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Updated: May 22, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Berberine, a genotoxic alkaloid, induces ATM-Chk1 mediated G2 arrest in prostate cancer cells
Yu Wang1, Qiao Liu, Zhaojian Liu
1Ministry of Education Key Laboratory of Experimental Teratology and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, China.
Abstract:
Berberine has been shown to possess anti-tumor activity against a wide spectrum of cancer cells. It inhibits cancer cell proliferation by inducing cell cycle arrest, at G1 and/or G2/M, and apoptosis. While it has been documented that berberine induces G1 arrest by activating the p53-p21 cascade, it remains unclear what mechanism underlies the berberine-induced G2/M arrest, which is p53-independent. In this study, we tested the anti-proliferative effect of berberine on murine prostate cancer cell line RM-1 and characterized the underlying mechanisms. Berberine dose-dependently induced DNA double-strand breaks and apoptosis. At low concentrations, berberine was observed to induce G1 arrest, concomitant with the activation of p53-p21 cascade. Upon exposure to berberine at a higher concentration (50 μM) for 24h, cells exhibited G2/M arrest. Pharmacological inhibition of ATM by KU55933, or Chk1 by UCN-01, could efficiently abrogate the G2/M arrest in berberine-treated cells. Downregulation of Chk1 by RNA interference also abolished the G2/M arrest caused by berberine, confirming the role of Chk1 in the pathway leading to G2/M arrest. Abrogation of G2/M arrest by ATM inhibition forced more cells to undergo apoptosis in response to berberine treatment. Chk1 inhibition by UCN-01, on the other hand, rendered cells more sensitive to berberine only when p53 was inhibited. Our results suggest that combined administration of berberine and caffeine, or other ATM inhibitor, may accelerate the killing of cancer cells.
Insights
Berberine halts cancer cell growth by causing DNA damage and apoptosis. This study reveals berberine induces G2/M arrest via the ATM-Chk1 pathway, suggesting combination therapies for enhanced anti-cancer effects.
Area of Science:
- Pharmacology
- Molecular Biology
- Cancer Research
Background:
- Berberine exhibits anti-tumor properties across various cancer types.
- Berberine induces G1 arrest via p53-p21, but G2/M arrest mechanisms are unclear.
- Prostate cancer remains a significant health concern, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the anti-proliferative effects of berberine on RM-1 murine prostate cancer cells.
- To elucidate the molecular mechanisms underlying berberine-induced G2/M cell cycle arrest.
- To explore potential combination therapies for enhanced cancer cell killing.
Main Methods:
- Cell proliferation assays on RM-1 cells treated with berberine.
- Analysis of DNA damage, apoptosis, and cell cycle progression.
- Pharmacological inhibition and RNA interference targeting ATM and Chk1 pathways.
Main Results:
- Berberine induced dose-dependent DNA double-strand breaks, apoptosis, and cell cycle arrest (G1 and G2/M).
- Berberine-induced G2/M arrest is p53-independent and mediated by the ATM-Chk1 pathway.
- Inhibition of ATM or Chk1 abrogated berberine-induced G2/M arrest, increasing apoptosis.
Conclusions:
- Berberine effectively inhibits prostate cancer cell proliferation through DNA damage and apoptosis induction.
- The ATM-Chk1 pathway is crucial for berberine-induced G2/M arrest.
- Combined berberine with ATM inhibitors (e.g., caffeine) may enhance anti-cancer efficacy.
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