Globally, cancer is a leading public health problem. The mortality rate due to cancer is rising throughout the world at an exponential rate. Thus, the development of robust strategies to mitigate cancer is essential. Plants are one of the richest sources of natural compounds and continue to provide novel remedies to mankind.
Natural products from plants represent a rich reservoir of potential chemical molecules exhibiting an impressive array of health benefits for various health problems. High dietary intake of natural products such as fruits, vegetables, dried fruits, and different spices have been found to reduce the risk of cancer.
One of such plant derivatives with biological properties is berberine. Berberine is an alkaloid, which possesses a broad range of therapeutic uses. Traditionally, it has been used in Ayurvedic, Chinese, Egyptian, and Iranian medicine system.
Different species of berberine-rich plants have versatile pharmacological properties such as antioxidant, anti-inflammatory, and immunomodulatory effects. Numerous studies have also assessed the potent anti-cancer activity of berberine and its derivatives.
Let us explore how this cancer-fighting alkaloid may help you:
- What is berberine?
- Sources of berberine
- Berberine and Cancer
- Ongoing trials of berberine in humans
1. What is berberine?
Berberine is a benzylisoquinoline quaternary alkaloid that belongs to the structural class of protoberberine. It is ubiquitously present in the roots, rhizome, and stem bark of several medicinal plant species.
2. Sources of berberine
The plants like tree turmeric, European barberry, goldenseal, phellodendron, orange grapes, prickly poppy, bacial skullcap root, goldthread and coptis are the major source of this phytochemical.
3. Berberine and Cancer
Recent advances demonstrate that berberine exhibits remarkable anti-cancer effects in a wide spectrum of cancers including, breast cancer, ovarian cancer, esophageal cancer, thyroid cancers, leukemia, multiple myeloma, nasopharyngeal carcinoma, and neuroblastoma. In human cancer cell lines, treatment with this alkaloid increased cell cycle arrest and death, coupled to an increased expression of apoptotic factors.
It exerts antineoplastic activities both in vitro and in vivo through different mechanisms. In studies using cancer cell lines, berberine has shown to:
- Induce cell cycle arrest and apoptosis of tumor cells
- Inhibit tumor migration and invasion by down-regulating the expression of metastasis-related proteins and signaling pathways
- Inhibit tumor cell proliferation by regulating cell cycle and cell autophagy
- Suppresses tumor angiogenesis
- Regulates tumor microenvironment
Therefore, through interference in tumorigenesis and multiple features of tumor development, berberine is extensively used in the prevention and treatment of tumors.
Along with these benefits, this potent alkaloid also known to interacts with microRNAs, regulates telomerase activity and exerts considerable positive effects on tumor immunotherapy.
Based on these potent anti-cancer competence of berberine, many novel derivatives have been synthesized to enhance the selectivity and efficiency of berberine. Heretofore,based on the results obtained on cancer cell lines, it can be said that barberine could be used as a potent agent for the management of cancer, stimulating further development of derivatives for drug-based cancer prevention and management.
The anti-cancer effect of berberine involves modulation of following signaling pathways:
- Mitogen-activated protein kinase (MAPK) signaling
- Phosphatidylinositol-3 kinase/AKT/mammalian target of rapamycin (PI3K/Akt/mTOR)
- Janus Kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3)
- Nuclear factor erythroid 2-related factor 2/hemeoxygenase-1 (Nrf2/HO-1)
4. Ongoing trials of berberine in humans
A randomized trial involved daily intake of 300 mg of berberine hydrochloride to verify whether berberine could reduce the occurrence of new colorectal adenomas in patients with a history of colorectal cancer.
A phase II clinical trial to assess the efficacy of berberine and gefitinib in patients with advanced NSCLC (non-small-cell lung cancer) and activating EGFR (epidermal growth factor receptor) mutations.
Berberine has attracted widespread attention because of its multiple pharmacological properties, low toxicity, and low cost. The substantial data obtained on cancer cells support an active role of berberine in inhibiting invasion of cancer cells. A combination of berberine with cancer therapies can found to be a great approach for managing cancer and can be used to synthesize several bioactive derivatives for designing new, selective, and powerful drugs.
With further in-depth analysis, berberine offers improved clinical safety and efficacy in cancer management. This may speed up its use in clinical practice as an ideal drug for immunotherapy and will eventually benefit cancer patients.