Abstract
Curcumin (CUR) and berberine (BBR) are renowned natural compounds that exhibit potent anticancer activities through distinct molecular mechanisms. However, the anticancer capacity of either CUR or BBR is limited. This prompted us to investigate the chemopreventive potential of co-treatment of CUR and BBR against breast cancers. The results showed that CUR and BBR in combination synergistically inhibited the growth of both MCF-7 and MDA-MB-231 breast cancer cells than the compounds used alone. Further study confirmed that synergistic anti-breast cancer activities of co-treatment of these two compounds was through inducing more apoptosis and autophagic cell death (ACD). The co-treatment-induced apoptosis was caspase-dependent and through activating ERK pathways. Our data also demonstrated that co-treatment of CUR and BBR strongly up-regulated phosphorylation of JNK and Beclin1, and decreased phosphorylated Bcl-2. Inhibition of JNK by SP600125 markedly decreased LC3-II and Beclin1, restored phosphorylated Bcl-2, and reduced the cytotoxicity induced by the two compounds in combination. These results strongly suggested that JNK/Bcl-2/Beclin1 pathway played a key role in the induction of ACD in breast cancer cells by co-treatment of CUR and BBR. This study provides an insight into the potential application of curcumin and berberine in combination for the chemoprevention and treatment of breast cancers.
Highlights
Breast cancer, the leading cause of cancer death among females, has ranked the second among all new cancer cases in the world, and has been growing by 2.0% per year[1]
Endocrine therapies target estrogen and increase the survival rate of patients with breast cancer, drug-resistance is usually the main reason to limit the efficacy of breast cancer therapy[6]
We demonstrated that co-treatment of CUR and BBR exhibited synergistic chemopreventive effects through inducing caspase-dependent apoptosis and autophagic cell death via activation of Extracellular signal-regulated kinase (ERK) and JNK/Beclin1/Bcl-2 signaling pathways, respectively, in MCF-7 and MDA-MB-231 breast cancer cell lines
Summary
The leading cause of cancer death among females, has ranked the second among all new cancer cases in the world, and has been growing by 2.0% per year[1]. Each of the compounds could enhance the sensitivity of cancer cells to conventional chemotherapeutic drugs[24,25] Considering their distinct chemical properties, promising anticancer activities, multiple targets, low toxicity, and rich resources, it is intriguing to investigate whether combination of two renowned natural compounds CUR and BBR could exert synergistic chemopreventive effects, in on breast cancer cells. We demonstrated that co-treatment of CUR and BBR exhibited synergistic chemopreventive effects through inducing caspase-dependent apoptosis and autophagic cell death via activation of ERK and JNK/Beclin1/Bcl-2 signaling pathways, respectively, in MCF-7 and MDA-MB-231 breast cancer cell lines. Our results suggested that combination of curcumin and berberine could be a promising approach for breast cancer chemoprevention
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