Statins in risk-reduction and treatment of cancer

Barbălată, Cristina; Tefas, Lucia Ruxandra; Achim, Marcela; Tomuță, Ioan; Porfire, Alina

doi:10.5306/wjco.v11.i8.573

Cited by 71 publications

(58 citation statements)

References 105 publications

(131 reference statements)

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“…This is due to the heterogeneity of prostate cancer and increased ectopic androgen synthesis. 15 Drugs that block androgen synthesis in tumor cells and enhance the blocking efficiency of AR receptors, such as abiraterone and enzalutamide, are widely used in clinical practice. The inadequacy of blocking androgens, such as AR mutations, AR splices, and other androgen synthesis pathways, remains a major clinical problem.…”

Section: Discussionmentioning

confidence: 99%

SQLE Mediates Metabolic Reprogramming to Promote LN Metastasis in Castration-Resistant Prostate Cancer

Huang

Dai

et al. 2021

OTT

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Background: Almost all metastatic hormone-sensitive prostate cancers (mHSPC) will develop into metastatic castration-resistant prostate cancer (mCRPC) after androgen deprivation therapy (ADT). The expression level of squalene monooxygenase (SQLE) is increased in CRPC cells and regulates cholesterol metabolism. This study verified the biological function and mechanisms of SQLE in CRPC. Methods: The expression of SQLE in human prostate cancer cells was overexpressed or silenced and its efficacy on cell survival was determined by the MTS test. Energy metabolism phenotype test was evaluated by XF real-time ATP rate assay, XF cell mitochondrial stress test, XF glycolysis stress test and XF mito fuel flex test. Cell migration and invasion were evaluated by colony formation assays and transwell assays; the expression of mRNA and protein was assessed by RT-qPCR and Western blot, respectively. Moreover, BALB/c nude mice model was performed to evaluate the lymph node metastasis. Results: In our study, we found that the expression level of SQLE was significantly increased in bicalutamide-resistant-C4-2B cells compared to LNCaP cells. SQLE knockdown partly restored the sensitivity of drug-resistant cells to bicalutamide and reduced lymph node metastasis by inhibiting fatty acid oxidation in mitochondria. We also found that terbinafine, the specific inhibitor of SQLE, can enhance the sensitivity of prostate cancer cells to bicalutamide. Conclusion:Our study revealed that SQLE is involved in the progression of castration resistance in CRPC through mediating metabolic reprogramming, presenting SQLE as a new target for the treatment of mCRPC.

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Section: Discussionmentioning

confidence: 99%

SQLE Mediates Metabolic Reprogramming to Promote LN Metastasis in Castration-Resistant Prostate Cancer

Huang

Dai

et al. 2021

OTT

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“…Statins have been shown to act in both antioxidant and anti-inflammatory capacities, as well as demonstrating antiproliferative activities against a number of cancers. [ 7 8 ]…”

Section: Introductionmentioning

confidence: 99%

Statin Type and Cancer Outcomes in Patients with Diabetes Type 2 and Solid Tumors

Ceacareanu

Jolly

Nimako

et al. 2021

Journal of Research in Pharmacy Practice

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Objective: Type 2 diabetes mellitus (T2DM) affects 10% of Americans and is associated with an increased incidence of cancer. Statins are first-line cholesterol-lowering medications in the treatment of hyperlipidemia. Several studies have demonstrated a relationship between statin use and reduced cancer incidence. We examined the cancer benefits of statin subtypes, with specific attention to disease-free survival (DFS) and overall survival (OS). Methods: This retrospective review included adults with T2DM diagnosed with solid tumors at Roswell Park Cancer Institute in Buffalo, NY, USA (2003–2010). Individuals with gestational diabetes, incomplete records, or diagnosed with rare solid tumors were excluded. Follow-up began at the date of diagnosis and ended with the first confirmed recurrence, death, or loss of contact. Demographics were assessed by Chi-square, Kaplan–Meier survival analyses, and Cox proportional hazards regression. Findings: Overall, 1102 patients met inclusion criteria, 52.1% of the study participants were female, and 578 participants (52.5%) died during the follow-up period which ranged from 0 to 156 months. Hydrophilic statin use was associated with improved DFS at 5-year follow-up (41.0% vs. 36.9%, P = 0.0077) compared to lipophilic statin use. Multivariate regression revealed that hydrophilic statins were associated with improved DFS (hazard ratio [HR]: 0.706, 95% confidence interval [CI]: 0.526–0.947) and OS (HR: 0.685, 95% CI: 0.503–0.934). Pravastatin was associated with improved OS (HR: 0.674, 95% CI: 0.471–0.964). Conclusion: In patients with T2DM and cancer, hydrophilic statins, and pravastatin in particular, are associated with improved DFS as well as OS. Further research examining the cancer-specific effects of hydrophilic and lipophilic statins is needed to better understand their beneficial effects.

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“…The physico-chemical properties of statins are important for their antiproliferative effects, the majority of studies pointing out significantly higher antiproliferative activity for the lipophilic ones [7,8]. Among those, SMV is the most studied, with numerous in vivo and in vitro studies proving a synergistic or additive effect of SMV in combination with a large number of chemotherapeutic drugs, including DOX [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

An Electrochemical Strategy for the Simultaneous Detection of Doxorubicin and Simvastatin for Their Potential Use in the Treatment of Cancer

et al. 2021

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The aim of this study was to develop a disposable, simple, fast, and sensitive sensor for the simultaneous electrochemical detection of doxorubicin (DOX) and simvastatin (SMV), which could be used in preclinical studies for the development of new pharmaceutical formulations for drug delivery. Firstly, the electrochemical behavior of each molecule was analyzed regarding the influence of electrode material, electrolyte solution, and scan rate. After this, the proper electrode material, electrolyte solution, and scan rate for both active substances were chosen, and a linear sweep voltammetry procedure was optimized for simultaneous detection. Two chronoamperometry procedures were tested, one for the detection of DOX in the presence of SMV, and the other one for the detection of DOX and SMV together. Finally, calibration curves for DOX and SMV in the presence of each other were obtained using both electrochemical methods and the results were compared. The use of amperometry allowed for a better limit of detection (DOX: 0.1 μg/mL; SMV: 0.7 μg/mL) than the one obtained in voltammetry (1.5 μg/mL for both drugs). The limits of quantification using amperometry were 0.5 μg/mL for DOX (dynamic range: 0.5–65 μg/mL) and 2 μg/mL for SMV (dynamic range: 2–65 μg/mL), while using voltammetry 1 μg/mL was obtained for DOX (dynamic range: 1–100 μg/mL) and 5 μg/mL for SMV (dynamic range: 5–100 μg/mL). This detection strategy represents a promising tool for the analysis of new pharmaceutical formulations for targeted drug delivery containing both drugs, whose association was proven to bring benefits in the treatment of cancer.

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Statins in risk-reduction and treatment of cancer

Cited by 71 publications

References 105 publications

SQLE Mediates Metabolic Reprogramming to Promote LN Metastasis in Castration-Resistant Prostate Cancer

SQLE Mediates Metabolic Reprogramming to Promote LN Metastasis in Castration-Resistant Prostate Cancer

Statin Type and Cancer Outcomes in Patients with Diabetes Type 2 and Solid Tumors

An Electrochemical Strategy for the Simultaneous Detection of Doxorubicin and Simvastatin for Their Potential Use in the Treatment of Cancer

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