Dose-dependent effects of berberine on cell cycle pause and apoptosis in Balb/c 3T3 cells

Yang, In‐Hyoung; Chou, Chih-Chung; Yung, Benjamin Yat‐Ming

doi:10.1007/bf00178709

Cited by 35 publications

(34 citation statements)

References 15 publications

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“…Instead, both nucleus and cytoplasm become steadily more Xuorescent as the concentration of berberine added to the cultures increases above 50 M. Although detailed washout experiments have not been conducted, the cytoplasm and nucleus appear to have aYnity for berberine, as the Xow cytometry data was obtained from cells that had been washed out of berberine (resuspended in PBS) for approximately 15 min. This conclusion is supported by previous studies reporting staining of nuclei and cytoplasm by berberine [20,24,25]. We interpret these results as indicating that most berberine preferentially accumulates in mitochondria at lower concentrations (<50 M), but these binding sites become saturated at higher concentrations (>50 M), and berberine subsequently accumulates in the cytoplasm and nucleus.…”

Section: Discussionsupporting

confidence: 91%

“…Interestingly, an earlier study also correlated diVerences in berberine concentration and distribution with the responses of Balb/c 3T3 cells. In that study, 100 M berberine was mostly located in the cytoplasm and induced a G2/M arrest (similar to our results), while 200 M was concentrated in the nucleus and triggered apoptosis [25]. Together, these data suggest that the following multiphase model of action can be proposed: low concentrations of berberine are selectively accumulated by mitochondria, resulting in altered mitochondrial function, a reduction in ATP synthesis, activation of a G1 energy checkpoint, and consequently a slowing or arrest of cell proliferation.…”

Section: Discussionsupporting

confidence: 90%

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Different concentrations of berberine result in distinct cellular localization patterns and cell cycle effects in a melanoma cell line

Serafim

Oliveira

Sardão

et al. 2007

Cancer Chemother Pharmacol

118

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Purpose Natural products represent a rich reservoir of potential small molecule inhibitors exhibiting antiproliferative and tumoricidal properties. An example is the isoquinoline alkaloid berberine, which is found in plants such as goldenseal (Hydrastis canadensis). Studies have shown that berberine is able to trigger apoptosis in diVerent malignant cell lines, and can also lead to cell cycle arrest at sub-apoptotic doses. A particularly interesting feature of berberine is the fact that it is a Xuorescent molecule, and its uptake and distribution in cells can be studied by Xow cytometry and epiXuorescence microscopy. To test the relationships between berberine uptake, distribution and cellular eVect in melanoma cells, K1735-M2 mouse and WM793 human melanoma cells were treated with diVerent concentrations of berberine, and alterations in cell cycle progression, DNA synthesis, cell proliferation, and cell death measured. Methods Cell proliferation was measured by sulforhodamine B assays, cell death by Xow cytometry, berberine uptake and distribution by laser scanning confocal microscopy and Xow cytometry, cell cycle progression by Xow cytometry, and DNA synthesis, M-phase, and mitochondrial eVects by immunolabeling and epiXuorescence microscopy methods. Results In these melanoma cell lines, berberine at low doses (12.5-50 M) is concentrated in mitochondria and promotes G1 arrest. In contrast, higher doses (over 50 M) result in cytoplasmic and nuclear berberine accumulation, and G2 arrest. DNA synthesis is not markedly aVected by low doses of berberine, but 100 M is strongly inhibitory. Even at 100 M, berberine inhibits cell growth with relatively little induction of apoptosis. Conclusion Berberine displays multiphasic eVects in these malignant cell lines, which are correlated with the concentration and intracellular distribution of this alkaloid. These results help explain some of the conXicting information in the literature regarding the eVects of berberine, and suggest that its use in clinical development may be more as a cytostatic agent than a cytotoxic compound.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 90%

Different concentrations of berberine result in distinct cellular localization patterns and cell cycle effects in a melanoma cell line

Serafim

Oliveira

Sardão

et al. 2007

Cancer Chemother Pharmacol

118

View full text Add to dashboard Cite

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“…It is interesting that similar effect was observed in OC2 cells. Berberine-induced cell cycle arrest at G2/M phase and apoptosis in Balb/c 3T3 cells (Yang et al, 1996), however, the dose of berberine used (268-537 µM) was much higher than we used (32 µM) in this study. In this study, berberine treatment did not induce G2/M arrest and berberine attenuated Paclitaxel-induced response was not the result of berberine-elicited cycle arrest effect (Figure 4).…”

Section: Discussionmentioning

confidence: 57%

Berberine modulates expression of mdr1 gene product and the responses of digestive track cancer cells to Paclitaxel

