The effects and possible mechanism of action of apolipoprotein M on the growth of breast cancer cells

The CDK4/6 inhibitor palbociclib, combined with endocrine therapy, has been shown to be effective in postmenopausal women with oestrogen receptor positive, HER2-negative advanced or metastatic breast cancer. However, palbociclib is not as effective in the highly aggressive triple-negative breast cancer that lacks sensitivity to chemotherapy or endocrine therapy. We hypothesized that conjugation of the near-infrared dye MHI-148 with palbociclib can produce a potential theranostic in triple-negative as well as oestrogen receptor positive breast cancer cells. In our study, the conjugate was found to have enhanced activity in all mammalian cell lines tested in vitro. However, the conjugate was cytotoxic and did not induce G1 cell cycle arrest in breast cancer cells suggesting the mechanism of action differed from the parent compound palbociclib. The study highlights the importance of investigating the mechanism of conjugates of near-infrared dyes to therapeutic compounds as conjugation can potentially result in a change of mechanism or target, with an enhanced cytotoxic effect in this case.

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Faculty Opinions recommendation of Molecular mechanism of action of bisphenol and bisphenol A mediated by oestrogen receptor alpha in growth and apoptosis of breast cancer cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717976678.793472976 ◽

2013 ◽

Author(s):

Blesson Chellakkan Selvanesan

Keyword(s):

Breast Cancer ◽

Bisphenol A ◽

Cancer Cells ◽

Molecular Mechanism ◽

Mechanism Of Action ◽

Oestrogen Receptor ◽

Breast Cancer Cells ◽

Receptor Alpha ◽

Oestrogen Receptor Alpha ◽

Molecular Mechanism Of Action

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Unacylated ghrelin and AZP531 suppress the 3D growth of breast cancers

10.1101/2020.01.22.915744 ◽

2020 ◽

Author(s):

CheukMan C. Au ◽

John B. Furness ◽

Kara Britt ◽

Sofya Oshchepkova ◽

Heta Ladumor ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Mechanism Of Action ◽

Breast Cancer Cells ◽

Therapeutic Potential ◽

3D Culture ◽

Mapk Signaling ◽

Unacylated Ghrelin ◽

Ghrelin Receptor

ABSTRACTBreast cancer is the most common type of cancer in women and notwithstanding important therapeutic advances, it remains the second leading cause of cancer-related death in the US. Despite extensive research relating to the hormone ghrelin, responsible for the stimulation of growth hormone release and appetite, little is known of the effects of its unacylated form, especially in cancer. One major area of research relates to its reported effects to increase insulin sensitivity in diabetics, this being the basis for the development of unacylated ghrelin analog, AZP531 or livoletide, now in clinical trials for the treatment of Prader-Willi Syndrome. The mechanism of action of unacylated ghrelin is largely uncharacterized, in any system, because it does not bind to or activate the cognate ghrelin receptor, GHSR1a. The present study aimed to characterize effects of unacylated ghrelin on breast cancer cells, define its mechanism of action, and explore the therapeutic potential of unacylated ghrelin or analog AZP531. We report potent effects of unacylated ghrelin, at picomolar doses, on the growth of breast cancer cells, dependent on 3D culture and activation of Gαi. Suppression of MAPK signaling by unacylated ghrelin leads to cell cycle arrest and apoptosis. AZP531 also suppresses the growth of breast cancer cells in vitro and in xenografts, and may be a novel approach for the safe and effective treatment of breast cancer.

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