Characterising the Molecular and Functional Phenotypes of RAW264.7 Macrophages under Cannabidiol (CBD) and Tamoxifen Treatment

Abstract

Breast cancer remains a major global health concern. While standard treatments like Tamoxifen have been effective, limitations such as side effects and drug resistance necessitate the exploration of novel therapeutic approaches. Cannabidiol, a non- psychoactive cannabinoid, has emerged as a promising agent with potential anti- cancer properties. Macrophages, key players in the tumour microenvironment, can be polarised into M1 and M2 phenotypes. M1 macrophages exhibit potent anti-tumour activity, while M2 macrophages promote tumour growth and metastasis. Understanding how to modulate macrophage polarisation could offer new therapeutic avenues. This study aimed to investigate the synergistic effects of CBD and Tamoxifen on breast cancer cell growth and macrophage activation. By utilising MCF7 breast cancer cells and RAW264.7 macrophages, the study sought to elucidate the underlying molecular mechanisms that contribute to these compounds’ anticancer and immunomodulatory effects. The present study employed a combination of functional assays and proteomic analysis to explore the mechanisms underlying both macrophage polarisation and the effects of CBD and Tamoxifen on MCF7 and RAW264.7 cells. The results demonstrate that CBD and Tamoxifen, particularly in combination, can induce M1 macrophage polarisation. This is characterised by increased nitric oxide production and upregulation of protein pathways associated with inflammation, including those involved in cytokine production and cellular metabolic processes, which collectively support the anti-tumour functions of M1 macrophages. Additionally, these treatments enhanced RAW264.7 macrophage phagocytosis of MCF7 breast cancer cells. The findings of this study suggest that CBD and Tamoxifen may synergistically modulate the tumour microenvironment. By promoting M1 macrophage polarisation and inhibiting tumour cell growth, this combination therapy holds promise as a novel approach for breast cancer treatment. Further research is warranted to fully elucidate the underlying molecular mechanisms and to explore the clinical potential of CBD and Tamoxifen in breast cancer therapy.