Curcumin rescues breast cells from epithelial‑mesenchymal transition and invasion induced by anti‑miR‑34a

Abstract

Breast cancer is the most prevalent type of cancer among women worldwide and it is characterized by a high morbidity. Curcumin is a naturally occurring compound derived from the rhizome of Curcuma longa and is known to have antioxidant and anticarcinogenic properties. Emerging evidence has indicated that microRNAs (miRNAs or miRs) function as oncogenes or tumor suppressor genes to control invasion and migration. The aim of this study was to evaluate the effects of curcumin on genes implicated in epithelial-mesenchymal transition (EMT) and to examine the involvement of Rho-A in the migration and invasion of MCF-10F and MDA-MB-231 breast cell lines. Furthermore, to the best of our knowledge, this is the first study to examine the effects of curcumin on Rho-A and on genes involved in EMT, such as Axl, Slug and CD24 in order to determine whether the compound is able to prevent migration and invasion by targeting miRNAs as a regulator of such genes. Specifically, we focused on miR-34a which acts as a tumor suppressor gene in human breast cell lines. The present study demonstrated that the Axl, Slug and CD24 genes were implicated in EMT, and Rho-A was also involved in the migration and invasion of MCF-10F and MDA-MB-231 cell lines. Curcumin also acted upon the miRNA as a regulator of genes implicated in EMT and upon Rho-A as well, affecting the migration and invasion of the cells. This occurred independently of their estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) receptors in the non-malignant MCF-10F and malignant MDA-MB-231 breast cell lines, which are both negative for such receptors.

Role of Pirin, an Oxidative Stress Sensor Protein, in Epithelial Carcinogenesis

“…Interestingly, we found that Pirin levels are increased by HPV16 E6 and E7 oncoproteins in infected cervical cancer cells, unlike HPV-negative cells [50]. Moreover, curcumin, a common food additive and well-known antioxidant agent [53,54], has been reported to interfere with EMT in HeLa cells (HPV-18) and breast cancer cell lines [55][56][57]. Notably, we demonstrated that curcumin decreases Pirin levels as well as reduces EMT and cell migration suggesting a novel Pirin-dependent mechanism wherein curcumin rescues cervical cancer cells from EMT [58].…”

Role of Pirin, an Oxidative Stress Sensor Protein, in Epithelial Carcinogenesis

“…Interestingly, we found that Pirin levels are increased by HPV16 E6 and E7 oncoproteins in infected cervical cancer cells, unlike HPV-negative cells [ 63 ]. Moreover, curcumin, a common food additive and well-known antioxidant agent [ 65 , 66 ], has been reported to interfere with EMT in HeLa cells (HPV-18) and breast cancer cell lines [ 67 , 68 , 69 ]. Notably, we demonstrated that curcumin decreases Pirin levels and reduces EMT and cell migration, suggesting a novel Pirin-dependent mechanism wherein curcumin rescues cervical cancer cells from EMT [ 70 ].…”

Participation of MicroRNAs in the Treatment of Cancer with Phytochemicals

“…Curcumin and genistein exert their anti-cancer effects through modulating miR-34 levels in breast cancer and head and neck cancer, respectively [ 45 , 133 ] ( Figure 2 and Table 4 ). EMT is negatively controlled by miR-34 that targets EMT-triggering factors, such as zinc finger E-box binding homeobox 1 (ZEB1) and snail family transcriptional repressor 1 (SNAI1) in breast cancer [ 237 ].…”

“…EMT is negatively controlled by miR-34 that targets EMT-triggering factors, such as zinc finger E-box binding homeobox 1 (ZEB1) and snail family transcriptional repressor 1 (SNAI1) in breast cancer [ 237 ]. Curcumin elevates miR-34 levels, and EMT-related genes repressed by curcumin is restored by miR-34 knockdown, indicating that miR-34 mediates the effects of curcumin on EMT [ 133 ].…”