Correction to: Role of mitochondria and cardiolipins in growth inhibition of breast cancer cells by retinoic acid

In the original publication of this article [1], the images of Figs. 4 and 5 were exchanged and the legends of the two figures did not correspond due to a typesetting error.

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Induction of Apoptosis and Autophagy by Ternary Copper Complex Towards Breast Cancer Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666210726132543 ◽

2021 ◽

Vol 21 ◽

Author(s):

Zheng Yang Lee ◽

Chee Hong Leong ◽

Krystal U Ling Lim ◽

Christopher Chun Sing Wong ◽

Pornwasu Pongtheerawan ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Growth Inhibition ◽

Cancer Cells ◽

Copper Complex ◽

Breast Cancer Cells ◽

Caspase 3 ◽

Caspase 9 ◽

Mcf 7

Background: Copper complex has been gaining much attention in anticancer research as targeted agent since cancer cells uptake more copper than non-cancerous cells. Our group has synthesised a ternary copper complex which is composed of 1,10-phenanthroline and tyrosine [Cu(phen)(L-tyr)Cl].3H20. These two payloads are designed to cleave DNA and inhibit protein degradation system (proteasome) concurrently in cancer cells, making this copper complex a dual-target compound. Objective: Current study was carried out to investigate the mode of cell death and role of autophagy induced by [Cu(phen)(L-tyr)Cl].3H20 in MCF-7 and MDA-MB-231 breast cancer cells. Methods: Growth inhibition of [Cu(phen)(L-tyr)Cl].3H20 towards MDA-MB-231 and human non-cancerous MCF10A breast cells was determined by MTT assay. Annexin-V-FITC/PI and cell cycle analysis were evaluated by flow cytometry. The expression of p53, Bax, caspase-9, caspase-7, caspase-3 and LC3 were determined using western blot analysis. The cells were then co-treated with hydroxychloroquine to ascertain the role of autophagy induced by [Cu(phen)(L-tyr)Cl].3H20. Results: [Cu(phen)(L-tyr)Cl].3H20 inhibited the growth of cancer cells dose-dependently with less toxicity towards MCF10A cells. Additionally, [Cu(phen)(L-tyr)Cl].3H20 induced apoptosis and cell cycle arrest towards MCF-7 and MDA-MB-231 breast cancer cells possibly via regulation of p53, Bax, caspase-9, caspase-3 and capase-7. The expression of LC3II was upregulated in both cancer cell lines upon treatment with [Cu(phen)(L-tyr) Cl].3H20, indicating the induction of autophagy. Co-treatment with autophagy inhibitor hydroxychloroquine significantly enhanced growth inhibition of both cell lines, suggesting that the autophagy induced by [Cu(phen)(L-tyr) Cl].3H20 in both breast cancer cells was promoting cell survival. Conclusion: [Cu(phen)(L-tyr)Cl].3H20 holds great potential to be developed for breast cancer treatment.

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Inhibition of trans-retinoic acid-resistant human breast cancer cell growth by retinoid X receptor-selective retinoids.

Molecular and Cellular Biology ◽

10.1128/mcb.17.11.6598 ◽

1997 ◽

Vol 17 (11) ◽

pp. 6598-6608 ◽

Cited By ~ 61

Author(s):

Q Wu ◽

M I Dawson ◽

Y Zheng ◽

P D Hobbs ◽

A Agadir ◽

...

Keyword(s):

Breast Cancer ◽

Retinoic Acid ◽

Growth Inhibition ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cells ◽

Breast Cancer Cell Lines ◽

Trans Retinoic Acid

All-trans-retinoic acid (trans-RA) and other retinoids exert anticancer effects through two types of retinoid receptors, the RA receptors (RARs) and retinoid X receptors (RXRs). Previous studies demonstrated that the growth-inhibitory effects of trans-RA and related retinoids are impaired in certain estrogen-independent breast cancer cell lines due to their lower levels of RAR alpha and RARbeta. In this study, we evaluated several synthetic retinoids for their ability to induce growth inhibition and apoptosis in both trans-RA-sensitive and trans-RA-resistant breast cancer cell lines. Our results demonstrate that RXR-selective retinoids, particularly in combination with RAR-selective retinoids, could significantly induce RARbeta and inhibit the growth and induce the apoptosis of trans-RA-resistant, RAR alpha-deficient MDA-MB-231 cells but had low activity against trans-RA-sensitive ZR-75-1 cells that express high levels of RAR alpha. Using gel retardation and transient transfection assays, we found that the effects of RXR-selective retinoids on MDA-MB-231 cells were most likely mediated by RXR-nur77 heterodimers that bound to the RA response element in the RARbeta promoter and activated the RARbeta promoter in response to RXR-selective retinoids. In contrast, growth inhibition by RAR-selective retinoids in trans-RA-sensitive, RAR alpha-expressing cells most probably occurred through RXR-RAR alpha heterodimers that also bound to and activated the RARbeta promoter. In MDA-MB-231 clones stably expressing RAR alpha, both RARbeta induction and growth inhibition by RXR-selective retinoids were suppressed, while the effects of RAR-selective retinoids were enhanced. Together, our results demonstrate that activation of RXR can inhibit the growth of trans-RA-resistant MDA-MB-231 breast cancer cells and suggest that low cellular RAR alpha may regulate the signaling switch from RAR-mediated to RXR-mediated growth inhibition in breast cancer cells.

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