Low-Dose Berberine Attenuates the Anti-Breast Cancer Activity of Chemotherapeutic Agents via Induction of Autophagy and Antioxidation

Abstract

Berberine (BBR), a major active component of Rhizoma coptidis, is one of the most promising agents for breast cancer adjuvant therapy. It is well accepted that BBR could exhibit remarkable anticancer efficacy with few side effects, and when treated with chemotherapeutic agents in combination, BBR could enhance the chemosensitivity of cancer cells. Our previous study reported that low-dose BBR (LDB) induced hormetic effect and attenuated the anticancer activity of chemotherapeutic agents. However, the underlying mechanisms are still unclear. In this study, we confirmed that LDB could promote cancer cell proliferation and antagonize the anti-breast cancer activities of chemotherapeutic agents. And the mechanisms were proved to be induction of autophagy and antioxidation by LDB. Our results showed that LDB could mildly induce reactive oxygen species, raise the level of autophagy by promoting the phosphorylation of adenosine monophosphate-activated protein kinase, and promote antioxidant enzymes expression through activating nuclear factor erythroid 2-related factor 2 in breast cancer cells. These findings revealed a potential negative impact of BBR on its adjuvant anti-breast cancer therapy, providing guidance for a safe and effective use of naturally originated medicines in the clinic.

Berberine as a Potential Anticancer Agent: A Comprehensive Review

“…It is a crystal yellow-colored isoquinoline alkaloid traditionally used in Chinese and Ayurvedic medicine. Recently, scientists have reported that Berberine possesses broad-spectrum therapeutic potential due to its action against various ailments such as diabetes, hypertension, depression, obesity, inflammation, and cancer [ 9 , 10 , 11 , 12 , 13 ]. Berberine sulfate and hydrochloride have also been considered efficient herbal treatments.…”

Integrated network pharmacology, bioinformatics, and molecular docking to explore the mechanisms of berberine regulating autophagy in breast cancer

“…[19] Similarly, Han et al showed that berberine can enhance the autophagy flux of MCF-7 and MDA-MB-231 cells. [20] However, a study demonstrated that berberine can reduce the number of autophagosomes in doxorubicin (ADR)-resistant MCF-7 cells (MCF-7/ADR) and reverse ADR resistance through PTEN/Akt/ mTOR signaling pathway. [21] Therefore, the role of AMGRBs in BRCA is complex, and more efforts are needed to reveal the potential molecular mechanism.…”

Berberine enhances autophagic flux by activating the Nrf2 signaling pathway in bovine endometrial epithelial cells to resist LPS‐induced apoptosis

“…Related to previous research, our study also discovered that BBR exerted an obvious anti‐apoptotic effect. In addition, recent research has demonstrated that a low dose of BBR activates autophagy in macrophages and cancer cells (Han et al, 2020). In the current research, we discovered that BBR strongly increased the lipidated level of LC3 in LPS‐stimulated BEECs in a dose‐dependent manner (Guo, Chen, et al, 2021).…”