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Differential Anticancer Activity of Pterostilbene Against Three Subtypes of Human Breast Cancer Cells
Rei Wakimoto1, Misaki Ono1, Mikako Takeshima1
1Graduate School of Health and Nutritional Sciences, Nakamura Gakuen University, Fukuoka, Japan.
Abstract:
Although pterostilbene, a natural analog of resveratrol, has potent antitumor activity against several human cancer types, the possible inhibitory mechanisms against subtypes of human breast cancer with different hormone receptor and human epidermal growth factor receptor 2 (HER2) status remain unknown. We investigated the anticancer activity of pterostilbene using three subtypes of breast cancer cell lines. Pterostilbene treatment exhibited a dose-dependent antiproliferative activity, with the greatest growth inhibition observed in triple-negative MDA-MB-468 cells. Although pterostilbene arrested cell-cycle progression at the G0/G1 phase regardless of breast cancer subtype, its apoptosis-inducing activity was highly apparent in MDA-MB-468 cells. Pterostilbene induced strong and sustained activation of extracellular signal-regulated kinase (ERK) 1/2, with concomitant cyclin D1 suppression and p21 up-regulation, and inhibited the phosphorylation of AKT and mammalian target of rapamycin (mTOR), followed by subsequent up-regulation of BAX without affecting B-cell lymphoma-extra large (BCL-xL). Oral administration of pterostilbene significantly suppressed tumor growth in nude mice xenotransplanted with MDA-MB-468 cells. These data suggest a potential role of pterostilbene for prevention and treatment of human breast cancer, especially of triple-negative breast cancer.
Insights
Pterostilbene, a resveratrol analog, shows potent anticancer effects against human breast cancer, particularly triple-negative subtypes. It inhibits cell proliferation and induces apoptosis, suggesting its potential as a therapeutic agent.
Area of Science:
- Biochemistry
- Pharmacology
- Oncology
Background:
- Pterostilbene, a natural compound, exhibits antitumor properties.
- Mechanisms of pterostilbene against diverse human breast cancer subtypes are not fully understood.
- Breast cancer classification includes hormone receptor and HER2 status, influencing treatment.
Purpose of the Study:
- To investigate the anticancer activity and mechanisms of pterostilbene in different human breast cancer subtypes.
- To evaluate pterostilbene's efficacy in preclinical models of triple-negative breast cancer.
Main Methods:
- Utilized three human breast cancer cell lines representing different subtypes.
- Assessed pterostilbene's effects on cell proliferation, cell cycle progression, and apoptosis.
- Analyzed key signaling pathways including ERK, AKT, and mTOR.
- Evaluated in vivo tumor growth suppression in a mouse xenograft model.
Main Results:
- Pterostilbene demonstrated dose-dependent antiproliferative activity across subtypes, most notably in triple-negative MDA-MB-468 cells.
- Cell cycle arrest at G0/G1 phase was observed irrespective of subtype.
- Apoptosis induction was significantly pronounced in MDA-MB-468 cells.
- Pterostilbene modulated ERK, AKT, and mTOR signaling pathways, affecting downstream targets like cyclin D1, p21, and BAX.
- Oral pterostilbene administration suppressed tumor growth in vivo.
Conclusions:
- Pterostilbene exhibits significant anticancer effects against human breast cancer, with notable efficacy against triple-negative breast cancer.
- The compound's mechanisms involve cell cycle arrest, apoptosis induction, and modulation of critical signaling pathways.
- Pterostilbene holds promise for the prevention and treatment of human breast cancer, particularly triple-negative types.
