New insights into the therapeutic potentials of statins in cancer

Liu, Chengyu; Chen, Hong; Hu, Bingbing; Shi, Jiajian; Chen, Yu‐Chen; Huang, Kun

doi:10.3389/fphar.2023.1188926

Cited by 11 publications

(4 citation statements)

References 144 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As famous and developed inhibitors of HMGCR, statins mediate the reduction of cholesterol and lead to interruption of their cell membrane structure and related biological functions, such as angiogenesis, apoptosis, and autophagy. Accumulating preclinical and clinical trials of statins in different cancers suggested an overall beneficial role of statins with a favorable safety profile in cancer treatment and prevention [149]. In some established meta-analysis studies, statin use was correlated with reduced risk of cancer development and cancer-specific mortality in cancer patients and was associated with favorable survival outcomes [150][151][152].…”

Section: Inhibitors and Clinical Therapeutic Implicationsmentioning

confidence: 99%

Squalene Epoxidase: Its Regulations and Links with Cancers

Zhang,

Cao,

Hong

et al. 2024

IJMS

View full text Add to dashboard Cite

Squalene epoxidase (SQLE) is a key enzyme in the mevalonate–cholesterol pathway that plays a critical role in cellular physiological processes. It converts squalene to 2,3-epoxysqualene and catalyzes the first oxygenation step in the pathway. Recently, intensive efforts have been made to extend the current knowledge of SQLE in cancers through functional and mechanistic studies. However, the underlying mechanisms and the role of SQLE in cancers have not been fully elucidated yet. In this review, we retrospected current knowledge of SQLE as a rate-limiting enzyme in the mevalonate–cholesterol pathway, while shedding light on its potential as a diagnostic and prognostic marker, and revealed its therapeutic values in cancers. We showed that SQLE is regulated at different levels and is involved in the crosstalk with iron-dependent cell death. Particularly, we systemically reviewed the research findings on the role of SQLE in different cancers. Finally, we discussed the therapeutic implications of SQLE inhibitors and summarized their potential clinical values. Overall, this review discussed the multifaceted mechanisms that involve SQLE to present a vivid panorama of SQLE in cancers.

show abstract

Section: Inhibitors and Clinical Therapeutic Implicationsmentioning

confidence: 99%

Squalene Epoxidase: Its Regulations and Links with Cancers

Zhang,

Cao,

Hong

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…Mevalonate pathway products, such as isopentenyl pyrophosphate (IPP), farnesyl pyrophosphate (FPP), and geranylgeranyl pyrophosphate (GPP), all enable protein prenylation of GTPases, mainly Ras and RhoA proteins [59]. Limitations on these processes impede the alteration of various cancer pathways, thereby increasing apoptosis while decreasing angiogenesis, inflammation, and metastasis [60]. All of which are crucial in the fight against cancer development and progression.…”

Section: Basic Understanding Of the Molecular Mechanism Of The Anti-c...mentioning

confidence: 99%

“…It demonstrates that statins are anti-angiogenic. This anti-angiogenic outcome of statins in cholesterol-independent patients is accomplished by inhibiting the RhoA/focal adhesion kinase/AKT pathways [60]. The initial development of tumor blood vessels, relying on endothelial progenitor cells through vasculogenesis, could be disrupted by statins, potentially impeding tumor growth.…”

Section: Basic Understanding Of the Molecular Mechanism Of The Anti-c...mentioning

