β-Sitosterol as a Promising Anticancer Agent for Chemoprevention and Chemotherapy: Mechanisms of Action and Future Prospects

Wang, Haoyu; Wang, Zhi; Zhang, Zihui; Liu, Jingchun; Li, Hong

doi:10.1016/j.advnut.2023.05.013

Cited by 23 publications

(9 citation statements)

References 266 publications

(364 reference statements)

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“…In previous studies, it has been reported that certain bioactive molecules, including UA, BA, GA, ST, and BT have inhibitory effects on tumor cells. 26 , 27 , 28 , 29 , 30 Therefore, we also investigated the inhibitory effects of these bioactive molecules on GBM and attempted to explore their combined effects with PTX. According to the results, at a concentration of 2 μM, certain bioactive molecular NPs exhibit inhibitory effects on U87MG, among which ST NPs demonstrated the strongest effect with an inhibition rate of 12.3% (Figure S1 ).…”

Section: Resultsmentioning

confidence: 99%

Self‐Assembled nanoparticles of natural bioactive molecules enhance the delivery and efficacy of paclitaxel in glioblastoma

Li,

Zhao,

Zhu

et al. 2023

CNS Neurosci Ther

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BackgroundGlioblastoma (GBM) is the most common primary malignant tumor in the central nervous system. Paclitaxel (PTX) is a well‐established and highly effective anti‐cancer drug for peripheral solid tumors. However, the application of PTX in GBM is hindered by several limitations, including poor water solubility, restricted entry across the blood–brain barrier (BBB), and enhanced excretion by efflux transporters. P‐glycoprotein (P‐gp) is a crucial efflux transporter that is abundantly present in cerebral vascular endothelial cells and GBM cells. It plays a significant role in the exocytosis of PTX within tumor tissues.MethodsRecently, we have developed a novel technique for creating self‐assembled nanoparticles utilizing a range of natural bioactive molecules. These nanoparticles can encapsulate insoluble drugs and effectively cross the BBB. In additional, we revealed that certain nanoparticles have the potential to act as P‐gp inhibitors, thereby reducing the excretion of PTX. In this study, we conducted a screening of bioactive molecular nanoparticles to identify those that effectively inhibit the function of P‐gp transporters.ResultsAmong the candidates, we identified ursolic acid nanoparticles (UA NPs) as the P‐gp inhibitors. Furthermore, we prepared co‐assembled UA NPs embedded with paclitaxel, referred to as UA‐PTX NPs. Our results demonstrate that UA‐PTX NPs can enhance the blood concentration of PTX, facilitate its entry into the BBB, and inhibit the function of P‐gp, resulting in a decrease in the excretion of PTX. This discovery effectively addressed the above three issues associated with the use of PTX in glioma treatment.ConclusionsUA‐PTX NPs demonstrate strong anti‐tumor effects and show great potential for treating GBM.

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Section: Resultsmentioning

confidence: 99%

Self‐Assembled nanoparticles of natural bioactive molecules enhance the delivery and efficacy of paclitaxel in glioblastoma

Li,

Zhao,

Zhu

et al. 2023

CNS Neurosci Ther

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“…β-Sitosterol is known to possess anticancer activity against various cancers. 47 A higher dietary intake of β-sitosterol is associated with a lower risk of ESCC, and phytosterol-rich foods or supplements are essential for preventing squamous esophageal cancer. 48 The ability of β-sitosterol to act on the five core genes identified was evaluated in this study.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Risk Models Using Epithelial Cells Identify β-Sitosterol as a Potential Therapeutic Target Against Esophageal Squamous Cell Carcinoma

Zhang,

Shang,

Mao

et al. 2024

IJGM

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Background Esophageal squamous cell carcinoma (ESCC) is an aggressive and fatal malignancy that leads to epithelial cancer. The association between epithelial cell heterogeneity, prognosis, and immune response in this cancer remains uncertain. This study aimed to investigate epithelial cell heterogeneity in ESCC and develop a predictive risk model using the identified cell types. Methods Single-cell RNA sequencing (scRNA-seq) and differential ESCC gene data were accessed from the Gene Expression Omnibus. Functional enrichment analysis, inferCNV, cell development trajectories, and intercellular communication were analyzed following epithelial cell characterization. Differentially expressed ESCC (n = 773) and epithelial cell marker genes (n = 3407) were intersected to obtain core genes, and epithelial cell-related prognostic genes were identified. LASSO regression analysis was used to construct a prognostic model. The external dataset GSE53624 was used to further validate the stability of the model. Drug sensitivity predictions, and immune cell infiltration were analyzed. Molecular docking clarified the possible therapeutic role of β-sitosterol in ESCC. Finally, wound healing assay, cell colony, and transwell assay were constructed to detect the effects of the core gene PDLIM2 on ESCC cell proliferation, invasion, and migration. Results Eight cell clusters were identified, and epithelial cells were categorized into tumor and paratumor groups. The tumor group possessed more chromosomal variants than the paratumor group. Epithelial cells were associated with multiple cell types and significantly correlated with the Wnt, transforming growth factor, and epidermal growth factor signaling pathways. From 231 intersected genes, five core genes were screened for use in the risk model: CTSL, LAPTM4B, MYO10, NCF2, and PDLIM2. These genes may contribute to the cancerous transformation of normal esophageal epithelial cells and thereby act as biomarkers and potential therapeutic targets in patients with ESCC. β-Sitosterol furthermore displayed excellent docking potential with these genes. Meanwhile, further experiments demonstrated that the gene PDLIM2 plays a major role in the progression of oesophageal squamous carcinoma. Conclusion We successfully developed a risk model for the prognosis of ESCC based on epithelial cells that addresses the response of ESCC to immunotherapy and offers novel cancer treatment options.

