Breast Cancer: Current Research
Open Access

Berberine; Breast cancer; C-Jun phosphorylation; Fibronectin expression; Tumor progression; Metastasis

Introduction

Breast cancer remains a significant global health concern, with research efforts continuously seeking novel therapeutic approaches to combat its progression. One promising avenue involves investigating natural compounds with potential anti-cancer properties [1,2]. Berberine, a bioactive alkaloid derived from various plants, has garnered attention for its diverse pharmacological activities, including antiinflammatory and anti-tumor effects. Recent studies have highlighted its potential role in breast cancer management, with emerging evidence suggesting its ability to modulate critical signaling pathways implicated in cancer progression [3,4]. One such pathway involves the regulation of c-Jun phosphorylation and subsequent fibronectin expression, which plays a crucial role in tumor growth and metastasis. This article explores the latest research findings on how berberine targets this pathway to suppress fibronectin expression in breast cancer cells. The activation of c-Jun, a component of the AP-1 transcription factor complex, is closely associated with various cellular processes, including proliferation, differentiation, and apoptosis. Dysregulation of c-Jun signaling has been implicated in the pathogenesis of several cancers, including breast cancer. Phosphorylation of c-Jun at specific serine and threonine residues by upstream kinases, such as JNK (c-Jun N-terminal kinase), enhances its transcriptional activity, leading to the upregulation of target genes involved in tumor progression. Among these target genes, fibronectin—a glycoprotein that plays a crucial role in cell adhesion, migration, and invasion—has been identified as a key player in promoting breast cancer metastasis. Berberine has attracted considerable attention in cancer research due to its ability to modulate various signaling pathways involved in tumorigenesis [5,6]. Recent studies have elucidated its anti-cancer effects through multiple mechanisms, including induction of apoptosis, inhibition of cell proliferation, and suppression of angiogenesis. Moreover, berberine has been shown to exert its anti-metastatic effects by targeting molecules involved in cell adhesion and migration. One such molecule is fibronectin, whose expression is regulated, in part, by the c-Jun signaling pathway [7,8].

Methodology

Berberine-mediated inhibition of c-jun phosphorylation: A recent study conducted by researchers aimed to investigate the effect of berberine on c-Jun phosphorylation and its downstream target, fibronectin, in breast cancer cells. The findings revealed that treatment with berberine significantly inhibited the phosphorylation of c-Jun, thereby attenuating its transcriptional activity. This inhibition of c-Jun phosphorylation led to a subsequent decrease in the expression of fibronectin, ultimately impairing the migratory and invasive potential of breast cancer cells [9].

Discussion

The discovery of berberine’s ability to suppress c-Jun phosphorylation and fibronectin expression holds promising implications for breast cancer therapy. By targeting key signaling pathways involved in tumor progression and metastasis, berberine offers a potential therapeutic strategy for inhibiting breast cancer growth and metastatic spread. Furthermore, its natural origin and relatively low toxicity profile make it an attractive candidate for combination therapies or adjuvant treatments in breast cancer management [10].

Conclusion

While the study provides valuable insights into the anti-cancer mechanisms of berberine, further research is warranted to fully elucidate its therapeutic potential in breast cancer. Future studies should focus on investigating the efficacy of berberine in preclinical models and clinical trials, evaluating its safety profile, optimal dosage, and potential interactions with existing treatment modalities. Additionally, elucidating the precise molecular mechanisms underlying berberine’s effects on c-Jun phosphorylation and fibronectin expression will deepen our understanding of its anti-cancer properties. Overall, the findings underscore the importance of exploring natural compounds like berberine as promising candidates for the development of novel therapeutic approaches in breast cancer management.

References

1. Ikram M (1975) A review on the chemical and pharmacological aspects of genus Berberis. Planta Med 28: 353-358.

Indexed at, Google Scholar, Crossref

2. Liu Z, Liu Q, Xu B, Wu J, Guo C, et al. (2009) Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage. Mutat Res 662: 75-83.

Indexed at, Google Scholar, Crossref

3. Kim JB, Lee KM, Ko E, Han W, Lee JE, et al. (2008) Berberine inhibits growth of the breast cancer cell lines MCF-7 and MDA-MB-231. Planta Med 74: 39-42.

Indexed at, Google Scholar, Crossref

4. Kim S, Han J, Lee SK, Choi MY, Kim J, et al. (2012) Berberine suppresses the TPA-induced MMP-1 and MMP-9 expressions through the inhibition of PKC-alpha in breast cancer cells. J Surg Res 176: e21-e29.

Indexed at, Google Scholar, Crossref

5. Li X, Zhao SJ, Shi HL, Qiu SP, Xie JQ, et al. (2014) Berberine hydrochloride IL-8 dependently inhibits invasion and IL-8-independently promotes cell apoptosis in MDA-MB-231 cells. Oncol Rep 32: 2777-2788.

Indexed at, Google Scholar, Crossref

6. Ho YT, Yang JS, Li TC, Lin JJ, Lin JG, et al. (2009) Berberine suppresses in vitro migration and invasion of human SCC-4 tongue squamous cancer cells through the inhibitions of FAK, IKK, NF-kappaB, u-PA and MMP-2 and -9. Cancer Lett 279: 155-162.

Indexed at, Google Scholar, Crossref

7. Jabbarzadeh Kaboli P, Rahmat A, Ismail P, Ling KH (2014) Targets and mechanisms of berberine, a natural drug with potential to treat cancer with special focus on breast cancer. Eur J Pharmacol 740: 584-595.

Indexed at, Google Scholar, Crossref

8. Liang KW, Ting CT, Yin SC, Chen YT, Lin SJ, et al. (2006) Berberine suppresses MEK/ERK-dependent Egr-1 signaling pathway and inhibits vascular smooth muscle cell regrowth after in vitro mechanical injury. Biochem Pharmacol 71: 806-817.

Indexed at, Google Scholar, Crossref

9. Kim S, Oh SJ, Lee J, Han J, Jeon M, et al. (2013) Berberine suppresses TPA-induced fibronectin expression through the inhibition of VEGF secretion in breast cancer cells. Cell Physiol Biochem 32:1541-1550.

Indexed at, Google Scholar, Crossref

10. DeSantis C, Ma J, Bryan L, Jemal A (2013) Breast cancer statistics. CA Cancer J Clin 64: 52-62.

Indexed at, Google Scholar, Crossref