Lin

Liu

et al. 1999

Br J Cancer

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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 n M –10 μ M ) treatment for 24 h induced cytotoxicity in OC2, SC-M1 and COLO 205 cells in a dose-dependent manner. Pretreatment of cells with 32 μ M 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. © 1999 Cancer Research Campaign

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“…The number of 20,000 events was acquired and the cells were properly gated for analysis for apoptosis. For cell cycle analysis, treated the cells with different concentration of berberine (20,40, or 80 µM) for 24 h. Then, cells were harvested, washed with PBS, fixed with cold (4˚C) 70% ethanol, washed with 50% and 30% ethanol, and PBS finally; Stained with 1 ml of 20 mg/ml PI containing RNase (1 mg/ml) in PBS for 30 min followed by FACS for cycle analysis. Each assay was done in triplicate.…”

Section: Flow Cytometric Analysis For Apoptosis and Cell Cycle Arrestmentioning

confidence: 99%

“…Sub-confluent HCT116 cells were seeded in 6-well plates, then treated with different concentrations of berberine (20,40 or 80 µM) and DMSO was introduced as vehicle control for 12 and 24 h. For total protein level assay, cells were washed with cold PBS (4˚C) and lysed in 300 µl lysis buffer. For nucleus fraction protein extraction, the protein was harvested as per kit introductions (#78833, Pierce Biotechnology, Inc., Rockford, IL, USA).…”

Section: Flow Cytometric Analysis For Apoptosis and Cell Cycle Arrestmentioning

confidence: 99%

Berberine inhibits the proliferation of colon cancer cells by inactivating Wnt/β-catenin signaling

2012

Int J Oncol

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Abstract. Colon cancer is one of the most common malignancies, mainly initiated by the abnormal activation of Wnt/β-catenin signaling. In this study, we investigated the proliferation inhibitory effect of berberine on colon cancer cells and the molecular basis underlying this effect. With the viability, apoptosis and cell cycle assay, we demonstrated that berberine can inhibit proliferation, induce apoptosis and cell cycle arrest in colon cancer cells. In in vivo investigation, we demonstrated that berberine can prevent the colon cancer formation initiated by dimethylhydrazine (DMH) and dextran sodium sulfate (DSS) in rats. We employed Western blotting, reverse transcription and polymerase chain reaction, special antagonist, overexpression and knockdown techniques to dissect the possible molecular mechanisms mediating the function of berberine. We found that the protein levels of β-catenin in the nucleus and cytoplasm were all reduced after treating the colon cancer cells with berberine, and this may not result from accelerating the degradation of β-catenin in the cytoplasm, but from inhibiting the mRNA expression of β-catenin. Our results indicate that berberine can be a potential chemoprevention and chemotherapy agent for human colon cancer by targeting Wnt/β-catenin signaling. IntroductionColon cancer, which causes considerable morbidity and mortality, is one of the most common malignancies and primarily initiated by the abnormal activation of Wnt/β-catenin signaling pathway (1). Although the treatment options have substantially increased and substantial benefits have been achieved for some patients, overall progress has been more modest than had been hoped (2). Thus, there is a great clinical need to explore new agents for the treatment of colon cancer. Herbal and natural products are valuable resources for anticancer drugs (3,4). Plant derived active components, their semi-synthetic and synthetic analogs have served as one of the major sources for anticancer drugs (5-8). Some plant derived compounds have been used for anticancer drugs for a few years (6), including vinblastine, vincristine, etoposide, teniposide, taxol, and camptothecin. Thus, natural products acted as a major role in cancer chemotherapy for the past decades (6).It has been reported that Chinese herb Coptis chinensis was a promising anticancer agent, of which the most active ingredient is berberine. In fact, berberine, an isoquinoline alkaline, has been used as anti-microbial, anti-diarrheal and anti-inflammatory agent for thousands of years (9). Because of its low toxicity and low cost, there has recently been considerable interest in the possible use of berberine in the treatment of human cancers. Several studies suggest that berberine can inhibit cell proliferation, also it has been reported that berberine can inhibit carcinogen, such as DMH, induced formation of aberrant crypt foci (ACF) in the rat colon, which is usually considered to be preneoplastic lesions of colon mucosa. However, the exact mechanism is not fully understood yet.We ...

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Dose-dependent effects of berberine on cell cycle pause and apoptosis in Balb/c 3T3 cells

Cited by 35 publications

References 15 publications

Different concentrations of berberine result in distinct cellular localization patterns and cell cycle effects in a melanoma cell line

Different concentrations of berberine result in distinct cellular localization patterns and cell cycle effects in a melanoma cell line

Berberine modulates expression of mdr1 gene product and the responses of digestive track cancer cells to Paclitaxel

Berberine inhibits the proliferation of colon cancer cells by inactivating Wnt/β-catenin signaling

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