Dendrosomal Nano-Curcumin Downregulates CCAT2 Expression Levels and Promotes Cell Cycle Arrest and Apoptosis in Tamoxifen-Resistant MCF-7 Cells

Moradi, Foruzan; Sadeghizadeh, Pouya; Najafi, Farhood; Sadeghizadeh, Majid

Dendrosomal Nano-Curcumin Downregulates CCAT2 Expression Levels and Promotes Cell Cycle Arrest and Apoptosis in Tamoxifen-Resistant MCF-7 Cells

Document Type : Article

Authors

¹ Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

² Department of Medical Sciences, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran

³ Department of Resin and Additives, Institute for Color Science and Technology

Abstract

Objectives: Tamoxifen (TAM) is routinely used for the treatment of estrogen-positive breast carcinoma. Approximately 40% of patients with metastatic breast cancer will develop resistance to TAM. TAM therapeutic failure has been a major challenge in the treatment of TAM-resistant breast cancer cells. Therefore, finding a way to eliminate TAM resistance is very valuable. Curcumin is a polyphenol extracted from the rhizomes of Curcuma longa and has extensive biological and pharmacological effects on many cancers. The purpose of this study was to look into the effects of dendrosomal nano-curcumin (DNC) on cell growth and apoptosis, as well as the effects of DNC on the expression levels of long non-coding RNA CCAT2 in TAM-resistant MCF-7 cells (TAM-R). Methods: TAM-R cells were created, and CCAT2 expression was evaluated in TAM-R compared to TAM-sensitive MCF-7 cells (TAM-S). Forty eighth hours after TAM-R treatment with 20 μM of DNC, Q-RT-PCR, and flow cytometry cell cycle and Annexin V-PI assays were performed. P-value < 0.05 was defined as statistical significance. Results: CCAT2 was significantly upregulated in TAM-R compared to TAM-S. DNC administration downregulated CCAT2 expression, and markedly suppressed cell cycle and induced apoptosis in TAM-R. Furthermore, DNC decreased the anti-apoptosis gene (BCL-2) and increased the apoptotic gene (BAX) expression levels respectively in TAM-R. Conclusion: DNC promoted cell cycle arrest and apoptosis, eventually by CCAT2 downregulation in TAM-R. However, the probable mechanisms of how DNC affects CCAT2 expression levels are unknown and need future studies.

Graphical Abstract