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Dimethyl Sulfoxide Suppresses Mouse 4T1 Breast Cancer Growth by Modulating Tumor-Associated Macrophage
Rui Deng1, Shi-Min Wang1, Tao Yin1
1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
Purpose:
The universal organic solvent dimethyl sulfoxide (DMSO) can be used as a differentiation inducer of many cancer cells and has been widely used as a solvent in laboratories. However, its effects on breast cancer cells are not well understood. The aim of this study is to investigate the effect and associated mechanisms of DMSO on mouse breast cancer.
Methods:
We applied DMSO to observe the effect on tumors in a mouse breast cancer model. Tumor-associated macrophages (TAMs) were tested by flow cytometry. Ex vivo tumor microenvironment was imitated by 4T1 cultured cell conditioned medium. Enzyme-linked immunosorbent assays were performed to detect interleukin (IL)-10 and IL-12 expression in medium. To investigate the cytotoxicity of DMSO on TAMs, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed.
Results:
We found that DMSO produced tumor retardation when injected into mouse peritoneal cavities in a certain concentration range (0.5-1.0 mg/g). Furthermore, as detected by flow cytometry, TAM subtypes were found to be transformed. We further imitated a tumor microenvironment in vitro by using 4T1 cultured cell conditioned medium. Similarly, by using low concentration DMSO (1.0%-2.0% v/v), TAMs were induced to polarize to the classically activated macrophage (M1-type) and inhibited from polarizing into the alternatively activated macrophage (M2-type) in the conditioned medium. IL-10 expression in tumors was reduced, while IL-12 was increased compared with the control. Furthermore, we reported that 2.0% (v/v) DMSO could lead to cytotoxicity in peritoneal macrophages after 48 hours in MTT assays.
Conclusion:
Our findings suggest that DMSO could exert antitumor effects in 4T1 cancer-bearing mice by reversing TAM orientation and polarization from M2- to M1-type TAMs. These data may provide novel insight into studying breast cancer immunotherapy.
Insights
Dimethyl sulfoxide (DMSO) demonstrated antitumor effects in mouse breast cancer models by reprogramming tumor-associated macrophages (TAMs) from M2 to M1 types. This suggests DMSO
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Dimethyl sulfoxide (DMSO) is a versatile organic solvent with known differentiation-inducing properties in various cancer cells.
- The specific impact of DMSO on breast cancer, particularly its mechanisms within the tumor microenvironment, remains incompletely understood.
- Tumor-associated macrophages (TAMs) play a critical role in breast cancer progression, with M2-type TAMs promoting tumor growth and M1-type TAMs exhibiting anti-tumor activity.
Purpose of the Study:
- To investigate the effects of DMSO on mouse breast cancer.
- To elucidate the underlying mechanisms by which DMSO influences the tumor microenvironment and breast cancer progression.
- To explore the potential of DMSO in modulating TAM polarization for therapeutic benefit.
Main Methods:
- DMSO was administered to a mouse breast cancer model to assess its impact on tumor growth.
- Flow cytometry was employed to analyze TAM subtypes and their polarization.
- In vitro experiments using conditioned medium from 4T1 cells mimicked the tumor microenvironment to study DMSO's effects on TAMs, alongside ELISA for cytokine analysis and MTT assays for cytotoxicity.
Main Results:
- DMSO administration resulted in tumor retardation within a specific concentration range (0.5-1.0 mg/g).
- DMSO treatment induced a shift in TAM subtypes and promoted M1-type polarization while inhibiting M2-type polarization in vitro.
- DMSO treatment led to decreased IL-10 and increased IL-12 expression, and exhibited cytotoxicity to peritoneal macrophages at 2.0% (v/v) after 48 hours.
Conclusions:
- DMSO exhibits antitumor effects in 4T1 cancer-bearing mice by reversing TAM polarization from M2 to M1 phenotypes.
- These findings offer a novel perspective on utilizing DMSO in breast cancer immunotherapy.
- Further research into DMSO's immunomodulatory properties could pave the way for new therapeutic strategies against breast cancer.
