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Moderate intensity static magnetic fields affect mitotic spindles and increase the antitumor efficacy of 5-FU and
Yan Luo1, Xinmiao Ji1, Juanjuan Liu2
1High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui 230031, PR China.
Abstract:
Microtubules are the fundamental components in mitotic spindle, which plays essential roles in cell division. It was well known that purified microtubules could be affected by static magnetic fields (SMFs) in vitro because of the diamagnetic anisotropy of tubulin. However, whether these effects lead to cell division defects was unknown. Here we find that 1T SMFs induce abnormal mitotic spindles and increase mitotic index. Synchronization experiments show that SMFs delay cell exit from mitosis and cause mitotic arrest. These mimic the cellular effects of a microtubule-targeting drug Paclitaxel (Taxol), which is frequently used in combination with 5-Fluorouracil (5-FU) and Cisplatin in cancer treatment. Using four different human cancer cell lines, HeLa, HCT116, CNE-2Z and MCF7, we find that SMFs increase the antitumor efficacy of 5-FU or 5-FU/Taxol, but not Cisplatin, which indicates that the SMF-induced combinational effects with chemodrugs are drug-specific. Our study not only reveals the effect of SMFs on microtubules to cause abnormal mitotic spindles and delay cells exit from mitosis, but also implies the potential applications of SMFs in combination with chemotherapy drugs 5-FU or 5-FU/Taxol, but not with Cisplatin in cancer treatment.
Insights
Static magnetic fields (SMFs) disrupt cell division by affecting microtubules, leading to abnormal mitotic spindles. These fields enhance the effectiveness of certain chemotherapy drugs like 5-Fluorouracil (5-FU) in cancer treatment.
Area of Science:
- Cell Biology
- Oncology
- Biophysics
Background:
- Microtubules are crucial for cell division, forming the mitotic spindle.
- Static magnetic fields (SMFs) are known to affect purified microtubules in vitro.
- The impact of SMFs on cell division and their therapeutic potential remained unclear.
Purpose of the Study:
- To investigate the effects of 1 Tesla SMFs on cell division.
- To determine if SMFs induce defects in mitotic spindles.
- To explore the potential of SMFs in combination with chemotherapy for cancer treatment.
Main Methods:
- Utilized synchronization experiments to analyze cell cycle progression.
- Exposed four human cancer cell lines (HeLa, HCT116, CNE-2Z, MCF7) to SMFs.
- Assessed the combined effects of SMFs with chemotherapy drugs: 5-Fluorouracil (5-FU), Paclitaxel (Taxol), and Cisplatin.
Main Results:
- 1T SMFs induced abnormal mitotic spindles and increased the mitotic index.
- SMFs delayed cell exit from mitosis, causing mitotic arrest, similar to Taxol.
- SMFs enhanced the antitumor efficacy of 5-FU and 5-FU/Taxol combinations, but not Cisplatin.
Conclusions:
- SMFs disrupt microtubule dynamics, leading to abnormal mitotic spindles and delayed mitotic exit.
- SMFs show potential for enhancing the efficacy of specific chemotherapy regimens (5-FU, 5-FU/Taxol) in cancer treatment.
- The drug-specific interactions highlight the need for tailored combination therapies.
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