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“…After dietary intake, β-sitosterol arrives in the stomach and small intestine where it is integrated into mixed micelles with bile salts and other lipids; due to its high hydrophobicity, its incorporation into micelles is competitive and less efficient compared to cholesterol (Li et al, 2022). β-Sitosterol is absorbed through the enterocytes lining the gut wall predominantly via passive diffusion, although some data suggest active transport via Niemann-Pick C1-like 1 (NPC1L1) protein as well (Jesch et al, 2009;Wang et al, 2023). Once absorbed, β-sitosterol bypasses the hepatic portal circulation and directly enters the systemic circulation (Feng et al, 2018); it has been found to induce cytochrome P450 enzymes, particularly CYP3A4, which could have implications for drugphytosterol interactions (Hwang et al, 2008).…”

Section: Therapeutic Perspectives and Limitationsmentioning

confidence: 99%

Anticancer activity and other biomedical properties of β‐sitosterol: Bridging phytochemistry and current pharmacological evidence for future translational approaches

Nandi,

Nag,

Khatua

et al. 2023

Phytotherapy Research

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Sterols, including β‐sitosterol, are essential components of cellular membranes in both plant and animal cells. Despite being a major phytosterol in various plant materials, comprehensive scientific knowledge regarding the properties of β‐sitosterol and its potential applications is essential for scholarly pursuits and utilization purposes. β‐sitosterol shares similar chemical characteristics with cholesterol and exhibits several pharmacological activities without major toxicity. This study aims to bridge the gap between phytochemistry and current pharmacological evidence of β‐sitosterol, focusing on its anticancer activity and other biomedical properties. The goal is to provide a comprehensive understanding of β‐sitosterol's potential for future translational approaches. A thorough examination of the literature was conducted to gather relevant information on the biological properties of β‐sitosterol, particularly its anticancer therapeutic potential. Various databases were searched, including PubMed/MedLine, Scopus, Google Scholar, and Web of Science using appropriate keywords. Studies investigating the effects of β‐sitosterol on different types of cancer were analyzed, focusing on mechanisms of action, pharmacological screening, and chemosensitizing properties. Modern pharmacological screening studies have revealed the potential anticancer therapeutic properties of β‐sitosterol against various types of cancer, including leukemia, lung, stomach, breast, colon, ovarian, and prostate cancer. β‐sitosterol has demonstrated chemosensitizing effects on cancer cells, interfering with multiple cell signaling pathways involved in proliferation, cell cycle arrest, apoptosis, survival, metastasis invasion, angiogenesis, and inflammation. Structural derivatives of β‐sitosterol have also shown anti‐cancer effects. However, research in the field of drug delivery and the detailed mode of action of β‐sitosterol‐mediated anticancer activities remains limited. β‐sitosterol, as a non‐toxic compound with significant pharmacological potential, exhibits promising anticancer effects against various cancer types. Despite being relatively less potent than conventional cancer chemotherapeutics, β‐sitosterol holds potential as a safe and effective nutraceutical against cancer. Further comprehensive studies are recommended to explore the biological properties of β‐sitosterol, including its mode of action, and develop novel formulations for its potential use in cancer treatment. This review provides a foundation for future investigations and highlights the need for further research on β‐sitosterol as a potent superfood in combating cancer.

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β-Sitosterol as a Promising Anticancer Agent for Chemoprevention and Chemotherapy: Mechanisms of Action and Future Prospects

Cited by 23 publications

References 266 publications

Self‐Assembled nanoparticles of natural bioactive molecules enhance the delivery and efficacy of paclitaxel in glioblastoma

Self‐Assembled nanoparticles of natural bioactive molecules enhance the delivery and efficacy of paclitaxel in glioblastoma

Prognostic Risk Models Using Epithelial Cells Identify β-Sitosterol as a Potential Therapeutic Target Against Esophageal Squamous Cell Carcinoma

Anticancer activity and other biomedical properties of β‐sitosterol: Bridging phytochemistry and current pharmacological evidence for future translational approaches

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