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

Ashraf Ullah Khan, Adnan Khan, Bushra Shal, Salman Khan, Majid Khan, Rizwan Ahmad, Muhammad Riaz

Journal: Phytotherapy research : PTR 2023;37(4):1606-1623

PMID: 36757068

Abstract

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.

© 2023 John Wiley & Sons Ltd.

Address: Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.; Faculty of Pharmaceutical Sciences, Abasyn University, Peshawar, Pakistan.; Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.; Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.; Faculty of Health Sciences, IQRA University, Islamabad Campus, (Chak Shahzad), Islamabad, Pakistan.; Faculty of Pharmaceutical Sciences, Abasyn University, Peshawar, Pakistan.; Natural Products & Alternative Medicines College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia.; Department of Pharmacy, Shaheed Benazir Bhutto University Sheringal, Sheringal, Pakistan.

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