Simultaneous Treatment with Statins and Aspirin Reduces the Risk of Prostate Cancer Detection and Tumorigenic Properties in Prostate Cancer Cell Lines

Oliván, Mireia; Rigau, Marina; Colás, Eva; García, Marta; Montes, Melania; Sequeiros, Tamara; Regis, Lucas; Celma, Ana; Planas, Jacques; Placer, J.; Reventós, Jaume; Torres, Inés de; Doll, Andreas; Moróte, Juan

doi:10.1155/2015/762178

Cited by 21 publications

(27 citation statements)

References 49 publications

(51 reference statements)

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“…The investigators also evaluated the in vitro effects of aspirin, simvastatin and the combination in LNCaP and PC3 cells. The combination of aspirin and simvastatin significantly reduced proliferation in both LNCaP and PC-3 cells compared to the untreated control with no comparison to either drug alone (38). The in vivo effect of the drug combination was not investigated in this study.…”

Section: Discussionmentioning

confidence: 90%

“…A recent retrospective case-control study in Mediterranean men undergoing a prostate biopsy reported the use of the combination of aspirin and statins resulted in significantly less men diagnosed with prostate cancer compared to the untreated group (p<0001) (38). The investigators also evaluated the in vitro effects of aspirin, simvastatin and the combination in LNCaP and PC3 cells.…”

Section: Discussionmentioning

confidence: 99%

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Combined effects of atorvastatin and aspirin on growth and apoptosis in human prostate cancer cells

Huang

Farischon

et al. 2017

Oncology Reports

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Epidemiologic studies indicate the use of either statins or aspirin have beneficial effects in prostate cancer patients. The present study was undertaken to evaluate the effects and mechanisms of atorvastatin and aspirin alone or in combination in human prostate cancer cells cultured in vitro and grown as xenograft tumors in severe combined immune-deficient (SCID) mice. The growth and apoptosis in prostate cancer cells were determined by the trypan blue exclusion and propidium iodide staining assays. Activation of the nuclear factor κB (NF-κB) was measured by luciferase reporter assay, and the levels of phospho-signal transducer and activator of transcription (Stat)3 and phospho-extracellular signal-regulated kinase (Erk)1/2 were determined by western blot analysis. Mice were injected subcutaneously with PC-3 cells in Matrigel. After 4-6 weeks, mice with PC-3 tumors received i.p. injections of vehicle, atorvastatin (5 mg/kg), aspirin (80 mg/kg), or atorvastatin (5 mg/kg) + aspirin (80 mg/kg) three times a week for 30 days. Our results demonstrated the combination of atorvastatin and aspirin had more potent effects on growth inhibition and apoptosis stimulation in prostate cancer cells than either drug alone. Mechanistic studies indicated the induction of apoptosis in PC-3 cells was associated with strong inhibition of NF-κB and decreases in the levels of phospho-Stat3 and phospho-Erk1/2. Results of the present study demonstrated a strong combined effect of atorvastatin and aspirin on inhibiting the growth of prostate cancer cells in vitro and in vivo. The findings provide a strong rationale for clinical evaluation of the combination of atorvastatin and aspirin in patients with prostate cancer.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Combined effects of atorvastatin and aspirin on growth and apoptosis in human prostate cancer cells

Huang

Farischon

et al. 2017

Oncology Reports

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“…The dose of aspirin is varied depend on different diseases, such as 75-325 mg/day for cardiovascular disease, ≤325 mg/day for osteoarthritis and rheumatoid arthritis, and low dose of 75-300 mg/day for colorectal cancer and endometrial cancer (8,31-33). In addition, in vitro experiments, the effective doses of aspirin in most studies in colon, prostate or breast cancer cells vary from 1-10 mmol/l (26,34,35). our data suggested that the IC 50 value of aspirin for cell growth inhibition was 4.23 mmol/l.…”

