Homosalate in Sunscreens and Cosmetics: Fuelling Breast Cancer Cells and Potential Treatment Resistance

Professor Philippa Darbre

Professor Philippa Darbre is Professor Emeritus (Oncology) in the School of Biological Sciences at the University of Reading. Her research interests centre on the molecular and cellular mechanisms of action of oestrogen and oestrogen-mimicking chemicals in human breast cancer cells, with a main focus on the ingredients contained in underarm cosmetics.

Q. Can you tell us what your recent research found and why this work is important?

Our recent work investigated whether four commonly used UV filters were present in breast tissue from 40 women who’d undergone mastectomies due to breast cancer diagnosis. We took measurements in three different locations across the breast to see if they were more heavily distributed at specific sites where breast cancer is most common. We found one or more UV filters were measurable in 84% of tissue samples—at least one breast region for 95% of the women. These UV filters have been shown to be oestrogenic, and their presence in human breast tissue suggests their potential to influence breast cancer development.

Q. The fact that they’re there and not easy to get rid of is annoying, but are they a cause for concern?

The problem is that UV filters are known to be endocrine disrupting chemicals or EDCs, which can mimic natural oestrogen found in our bodies. Lifetime exposure to oestrogen is an established risk factor for breast cancer.

 The UV filters BP-3 (Oxybenzone), OMC, 4-MBC, HS (Homosalate), and OCT are known EDCs and all possess oestrogenic properties. In separate studies, they have been shown to increase the growth of oestrogen-responsive human breast cancer cells when cultured under laboratory conditions (4, 5).

Furthermore, at levels we recently detected in human breast tissue, BP-3, OMC, and 4-MBC can increase proliferation, migration, and invasive properties of human breast cancer cells grown in cell culture (6, 7). This implies a potential for these UV filters to increase tumour spread. This is especially relevant for breast cancer, where tumour spread is the main cause of mortality.

Q. So, should we avoid using sunscreen?

The oestrogenic activity of UV filters and their identification in breast tissue suggests they may have the potential to influence breast cancer development, so their regular use –from the application of a personal care product such as moisturiser, or wearing impregnated clothing – should be avoided.

It’s best to avoid the sun when it’s hottest, cover up using a hat and cool long sleeves etc. However, if you cannot cover up, you could consider using an old-fashioned zinc oxide-based sunscreen

References 

1.       Ramos, S., Homem, V., Alves, A., & Santos, L. (2015). Advances in analytical methods and occurrence of organic UV-filters in the environment – A review. Science of the Total Environment, 526: 278-311.

2.       Janjua, N. R., Mogensen, B., Andersson, A., Petersen, J. H., Henriksen, M., Skakkebaek, N. E., & Wulf, H. C. (2004). Systemic absorption of the sunscreens benzophenone-3, octyl-methoxycinnamate, and 3-(4-methyl-benzilidene) camphor after whole-body topical application and reproductive hormone levels in humans. Journal of Investigative Dermatology, 123(1): 57-61.

3.       Barr, L., Alamer, M., & Darbre, P.D. (2018). Measurement of concentrations of four chemical UV filters in human breast tissue at serial locations across the breast. Journal of Applied Toxicology, 38(8): 1112-1120.

4.       Schlumpf, M., Schmid, P., Durrer, S., Conscience, M., Maerkel, K., Henseler, M., Gruetter, M., Herzog, I., Reolon, S., Ceccatelli, R., Faass, O., Stutz, E., Jarry, H., Wuttke, W., & Lichtensteiger, W. (2004). Endocrine activity and developmental toxicity of cosmetic UV filters–an update. Toxicology, 205(1-2): 113-22.

5.       Matsumoto, H., Adachi, S., & Suzuki, Y. (2005). Estrogenic activity of ultraviolet absorbers and the related compounds. Yakugaku Zasshi, 125(8): 643-52.

6.       Schlumpf, M., Cotton, B., Conscience, M., Haller, V., Steinmann, B., & Lichtensteiger, W. (2001). In vitro and in vivo estrogenicity of UV screens. Environmental Health Perspectives 109(3): 239-44.

7.       Alamer, M., & Darbre, P. D. (2018). Effects of exposure to six chemical ultraviolet filters commonly used in personal care products on motility of MCF-7 and MDA-MB-231 human breast cancer cells in vitro. Journal of Applied Toxicology 38(2): 148-159.

Further Reading

Homosalate demonstrated clear oestrogenic activity by activating oestrogen receptors, stimulating the proliferation of MCF-7 breast cancer cells, and upregulating oestrogen-responsive genes such as pS2 and progesterone receptor. It also promoted the release of extracellular vesicles (EVs) that enhanced migration ability and anchorage-independent growth of recipient tumour cells—a novel mechanism observed in vitro that indicates homosalate’s potential role in facilitating cancer cell communication and progression. These findings indicate that homosalate could potentially promote hormone-sensitive breast cancer growth and may contribute to more aggressive tumour behaviour through EV-mediated pathways.

Zhang, Y., Tu, L., Chen, J., & Zhou, L. (2024). Interference mechanisms of endocrine system and other systems of endocrine-disrupting chemicals in cosmetics – In vitro studies. International Journal of Endocrinology, 2024: 1-20.

Long-term exposure to homosalate significantly increased the migration and invasiveness of oestrogen-responsive MCF-7 and oestrogen-unresponsive MDA-MB-231 breast cancer cells, consistent with a possible role in promoting metastatic behaviour. Additionally, a reduction in E-cadherin levels, a key protein in cell adhesion, suggests homosalate may contribute to cancer progression.

Alamer, M., & Darbre, P. D. (2017). Effects of exposure to six chemical ultraviolet filters commonly used in personal care products on motility of MCF-7 and MDA-MB-231 human breast cancer cells in vitro. Journal of Applied Toxicology, 2018(38): 148-159.

Homosalate has a cytotoxic and genotoxic effect on MCF-7 human breast cancer cells, with exposure at certain concentrations significantly inducing micronucleus formation—an indicator of DNA damage. This research also concluded that homosalate can be considered a clastogenic substance, meaning it can cause chromosomes to break. This suggests a new mechanism by which homosalate might potentially contribute to breast cancer, as it demonstrates the ability to damage the genetic material of cells in addition to its previously established hormonal effects.

Yazar, S., & Ertekin, S. K. (2019). Assessment of the cytotoxicity and genotoxicity of homosalate in MCF-7. Journal of Cosmetic Dermatology, 2020(19): 246-252.

Homosalate has been observed to enhance the release of extracellular vesicles (EVs) from triple-negative breast cancer cells. These EVs possess anti-anoikis properties, meaning they prevent a form of programmed cell death that occurs when cells detach from their surroundings. This resistance to anoikis is a crucial characteristic of cancer progression and is known to be a factor in chemotherapy resistance. Homosalate may be involved in promoting a more aggressive cancer phenotype and could enhance the ability of breast cancer cells to resist ongoing treatment, based on laboratory findings.

Grisard, E., Lescure, A., Nevo, N., Corbe, M., Jouve, M., Lavieu, G., Joliot, A., Nery, E. D., Martin-Jaular, L., & Thery, C. (2021). Homosalate boosts the release of tumor-derived Extracellular Vesicles with anti-anoikis properties. Journal of Extracellular Vesicles, 11(7): e12242.