The anti-tumor effect of stigmasterol on sorafenib treated human breast cancer cell lines

elshamy, asmaa; Omran, Gamal A.; Abd‐Αlhaseeb, Mohammad M.; Houssen, Maha E.

doi:10.21203/rs.3.rs-1021248/v1

Cited by 4 publications

(2 citation statements)

References 19 publications

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“…(Manral et al, 2016; Priya, Jha, Satish Kumar, & Sabarathinam, 2022; Verma et al, 2018). The NF‐κB signaling activation is regulated by tumor suppressor genes loss, such as von Hippel–Lindau tumor suppressor (VHL), tumor protein p53 (TP53), phosphatase, and tensin homolog (PTEN), and by the expression of some oncogenes, such as the BCR activator of RhoGEF and GTPase (BCR)/ABL proto‐oncogene 1 (Manral et al, 2016; Omran, Abd‐Alhaseeb, & Houssen, 2021).…”

Section: Novel Molecular Signaling Cascades and Cancer: Critical Role...mentioning

confidence: 99%

The critical role of the phytosterols in modulating tumor microenvironment via multiple signaling: A comprehensive molecular approach

Khan

Shal

et al. 2023

Phytotherapy Research

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Cancer is the leading cause of mortality and morbidity worldwide, and its cases are rapidly increasing every year. Several factors contribute to the development of tumorigenesis. including radiation, dietary lifestyle, smoking, environmental, and genetic factors. The cell cycle is regulated by a variety of molecular signaling proteins. However, when the proteins involved in the cell cycle regulation are altered, cellular growth and proliferation are significantly affected. Natural products provide an important source of new drug development for a variety of ailments. including cancer. Phytosterols (PSs) are an important class of natural compounds reported for numerous pharmacological activities, including cancer. Various PSs, such as ergosterol, stigmasterol, sitosterol, withaferin A, etc., have been reported for their anti‐cancer activities against a variety of cancer by modulating the tumor microenvironment via molecular signaling pathways discussed within the article. These signaling pathways are associated with the production of pro‐inflammatory mediators, growth factors, chemokines, and pro‐apoptotic and anti‐apoptotic genes. These mediators and their upstream signaling are very active within the variety of tumors and by modulating these signalings, thus PS exhibits promising anti‐cancer activities. However, further high‐quality studies are needed to firmly establish the clinical efficacy as well the safety of the phytosterols.

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Section: Novel Molecular Signaling Cascades and Cancer: Critical Role...mentioning

confidence: 99%

The critical role of the phytosterols in modulating tumor microenvironment via multiple signaling: A comprehensive molecular approach

Khan

Shal

et al. 2023

Phytotherapy Research

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“…Studies have highlighted the synergistic anticancer effects that natural medicine monomers can exhibit when combined with chemotherapeutic drugs. For example, the influence of sigmasterol on sorafenib-treated human breast cancer cell lines [11] and the potential of rhamnazin to enhance the antitumour effects of sorafenib-treated human hepatocellular carcinoma (HCC) cell lines [12].…”

Section: Introductionmentioning

confidence: 99%

Potential antitumour effect of all-trans retinoic acid on regorafenib-treated human colon cancer cell lines

Hamad,

Mehana,

Abd-Al haseeb

et al. 2023

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Introduction Colorectal cancer (CRC) is a significant contributor to cancer-related mortality worldwide, ranking as the second leading cause of such deaths. Central to the progression of this malignancy is angiogenesis – a complex process orchestrated by vascular endothelial growth factor (VEGF). Regorafenib, a potent multikinase inhibitor, acts as a critical antagonist of multiple kinases involved in angiogenesis, proliferation, and metastasis. Conversely, all-trans retinoic acid (ATRA) has demonstrated compelling antitumour effects across various cancer types. This study aims to comprehensively evaluate the combined antitumour potential of ATRA and regorafenib in human colon cancer cell lines while elucidating the intricate molecular mechanisms that underlie their action. Material and methods Our investigative approach involved an enzyme-linked immunosorbent assay to meticulously analyse the levels of key players in the VEGF signalling pathway, including VEGF itself, activated protein kinase (AMPK), extracellular signal-regulated protein kinase 1 (ERK1), and nuclear factor kappa B (NF-κB). Additionally, we assessed caspase-3 activity as a fundamental marker of apoptosis. Results The combined use of ATRA and regorafenib exhibited a remarkable augmentation in both AMPK and caspase-3 activities. This was accompanied by a significant reduction in VEGF, ERK1, and NF-κB levels within human colon cancer cell lines subjected to regorafenib treatment. Conclusions Our findings underscore the remarkable antiproliferative, antiangiogenic, and proapoptotic effects resulting from the combined use of ATRA and regorafenib in the context of CRC. This modulation of tumourigenic processes is predominantly mediated through the VEGF signalling axis.

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Health Benefits and Pharmacological Properties of Stigmasterol

et al. 2022

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Stigmasterol is an unsaturated phytosterol belonging to the class of tetracyclic triterpenes. It is one of the most common plant sterols, found in a variety of natural sources, including vegetable fats or oils from many plants. Currently, stigmasterol has been examined via in vitro and in vivo assays and molecular docking for its various biological activities on different metabolic disorders. The findings indicate potent pharmacological effects such as anticancer, anti-osteoarthritis, anti-inflammatory, anti-diabetic, immunomodulatory, antiparasitic, antifungal, antibacterial, antioxidant, and neuroprotective properties. Indeed, stigmasterol from plants and algae is a promising molecule in the development of drugs for cancer therapy by triggering intracellular signaling pathways in numerous cancers. It acts on the Akt/mTOR and JAK/STAT pathways in ovarian and gastric cancers. In addition, stigmasterol markedly disrupted angiogenesis in human cholangiocarcinoma by tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor receptor-2 (VEGFR-2) signaling down-regulation. The association of stigmasterol and sorafenib promoted caspase-3 activity and down-regulated levels of the anti-apoptotic protein Bcl-2 in breast cancer. Antioxidant activities ensuring lipid peroxidation and DNA damage lowering conferred to stigmasterol chemoprotective activities in skin cancer. Reactive oxygen species (ROS) regulation also contributes to the neuroprotective effects of stigmasterol, as well as dopamine depletion and acetylcholinesterase inhibition. The anti-inflammatory properties of phytosterols involve the production of anti-inflammatory cytokines, the decrease in inflammatory mediator release, and the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Stigmasterol exerts anti-diabetic effects by reducing fasting glucose, serum insulin levels, and oral glucose tolerance. Other findings showed the antiparasitic activities of this molecule against certain strains of parasites such as Trypanosoma congolense (in vivo) and on promastigotes and amastigotes of the Leishmania major (in vitro). Some stigmasterol-rich plants were able to inhibit Candida albicans, virusei, and tropicalis at low doses. Accordingly, this review outlines key insights into the pharmacological abilities of stigmasterol and the specific mechanisms of action underlying some of these effects. Additionally, further investigation regarding pharmacodynamics, pharmacokinetics, and toxicology is recommended.

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The anti-tumor effect of stigmasterol on sorafenib treated human breast cancer cell lines

Cited by 4 publications

References 19 publications

The critical role of the phytosterols in modulating tumor microenvironment via multiple signaling: A comprehensive molecular approach

The critical role of the phytosterols in modulating tumor microenvironment via multiple signaling: A comprehensive molecular approach

Potential antitumour effect of all-trans retinoic acid on regorafenib-treated human colon cancer cell lines

Health Benefits and Pharmacological Properties of Stigmasterol

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