubMed PMID: 26272430.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Omega-3 DHA- and EPA-dopamine conjugates induce PPARγ-dependent breast cancer cell death through autophagy and apoptosis. AU - Rovito,Daniela, AU - Giordano,Cinzia, AU - Plastina,Pierluigi, AU - Barone,Ines, AU - De Amicis,Francesca, AU - Mauro,Loredana, AU - Rizza,Pietro, AU - Lanzino,Marilena, AU - Catalano,Stefania, AU - Bonofiglio,Daniela, AU - Andò,Sebastiano, Y1 - 2015/08/11/ PY - 2015/03/03/received PY - 2015/07/30/revised PY - 2015/08/09/accepted PY - 2015/8/15/entrez PY - 2015/8/15/pubmed PY - 2015/12/17/medline KW - Apoptosis KW - Autophagy KW - Beclin-1 KW - Breast cancer KW - Omega-3 polyunsaturated fatty acid conjugates KW - Peroxisome Proliferator-Activated Receptor gamma SP - 2185 EP - 95 JF - Biochimica et biophysica acta JO - Biochim. Biophys. Acta VL - 1850 IS - 11 N2 - BACKGROUND: The omega-3 docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may form conjugates with amines that have potential health benefits against common diseases including cancers. Here we synthesized DHA-dopamine (DHADA) and EPA-dopamine (EPADA) conjugates and studied their biological effects on different breast cancer cell lines. METHODS AND RESULTS: MTT assays indicated that increasing concentrations of DHADA and EPADA significantly affected viability in MCF-7, SKBR3 and MDA-MB-231 breast cancer cells, whereas no effect was observed in MCF-10A non-tumorigenic epithelial breast cells. DHADA and EPADA enhanced Beclin-1 expression, as evidenced by immunoblotting, real-time-PCR and functional analyses. Chromatin Immunoprecipitation (ChIP) and Re-ChIP assays revealed that both compounds induced recruitment of Peroxisome-Proliferator-Activated-Receptor gamma (PPARγ) and RNA Polymerase-II at the Retinoic-X-Receptor binding region on Beclin-1 promoter. Moreover, both compounds enhanced autophagosome formation, evaluated by LC-3 and monodansylcadaverine labeling, that was prevented by the PPARγ antagonist GW9662, addressing the direct involvement of PPARγ. Noteworthy, long-term treatment with DHADA and EPADA caused the blockade of autophagic flux followed by apoptotic cell death as evidenced by PARP cleavage and DNA fragmentation in all breast cancer cells. CONCLUSIONS: We have provided new insights into the molecular mechanism through which PPARγ, as a central molecule in the cross talk between autophagy and apoptosis, mediates DHADA- and EPADA-induced cell death in breast cancer cells. GENERAL SIGNIFICANCE: Our findings suggest that omega-3 DHADA- and EPADA activation of PPARγ may assume biological relevance in setting novel adjuvant therapeutic interventions in breast carcinoma. SN - 0006-3002 UR - https://www.unboundmedicine.com/medline/citation/26272430/Omega_3_DHA__and_EPA_dopamine_conjugates_induce_PPARγ_dependent_breast_cancer_cell_death_through_autophagy_and_apoptosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-4165(15)00213-5 DB - PRIME DP - Unbound Medicine ER -