Abstract
Oestrogen receptor (ER)-positive breast cancer is one of the common forms of breast cancer affecting women worldwide. ER-positive breast cancer patients are subjected to anti-oestrogen therapy such as selective oestrogen receptor modulator (SERM) and aromatase inhibitors (AIs). Recently, the emergence of resistance to anti-oestrogen treatment is under intensive focus. The different mechanisms postulated to explain the occurrence of resistance in ER-positive breast cancer treatment include the loss of ER function and the crosstalk between signalling pathways in cancer cells. Recent literature highlighted that the cholesterol biosynthesis pathway acts as a novel mechanism underlying resistance to oestrogen deprivation. The present study aimed to highlight the role of cholesterol biosynthesis in anti-oestrogen treatment resistance, putatively suggesting an alternative plant-based treatment using andrographolide from Andrographis paniculata. The hypolipidaemic effect of andrographolide can be utilised to prevent the resistance in the treatment of ER-positive breast cancer contributed by cholesterol biosynthesis.
Highlights
Oestrogen-receptor (ER)-positive breast cancer can be treated with various forms of anti-hormone treatment
We analysed the potential of andrographolide, the bioactive compound of Andrographis paniculata in reducing the production of cholesterol that is required for the growth and resistance of cancer cells
A recent study published by The Institute of Cancer Research (ICR) [18] stated that ER-positive breast cancers produce a molecule made from cholesterol, termed as 25-hydroxycholesterol
Summary
Oestrogen-receptor (ER)-positive breast cancer can be treated with various forms of anti-hormone treatment. ER-positive breast tumours, which acquire this form of resistance, continue to exhibit ER expression despite exposure to anti-oestrogen These cancer cells might operate based on either of the two modes, tamoxifen-non-responsive or tamoxifendependent proliferation [12]. A recent study published by The Institute of Cancer Research (ICR) [18] stated that ER-positive breast cancers produce a molecule made from cholesterol, termed as 25-hydroxycholesterol It mimics oestrogen and promotes the growth of cancer cells despite the lack of oestrogen during the anti-hormone treatment. Instead of using statin as a part of the ER-positive treatment, we would like to propose the use of andrographolide, a natural product to target the cholesterol biosynthesis pathway to manage the occurrence of breast cancer resistance to hormone therapy. Note: The dashed arrows represent the multi-step transitions in the mevalonate pathway 12 www.mjms.usm.my
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