Berberine modulates expression of mdr1 gene product and the responses of digestive track cancer cells to Paclitaxel
Open accessAbstract
Berberine is the major constituent of Coptis chinese and is commonly used in Chinese herbal medicine to treat patients with gastrointestinal disorders. In this study, using flow cytometry, we have found that a 24-h berberine treatment up-regulated the multidrug-resistant transporter (pgp-170) expression in two oral (KB, OC2), two gastric (SC-M1, NUGC-3) and two colon (COLO 205, CT 26) cancer cell lines. Decreased retention of rhodamine 123 was observed in berberine-treated cells as compared to vehicle control. To examine whether the berberine modulated pgp-170 expression in cancer cells is associated with changes in drug resistance, we determined the cytotoxicity, cell cycle progression and cell morphology of Paclitaxel-treated cells. Paclitaxel (1 nM-10 microM) treatment for 24 h induced cytotoxicity in OC2, SC-M1 and COLO 205 cells in a dose-dependent manner. Pretreatment of cells with 32 microM berberine for 24 h prior to Paclitaxel treatment resulted in increased viability as compared to that of Paclitaxel-treated cells. In addition, Paclitaxel-induced apoptosis and/or G2/M arrest in these three cancer cell lines. Pretreatment of cells with berberine prior to Paclitaxel blocked the Paclitaxel-induced cell cycle responses and morphological changes. These results together suggest that berberine modulated the expression and function of pgp-170 that leads to reduced response to Paclitaxel in digestive track cancer cells.
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Berberine's effect on P-glycoprotein expression is tissue- and cell-line-dependent, with induction reported in certain contexts.
“Berberine’s effect on P-gp expression is, however, tissue- and cell-line-dependent, with induction reported in certain contexts [77,79].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [77]
The Results (Figure 1) report that berberine significantly increased P-glycoprotein (pgp-170) expression in five digestive-tract cancer cell lines, while expression in CT26 cells was much lower. This supports induction and variation among cell lines, but the paper does not establish that the effect is tissue-dependent beyond the digestive-tract cancer cells studied. (LLM, conf=0.82)
Experimental — accuracy not yet measuredBerberine is both a substrate and an inhibitor of P-glycoprotein and can increase the intestinal absorption of its substrates.
“Berberine is both a substrate and an inhibitor of P-glycoprotein (P-gp/MDR1), and can increase the intestinal absorption of its substrates [58,77,78]”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [77]
The Discussion (p. 421) says berberine increased P-glycoprotein expression and function in cancer cell lines, with reduced drug uptake in tumour cells. Neither those passages nor the additional searches for P-glycoprotein substrate, inhibition, and intestinal absorption establish that berberine is itself a substrate or inhibitor, or that it increases intestinal absorption of other substrates. Increased transporter function in tumour cells does not rule out a separate inhibitory effect under other conditions. (LLM, conf=0.76)
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“Berberine’s effect on P-gp expression is, however, tissue-and cell-line-dependent, with induction reported in certain contexts [77,79].”
- Authors
- Lin, H.-L., Liu, T.-Y., Wu, C.-W., & Chi, C.-W.
- Affiliations
- Taipei Veterans General Hospital (TW)
- Venue
- British Journal of Cancer
- Published
- 1999-09-10
- Volume
- 81
- Issue
- 3
- Pages
- 416-422
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC2362909
- OpenAlex
- W1965981994
- Cited by
- 100
- References
- 43
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 3 · 2015: 5 · 2014: 4 · 2013: 2 · 2012: 7
- FWCI
- 1.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Keywords
- berberine, P-glycoprotein, MDR1 gene, multidrug resistance, paclitaxel, digestive tract cancer, oral cancer cells, gastric cancer cells, colon cancer cells, apoptosis, G2/M cell cycle arrest, Coptis chinensis, herbal medicine
- MeSH terms
- Animals, Berberine, Carcinoma, Cell Cycle, Colonic Neoplasms, Fluorescent Dyes, Growth Inhibitors, Humans, Mouth Neoplasms, Stomach Neoplasms, Tumor Cells, Cultured, Apoptosis, Paclitaxel, Drug Resistance, Multiple, Drug Resistance, Neoplasm, Genes, MDR, Rhodamine 123, ATP Binding Cassette Transporter, Subfamily B, Member 1, Mice
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