Apoptotic effect of a phytosterol-ingredient and its main phytosterol (β-sitosterol) in human cancer cell lines

Álvarez-Sala, Andrea; Attanzio, Alessandro; Tesoriere, Luisa; García‐Llatas, Guadalupe; Barberá, Reyes; Cilla, Antonio

doi:10.1080/09637486.2018.1511689

Cited by 48 publications

(28 citation statements)

References 36 publications

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“…However, epidemiological studies have suggested that increased consumption of phytosterols can reduce the risk of different cancers [19, 33, 38, 61]. Data from cancer cell lines have shown that β-sitosterol can reduce cell proliferation and induce apoptosis in addition to inhibiting adhesion, invasion, and migration [2, 4–6, 8, 50, 64, 65, 70]. β-sitosterol has also been shown to inhibit the growth of tumor xenografts, reduce progression of carcinogen-induced tumors, and prevent metastatic lung and lymph node colonization [5, 8, 28, 29, 54].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of mitochondrial respiration prevents BRAF-mutant melanoma brain metastasis

Sundstrøm

Prestegarden

Azuaje

et al. 2019

acta neuropathol commun

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Melanoma patients carry a high risk of developing brain metastases, and improvements in survival are still measured in weeks or months. Durable disease control within the brain is impeded by poor drug penetration across the blood-brain barrier, as well as intrinsic and acquired drug resistance. Augmented mitochondrial respiration is a key resistance mechanism in BRAF -mutant melanomas but, as we show in this study, this dependence on mitochondrial respiration may also be exploited therapeutically. We first used high-throughput pharmacogenomic profiling to identify potentially repurposable compounds against BRAF -mutant melanoma brain metastases. One of the compounds identified was β-sitosterol, a well-tolerated and brain-penetrable phytosterol. Here we show that β-sitosterol attenuates melanoma cell growth in vitro and also inhibits brain metastasis formation in vivo. Functional analyses indicated that the therapeutic potential of β-sitosterol was linked to mitochondrial interference. Mechanistically, β-sitosterol effectively reduced mitochondrial respiratory capacity, mediated by an inhibition of mitochondrial complex I. The net result of this action was increased oxidative stress that led to apoptosis. This effect was only seen in tumor cells, and not in normal cells. Large-scale analyses of human melanoma brain metastases indicated a significant role of mitochondrial complex I compared to brain metastases from other cancers. Finally, we observed completely abrogated BRAF inhibitor resistance when vemurafenib was combined with either β-sitosterol or a functional knockdown of mitochondrial complex I. In conclusion, based on its favorable tolerability, excellent brain bioavailability, and capacity to inhibit mitochondrial respiration, β-sitosterol represents a promising adjuvant to BRAF inhibitor therapy in patients with, or at risk for, melanoma brain metastases. Electronic supplementary material The online version of this article (10.1186/s40478-019-0712-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Inhibition of mitochondrial respiration prevents BRAF-mutant melanoma brain metastasis

Sundstrøm

Prestegarden

Azuaje

et al. 2019

acta neuropathol commun

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“…144,[181][182][183][184][185][186] β-Sitosterol controls the expression and activity of HPV E6 and p53, which induces the apoptosis and arrests the growth of CC cells. 187,188 Limitations of the current study include the lack of experiments that evaluate the anti-CC effects and toxicity of combined treatment of FDY2004 with other anticancer agents involved in chemotherapy, targeted therapy, and cancer immunotherapy. Further investigations are needed to expand the therapeutic application of herbal drugs as anticancer therapies.…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Understanding of the Anticancer Mechanisms of FDY2004 Against Cervical Cancer Based on Network Pharmacology

Lee¹,

Kang²,

Park³

et al. 2021

Natural Product Communications

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Herbal drugs are continuously being developed and used as effective therapeutics for various cancers, such as cervical cancer (CC); however, their mechanisms of action at a systemic level have not been explored fully. To study such mechanisms, we conducted a network pharmacological investigation of the anti-CC mechanisms of FDY2004, an herbal drug consisting of Moutan Radicis Cortex, Persicae Semen , and Rhei Radix et Rhizoma. We found that FDY2004 inhibited the viability of human CC cells. By performing pharmacokinetic evaluation and network analysis of the phytochemical components of FDY2004, we identified 29 bioactive components and their 116 CC-associated pharmacological targets. Gene ontology enrichment analysis showed that the modulation of cellular functions, such as apoptosis, growth, proliferation, and survival, might be mediated through the FDY2004 targets. The therapeutic targets were also key components of CC-associated oncogenic and tumor-suppressive pathways, including PI3K-Akt, human papillomavirus infection, IL-17, MAPK, TNF, focal adhesion, and viral carcinogenesis pathways. In conclusion, our data present a comprehensive insight for the mechanisms of the anti-CC properties of FDY2004.

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“…In this regard, Gajendran, Durai, Varier, and Chinnasamy [22] reported that Rinoxia B (4 and 10 µM), a phytosterol isolated from leaf extract of Datura inoxia, induces apoptosis via upregulation Bax/Bcl-2 ratio and inhibits cell proliferation through downregulation of cell cycle regulatory proteins (Cyclidin D1 and B1) and G 2 /M arrest in HCT 15 human colon adenocarcinoma cell line. Meanwhile Alvarez-Sala et al [243] indicated that phytosterols (β-sitosterol, sitostanol, campesterol, campestanol, and stigmasterol) from tall oil (13 µM) exert an antiproliferative effect in the breast (MCF-7), colon (HCT116), and cervical (HeLa) cancer cell lines, through the increase of sub-G1 cell population (apoptotic cells).…”

Section: Anti-cancermentioning

confidence: 99%

Antioxidant Molecules from Plant Waste: Extraction Techniques and Biological Properties

et al. 2020

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The fruit, vegetable, legume, and cereal industries generate many wastes, representing an environmental pollution problem. However, these wastes are a rich source of antioxidant molecules such as terpenes, phenolic compounds, phytosterols, and bioactive peptides with potential applications mainly in the food and pharmaceutical industries, and they exhibit multiple biological properties including antidiabetic, anti-obesity, antihypertensive, anticancer, and antibacterial properties. The aforementioned has increased studies on the recovery of antioxidant compounds using green technologies to value plant waste, since they represent more efficient and sustainable processes. In this review, the main antioxidant molecules from plants are briefly described and the advantages and disadvantages of the use of conventional and green extraction technologies used for the recovery and optimization of the yield of antioxidant naturals are detailed; finally, recent studies on biological properties of antioxidant molecules extracted from plant waste are presented here.

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Apoptotic effect of a phytosterol-ingredient and its main phytosterol (β-sitosterol) in human cancer cell lines

Cited by 48 publications

References 36 publications

Inhibition of mitochondrial respiration prevents BRAF-mutant melanoma brain metastasis

Inhibition of mitochondrial respiration prevents BRAF-mutant melanoma brain metastasis

A Comprehensive Understanding of the Anticancer Mechanisms of FDY2004 Against Cervical Cancer Based on Network Pharmacology

Antioxidant Molecules from Plant Waste: Extraction Techniques and Biological Properties

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