Hormetic Effect of Berberine May Attenuate the Anticancer Activity of Chemotherapeutic Agents

Depending on Dosage

Rhizoma coptidis is a highly valued traditional Chinese medicine which has been widely applied in complementary and alternative medicines in China, Korea, India, Japan, and other Asian countries, especially for the treatment of dysentery, cancer, diabetes mellitus, and eczema, mostly used in formulas (Tang, et al., 2009). Berberine is one of the major active components of Rhizoma coptidis, which is an isoquinoline alkaloid with abundant pharmacological activities (Lu et al., 2012). 

As with all medicines, dosing is critical, none more so than with botanicals. Many botanicals are bi-directional that is, they may have opposite effects at low or at high dose. This is called hormesis and is the phenomenon of biphasic dose response characterized by exhibiting stimulatory or beneficial effects at low doses and inhibitory or toxic effects at high doses. Increasing numbers of chemicals of various types have been shown to induce apparent hormetic effect on cancer cells. However, the underlying significance and mechanisms remain to be elucidated. Berberine, one of the major active components of Rhizoma coptidis, has been manifested with notable anticancer activities. This study aims to investigate the hormetic effect of berberine and its influence on the anticancer activities of chemotherapeutic agents. 

Results published by Bao et al., (2015) demonstrated that berberine at low dose range (1.25 ~ 5 μM) promoted cell proliferation to 112% ~170% of the untreated control in various cancer cells, while berberine at high dose rage (10 ~ 80 μM) inhibited cell proliferation. Further, they observed that co-treatment with low dose berberine could significantly attenuate the anticancer activity of chemotherapeutic agents, including fluorouracil (5-FU), camptothecin (CPT), and paclitaxel (TAX). The hormetic effect and thereby the attenuated anticancer activity of chemotherapeutic drugs by berberine may attributable to the activated protective stress response in cancer cells triggered by berberine, as evidenced by up-regulated MAPK/ERK1/2 and PI3K/AKT signaling pathways.  These results provided important information to understand the potential side effects of hormesis, and suggested cautious application of natural compounds and relevant herbs in adjuvant treatment of cancer.

Berberine hydrochloride has been approved by China Food and Drug Administration as anti-dysentery drug for many years. In recent years, berberine has been demonstrated significant anticancer activities in various types of cancer (Jabbarzadeh Kaboli, et al., 2014; Ortiz, et al., 201. Moreover, berberine also showed synergistic anticancer effects in combination treatment of cancer with chemotherapeutic agents (Tong, et al., 2012) or radiotherapy (Zhang, et al., 2014). The encouraging results of studies suggest that berberine might have potential to be developed as an effective adjuvant anticancer agent.

It was shown that Coptidis Rhizoma extract and berberine may repress tumor progression by regressing abnormal cell proliferation, arresting cell cycle and inducing cell death. Studies also highlighted the actions of Coptidis Rhizoma extract and berberine in inhibiting tumor cell invasion and angiogenesis, which in turn abolish cancer metastasis. 

Some studies have also been conducted to reveal the potential effect of Coptidis Rhizoma extract and berberine in regulating tumor stromal microenvironment, as well as in preventing carcinogenesis. Most of the results have been demonstrated with in vivo models, but results of high-quality clinical trials are not yet available (Wang et al., 2015)

Source

Bao J, Huang B, Zou L, et al. PLoS One. 2015; 10(9): e0139298. doi:  10.1371/journal.pone.0139298

References

Jabbarzadeh Kaboli P, Rahmat A, Ismail P, Ling KH. Targets and mechanisms of berberine, a natural drug with potential to treat cancer with special focus on breast cancer. Eur J Pharmacol. 2014 Oct 5; 740():584-95.

Lu JJ, Bao JL, Chen XP, et al. Alkaloids isolated from natural herbs as the anticancer agents. Evid Based Complement Alternat Med. 2012; 2012():485042.

Ortiz LM, Lombardi P, Tillhon M, Scovassi AI. Berberine, an epiphany against cancer. Molecules. 2014 Aug 15; 19(8):12349-67.

Tong N, Zhang J, Chen Y, et al. Berberine sensitizes mutliple human cancer cells to the anticancer effects of doxorubicin in vitro. Oncol Lett. 2012 Jun; 3(6):1263-1267.

Tang J, Feng Y, Tsao S, et al. Berberine and Coptidis rhizoma as novel antineoplastic agents: a review of traditional use and biomedical investigations. J Ethnopharmacol. 2009 Oct 29; 126(1):5-17.

Wang N, Tan HY, Li L, Yuen MF, Feng Y. Berberine and Coptidis Rhizoma as potential anticancer agents: Recent updates and future perspectives. J Ethnopharmacol. 2015 Dec 24;176:35-48. doi: 10.1016/j.jep.2015.10.028.

Zhang Q, Zhang C, Yang X, et al. Berberine inhibits the expression of hypoxia induction factor-1alpha and increases the radiosensitivity of prostate cancer. Diagn Pathol. 2014 May 27; 9():98.

You can leave a response, or trackback from your own site.

Leave a Reply

You must be logged in to post a comment.