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Does memantine show chemopreventive effect against mice 4T1 breast tumor model?
Gülşah Albayrak1, Elif Burcu Bali2, Funda Demirtaş Korkmaz3
1Department of Medical Biology, Faculty of Medicine, Ufuk University, Ankara, Turkey.
Background:
Cancer cells express higher levels of N-methyl-d-aspartate (NMDA) receptor. In this study, we aimed to use memantine as a potential blocker to inhibit the action of the NMDA receptor in cancer cells in vivo in order to investigate the potential chemopreventive effect of memantine in 4T1 tumor-bearing mice.
Methods:
To determine the potential chemopreventive effect of the compound, mice weights, tumor volumes, spleen IL-6, and tumor DNA methylation levels were investigated. A total of 26 Balb/c female mice were allocated into three groups. G1 (n = 6): tumor control group, G2 (n = 10): low dose (5mg/kg) memantine group, G3: high dose (10 mg/kg) memantine group (n = 10). G1 was inoculated with 4T1 cells without any memantine treatment. G2 and G3 were pretreated with 5 and 10 mg/kg memantine daily intraperitoneal (ip) injection (weekend off) for 10 days, respectively. Both G2 and G3 were subdivided into two groups as G2a (n = 4) and G3a (n = 4): tumor free groups and G2b (n = 6) and G3b (n = 6) tumor bearing groups.
Results:
Our results revealed that G3: high dose (10 mg/kg) memantine group, significantly (p = 0.0248) reduced the tumor volumes. We found that spleen IL-6 levels were significantly higher in memantine pretreated tumor free group p = 0.0204 ) We also found that high dose memantine treated tumor free group (G3a) has significantly lower genome-wide DNA methylation levels when compared to tumor control group (G1) p = 0.0012.
Discussion:
To the best of our knowledge, it is the first study that highlights a potential chemopreventive effect of memantine in vivo in the mouse 4T1 breast tumor model. But further investigations should be carried out to explore the chemopreventive mechanism of action for memantine in cancer.
Insights
High-dose memantine significantly reduced tumor volume in a mouse model, suggesting a potential chemopreventive effect. Further research is needed to understand memantine's cancer-fighting mechanisms.
Area of Science:
- Oncology
- Pharmacology
- Cancer Research
Background:
- Cancer cells exhibit elevated N-methyl-d-aspartate (NMDA) receptor expression.
- Memantine, an NMDA receptor blocker, was investigated for its chemopreventive potential in a 4T1 breast tumor mouse model.
Purpose of the Study:
- To evaluate the chemopreventive efficacy of memantine in vivo.
- To investigate the impact of memantine on tumor volume, spleen IL-6 levels, and DNA methylation in a 4T1 tumor model.
Main Methods:
- 26 Balb/c female mice were divided into tumor control and two memantine-treated groups (5mg/kg and 10mg/kg).
- Mice received daily intraperitoneal injections of memantine for 10 days.
- Tumor volumes, spleen IL-6, and genome-wide DNA methylation levels were analyzed.
Main Results:
- High-dose memantine (10 mg/kg) significantly reduced tumor volumes (p = 0.0248).
- Spleen IL-6 levels were significantly elevated in tumor-free mice treated with memantine (p = 0.0204).
- High-dose memantine treatment led to significantly lower genome-wide DNA methylation in tumor-free mice compared to controls (p = 0.0012).
Conclusions:
- This study is the first to suggest a potential in vivo chemopreventive effect of memantine in the 4T1 breast tumor model.
- Further research is warranted to elucidate the precise chemopreventive mechanisms of memantine in cancer treatment.