confidence: 99%

Don’t Judge a Book by Its Cover: The Role of Statins in Liver Cancer

Piekuś-Słomka,

Mocan,

Shkreli

et al. 2023

Cancers

View full text Add to dashboard Cite

Statins, which are inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, are an effective pharmacological tool for lowering blood cholesterol levels. This property makes statins one of the most popular drugs used primarily to prevent cardiovascular diseases, where hyperlipidemia is a significant risk factor that increases mortality. Nevertheless, studies conducted mainly in the last decade have shown that statins might prevent and treat liver cancer, one of the leading causes of cancer-related mortality worldwide. This narrative review summarizes the scientific achievements to date regarding the role of statins in liver tumors. Molecular biology tools have revealed that cell growth and proliferation can be inhibited by statins, which further inhibit angiogenesis. Clinical studies, supported by meta-analysis, confirm that statins are highly effective in preventing and treating hepatocellular carcinoma and cholangiocarcinoma. However, this effect may depend on the statin’s type and dose, and more clinical trials are required to evaluate clinical effects. Moreover, their potential hepatotoxicity is a significant caveat for using statins in clinical practice. Nevertheless, this group of drugs, initially developed to prevent cardiovascular diseases, is now a key candidate in hepato-oncology patient management. The description of new drug-statin-like structures, e.g., with low toxicity to liver cells, may bring another clinically significant improvement to current cancer therapies.

show abstract

“…Clinical applications of ATOR in SCLC patients with dyslipidemia have been reported [14]. Recently, increasing preclinical and epidemiological evidence has been provoked that dyslipidemia is an important risk factor for carcinogenesis, statins are shown to exert possible prevention and intervention effects on cancers and promote sensitivity to anticancer drugs [15]. This study addressed the molecular and biochemical mechanisms of the antitumor e cacy of the co-treatment with ATOR and bevacizumab in the lung cancer mice model.…”

Section: Introductionmentioning

confidence: 96%

Co-treatment with atorvastatin and bevacizumab improved antitumor efficacy and biochemical status in lung cancer in vivo

El-Said,

Attia,

Salim

2024

Preprint

View full text Add to dashboard Cite

Lung cancer is one of the most common cancers worldwide. Atorvastatin (ATOR), an anti-cholesterol drug, was shown recently to employ a probable effect against lung cancer. Bevacizumab, a vascular endothelial growth factor (VEGF) monoclonal antibody antagonist, is a known lung cancer remedy. This study aimed to address the effects of co-treatment of ATOR and bevacizumab against mouse lung cancer. Male mice were divided into 5 groups. Group 1 (G1), was used as a normal control. Groups 2-5 were administered with urethane (Ure) (1mg/g) and butylated hydroxy-toluene (BHT) (150 or 200 mg/kg) for lung cancer initiation and promotion respectively. G2 was a carcinogen-only control. G3 was post-treated with 10 mg/kg ATOR. G4 was treated with 5 mg/kg bevacizumab. G5 was co-treated with ATOR and bevacizumab. Co-treatment with ATOR and bevacizumab significantly decreased the tumor incidences, multiplicities, and sizes as compared with each treatment alone. Also, the combination treatment has reduced the immunohistochemical proliferating cell nuclear antigen labeling indexes (PCNA LI%) in lung parenchyma and tumors. Further, the treatment with ATOR/bevacizumab has significantly caused a G0/1 cell cycle arrest, induced apoptosis in cells and tumors, and ameliorated the antioxidative stress parameters in lung tissues. Furthermore, co-treatment with ATOR/bevacizumab has shown upregulation of mitogen-activated protein kinase (MAPK) and downregulation of Heme oxygenase (HMOX1), nitric oxide synthase 2 (NOS2), and VEGF genes. Collectively, ATOR co-treatment has significantly improved bevacizumab's efficacy against lung cancer in mice, through induction of apoptosis, inhibition of cell proliferation, and causing G0/1 cell cycle arrest, without adverse side effects.

show abstract

New insights into the therapeutic potentials of statins in cancer

Cited by 11 publications

References 144 publications

Squalene Epoxidase: Its Regulations and Links with Cancers

Squalene Epoxidase: Its Regulations and Links with Cancers

Don’t Judge a Book by Its Cover: The Role of Statins in Liver Cancer

Co-treatment with atorvastatin and bevacizumab improved antitumor efficacy and biochemical status in lung cancer in vivo

Contact Info

Product

Resources

About