Statins could be new treatment option in women with oestrogen receptor positive breast cancer

Kmietowicz, Zosia

doi:10.1136/bmj.i3108

Cited by 3 publications

(5 citation statements)

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“…Besides some minor discrepancies, several cohort studies or clinical trials showed accumulating evidence of the clinical benefits of statins for breast cancer patients, via nonlipid-lowering therapeutic effects, aka pleiotropic effects. [3][4][5] The involvement of glucoseand cholesterol-rich diets in the metabolic reprogramming of cells and the augmentation of the oncogenic process have also been reported. 6 Cholesterol plays vital metabolic and structural roles in the cells.…”

Section: Introductionmentioning

confidence: 97%

“…Therefore, the investigation of pleiotropic effects sometimes reveals novel applications of clinically proven medicines. Besides some minor discrepancies, several cohort studies or clinical trials showed accumulating evidence of the clinical benefits of statins for breast cancer patients, via nonlipid‐lowering therapeutic effects, aka pleiotropic effects . The involvement of glucose‐ and cholesterol‐rich diets in the metabolic reprogramming of cells and the augmentation of the oncogenic process have also been reported .…”

Section: Introductionmentioning

confidence: 99%

“…22 Additional proofs suggest that statins inhibit vital cellular functions in human embryonic stem cells via the suppression of stemness-related pathway. 22 Since it has been reported that the effects of statins vary by their type and the molecular signature of breast cancer, such as, hormone receptor positive or triple-negative breast cancers, 3,4 the impact of statins on cancer stem cells, as the initiating cells of cancer metastasis, recurrence, and drug resistance, has been less investigated. To the best of our knowledge, this is the first report to elucidate the impacts of simvastatin, atorvastatin, and lovastatin, as the three commonly used lipophilic statins with distinct chemical structures on EMT-related gene expression profiles in the triple-negative stem-like breast cancer cells and its functional impacts.…”

Section: Introductionmentioning

confidence: 99%

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Lipophilic statins antagonistically alter the major epithelial‐to‐mesenchymal transition signaling pathways in breast cancer stem–like cells via inhibition of the mevalonate pathway

Koohestanimobarhan

Salami

Imeni

et al. 2018

J of Cellular Biochemistry

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Resistance to therapies, recurrence, and metastasis remain challenging issues for breast cancer patients, particularly for triple-negative and breast cancer stem cells. The activation of the epithelial-to-mesenchymal transition (EMT) plays an indispensable role in the poor prognosis of those types. The accumulating proofs indicated that the mevalonate pathway crucially mediates a poor prognosis. Here, the effects of lipophilic 3-hydroxy-3-methyl-glutaryl-coenzyme A inhibitors, atorvastatin, lovastatin, and simvastatin, were investigated on expression and function of a selected profile of EMT-related genes in breast cancer stem-like cells. A nontoxic dose of statins (5 μM for 4 days) significantly (P < 0.05 and >2-fold change) altered expression of 50 of 71 studied genes with a shared cluster of 37 genes that are coding chief operator of signaling pathways in Hippo, Notch, Wnt, proliferation, invasion, angiogenesis, and cell death. They also significantly decreased the levels of Yap/Taz proteins and shifted the expression of vimentin/E-cadherin in favor of induction of differentiation. Statins significantly chemosensitized the treated cells to doxorubicin and also reduced in vitro migration of the cells. Whereas lovastatin and simvastatin significantly decreased the expression of CD44, atorvastatin drastically increased CD24 and caused more wide-ranging impacts. In summary, the statins hold back the process of EMT by the antagonizing of EMT-promoting pathways. High degree of overlapping findings is supportive of the central role of the mevalonate pathway in cancer stem-like cells, but further studies are required to find the optimized chemical structure for the maximum abrogation of orchestrated EMT pathways.

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lipophilic statins antagonistically alter the major epithelial‐to‐mesenchymal transition signaling pathways in breast cancer stem–like cells via inhibition of the mevalonate pathway

Koohestanimobarhan

Salami

Imeni

et al. 2018

J of Cellular Biochemistry

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“…Several studies used statin as part of ER-positive breast cancer treatment (27–28). Statin is a lipid-lowering drug commonly used to treat hyperlipidaemia and targeted the mevalonate pathway.…”

Section: Cholesterol Biosynthesis Pathway As a Novel Mechanism Of Resmentioning

confidence: 99%

Andrographolide is an Alternative Treatment to Overcome Resistance in ER-Positive Breast Cancer via Cholesterol Biosynthesis Pathway

Rajaratinam¹,

Nafi²

2019

MJMS

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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.

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“…These functions are related to cancer initiation, growth, and metastasis [20][21][22]. Therefore, FLUVA inhibits the proliferation and angiogenic and metastatic properties of breast cancer cells and BCSCs [23]. However, FLUVA has a low oral bioavailability (~24%), short halflife, and 98% plasma protein binding.…”

Section: Introductionmentioning

confidence: 99%

Repurposing of Fluvastatin as an Anticancer Agent against Breast Cancer Stem Cells via Encapsulation in a Hyaluronan-Conjugated Liposome

Shin

Kim

2020

Pharmaceutics

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Fluvastatin (FLUVA), which is a common anti-hypercholesterolemia drug, exhibits potential anticancer activity as it suppresses the proliferation, angiogenesis, and metastasis of breast cancer cells via inhibiting 3-hydroxy-methyl glutaryl-coenzyme A (HMG-CoA) reductase. In this study, hyaluronan-conjugated FLUVA-encapsulating liposomes (HA-L-FLUVA) were evaluated for their anticancer efficacy in vitro and in vivo. The particle size, zeta potential, and encapsulation efficiency of HA-L-FLUVA were 158.36 ± 1.78 nm, −24.85 ± 6.26 mV, and 35%, respectively. Growth inhibition of breast cancer stem cells (BCSCs) by HA-L-FLUVA was more effective than that by free FLUVA. The half maximal inhibitory concentration (IC50) values of FLUVA, L-FLVUA, and HA-L-FLUVA were 0.16, 0.17, and 0.09 μM, respectively. The in vivo anticancer effect of HA-L-FLUVA in combination with doxorubicin (DOX) was more effective than that of free FLUVA, free DOX, and HA-L-FLUVA. The longest survival of mice was achieved by treatment with FLUVA (15 mg/kg) and HA-L-FLUVA (15 mg/kg) + DOX (3 mg/kg), followed by HA-L-FLUVA (15 mg/kg), Dulbecco’s phosphate buffered saline, and DOX (3 mg/kg). No more than 10% body weight loss was observed in the mice injected with FLUVA, indicating that the drug was not toxic. Taken together, these results indicate that HA-L-FLUVA could serve as an effective anticancer drug by inhibiting the growth of both breast cancer cells and cancer stem cells.

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Statins could be new treatment option in women with oestrogen receptor positive breast cancer

Cited by 3 publications

References 1 publication

Lipophilic statins antagonistically alter the major epithelial‐to‐mesenchymal transition signaling pathways in breast cancer stem–like cells via inhibition of the mevalonate pathway

Lipophilic statins antagonistically alter the major epithelial‐to‐mesenchymal transition signaling pathways in breast cancer stem–like cells via inhibition of the mevalonate pathway

Andrographolide is an Alternative Treatment to Overcome Resistance in ER-Positive Breast Cancer via Cholesterol Biosynthesis Pathway

Repurposing of Fluvastatin as an Anticancer Agent against Breast Cancer Stem Cells via Encapsulation in a Hyaluronan-Conjugated Liposome

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