Section: Discussionmentioning

confidence: 60%

Aspirin inhibits the proliferation of human uterine leiomyoma cells by downregulation of K-Ras-p110α interaction

et al. 2017

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Aspirin has been confirmed as an effective antitumor drug in various cancers. However, the relationship between aspirin and uterine leiomyoma is still underexplored. Here, we explored the effects of aspirin on human uterine leiomyoma cells and provide insights into the underlying mechanisms. Cell Counting Kit-8 (CCK-8) and flow cytometry analysis showed that aspirin treatment inhibited cell proliferation and promoted cell cycle arrest at G0/G1 phase in a dose- and time‑dependent manner of human uterine leiomyoma cells. Further studies revealed that aspirin blocked the interaction between K-Ras and p110α by co-immunoprecipitation and immunofluorescence. Western blotting demonstrated K‑Ras‑p110α interaction was required for the effects of aspirin‑induced inhibition on cell growth and cell cycle transition via cell cycle regulators, including cyclin D1 and cyclin-dependent kinase 2 (CDK2). PI3K/Akt/caspase signaling pathway was involved in human uterine leiomyoma cell growth under aspirin treatment. Taken together, these results suggest that aspirin inhibited human uterine leiomyoma cell growth by regulating K‑Ras‑p110α interaction. Aspirin which targeting on interaction between K-Ras and p110α may serve as a new therapeutic drug for uterine leiomyoma treatment.

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“…When combined with statins in treatment, aspirin was shown to decrease proliferation of LNCaP cells with a reduction in cyclin D1 levels—which modulates cell cycle progression (Olivan et al, 2015). Aspirin, on its own, was shown to cause ubiquitin-dependent degradation of cyclin D1 in colorectral cancer cells (Thoms et al, 2007).…”

Section: Aspirin and Cox-independent Regulation Of The Cell Cycle In mentioning

confidence: 99%

Prostate Cancer and Aspirin Use: Synopsis of the Proposed Molecular Mechanisms

2017

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Background: Prostate cancer (PCa) is a critical health burden, impacting the morbidity and mortality of millions of men around the world. Most of the patients with PCa have their disease at first sensitive to androgen deprivation treatments, but later they develop resistance to therapy and eventually die of metastatic castration-resistant prostate cancer (CRPC). Although the newly developed anti-androgen therapies are effectively alleviating symptoms and prolonging lives of patients, there are still no curable treatments for CRPC. Recently, statistical studies have shown that the chronic use of aspirin might be significantly associated with better outcomes in PCa patients. Through this review, we aim to identify the different proposed molecular mechanisms relating aspirin to the pathobiology of PCa neoplasms, with a major focus on basic research done in this context.Methods: Articles were retrieved via online database searching of PubMed and MEDLINE between 1946 and September 2016. Keywords and combinations related to PCa and aspirin were used to perform the search. Abstracts of the articles were studied by two independent reviewers and then data extraction was performed on the relevant articles that met our review objectives.Results: Aspirin, a non-steroidal anti-inflammatory drug (NSAID), affects the proliferation, apoptosis, resistance and metastasis of PCa cell lines, through both COX-dependent and COX-independent mechanisms. It also lowers levels of the PCa diagnostic marker prostate specific antigen (PSA), suggesting that clinicians need to at least be aware if their patients are using Aspirin chronically.Conclusion: This review strongly warrants further consideration of the signaling cascades activated by aspirin, which may lead to new knowledge that might be applied to improve diagnosis, prognosis and treatment of PCa.

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Simultaneous Treatment with Statins and Aspirin Reduces the Risk of Prostate Cancer Detection and Tumorigenic Properties in Prostate Cancer Cell Lines

Cited by 21 publications

References 49 publications

Combined effects of atorvastatin and aspirin on growth and apoptosis in human prostate cancer cells

Combined effects of atorvastatin and aspirin on growth and apoptosis in human prostate cancer cells

Aspirin inhibits the proliferation of human uterine leiomyoma cells by downregulation of K-Ras-p110α interaction

Prostate Cancer and Aspirin Use: Synopsis of the Proposed Molecular Mechanisms

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