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Page 6 of 13 Darbre. J Cancer Metastasis Treat 2019;5:58 I http://dx.doi.org/10.20517/2394-4722.2019.22

0.6 0.45
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0.25 0.15
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Figure 1. Increases in migration of MCF-7 human breast cancer cells following prior long-term exposure to several estrogen
disrupting chemicals contained in personal care products. Cell migration was measured in real-time as electrical impedance (cell
index) using xCELLigence technology with uncoated CIM-16 plates. Prior to the assay, cells had been grown. A: for 20 weeks with
–4
–5
–8
-5
no addition, 5 × 10 M methylparaben or 10 M n-butylparaben; B: for 23 weeks with no addition, 10 M 17b-estradiol, 10 M
-5
-4
octylmethoxycinnamate or 10 M benzophenone-3; C: for 32 weeks with or without 10 M aluminium chlorohydrate; D: for 9 weeks
-7
with or without 10 M triclosan. Conditions were as published for the parabens [30] , UV filters [35] , and aluminium chlorohydrate [42] .
Data for triclosan are unpublished personal results. UV: ultraviolet
differed between compounds and cell lines, with a noted loss of b-catenin only after long-term exposure to
OMC in the MCF-7 cells and an increase in MMP-2 after long-term exposure to OMC and 4-MBC in the
[35]
MDA-MB-231 cells .
Aluminium-based antiperspirant salts
Aluminium-based salts are used as antiperspirant in underarm cosmetics and dermal absorption of
[36]
aluminium from this use has been implicated in the development of breast cancer . Aluminium has
[38]
[37]
been measured in human breast tissue and breast cyst fluid at higher levels than in blood, and in
[39]
nipple aspirate fluid at higher levels in samples taken from women with than without breast cancer .
Aluminium, as well as several other metal ions, is a metalloestrogen and in the form of the antiperspirant
[40]
salts aluminium chloride or aluminium chlorohydrate it can displace radiolabeled 17b-estradiol from
estrogen receptors and regulate estrogen-responsive gene expression . However, aluminium has also been
[41]
shown to increase migratory and invasive activity of human breast cancer cells, although since effects were
[42]
found not only in estrogen-responsive MCF-7 but also estrogen-unresponsive MDA-MB-231 cells,
[43]
estrogen-independent mechanisms of action must also exist. The increased cell migration following long-
-4
term (32 weeks) treatment of MCF-7 cells with or without 10 M aluminium chlorohydrate are illustrated in
Figure 1C using xCELLigence technology (conditions as published in reference 42). More recent animal model
research has shown that non-transformed murine mammary gland (NMuMG) epithelial cells exposed
to aluminium chloride in vitro were transformed as judged by soft agar assay, and then when injected
[44]
into three mouse strains with increasing immunodeficiency formed tumours and metastasised in vivo .
Untreated cells formed tumours and metastasized to a limited extent in the highly immunodeficient and
natural killer (NK) cell deficient NSG mouse strain but not in the less permissive and NK cell competent
NOD SKID strain or nude strains. In contrast, NMuMG cells transformed in vitro by the aluminium
chloride formed large tumours and metastasized in all three mouse models .
[44]