Anticancer Potential of Apigenin and Isovitexin with Focus on Oncogenic Metabolism in Cancer Stem Cells

Abstract

It has been demonstrated that cancer stem cells (CSCs) go through metabolic changes that differentiate them from non-CSCs. The altered metabolism of CSCs plays a vital role in tumor initiation, progression, immunosuppression, and resistance to conventional therapy. Therefore, defining the role of CSC metabolism in carcinogenesis has emerged as a main focus in cancer research. Two natural flavonoids, apigenin and isovitexin, have been shown to act synergistically with conventional chemotherapeutic drugs by sensitizing CSCs, ultimately leading to improved therapeutic efficacy. The aim of this study is to present a critical and broad evaluation of the anti-CSC capability of apigenin and isovitexin in different cancers as novel and untapped natural compounds for developing drugs. A thorough review of the included literature supports a strong association between anti-CSC activity and treatment with apigenin or isovitexin. Additionally, it has been shown that apigenin or isovitexin affected CSC metabolism and reduced CSCs through various mechanisms, including the suppression of the Wnt/β-catenin signaling pathway, the inhibition of nuclear factor-κB protein expression, and the downregulation of the cell cycle via upregulation of p21 and cyclin-dependent kinases. The findings of this study demonstrate that apigenin and isovitexin are potent candidates for treating cancer due to their antagonistic effects on CSC metabolism.

Rafting on the Evidence for Lipid Raft-like Domains as Hubs Triggering Environmental Toxicants’ Cellular Effects

“…The ERalfa at membrane caveolae associates with G proteins, NOS3, Src kinases, phosphoinositide 3-kinase (PI3K)/Akt, JAK/STAT, and MAPKs [ 84 ]. This cluster of proteins partially coincides with the rafts-associated protein network further described in Section 4 and can underlie changes in cytosolic calcium and cAMP levels, dysregulation of nitric oxide production, and MAPK, PI3K, JAK/STAT, or Src/STAT pathway activation, processes implicated in environmental toxicants’ exposure, inflammation, and carcinogenesis [ 4 , 5 , 11 , 12 , 123 , 124 ]. These ER signalosome complexes could allow estrogen disruptors targeting lipid rafts to modify hormone signaling without direct interference with receptor-hormone binding.…”

Cancer Stem Cells from Definition to Detection and Targeted Drugs

“…Conventional chemotherapy and stem cell transplantation have augmented the survival of patients with AML, multiple myeloma, and other haematological malignancies, but additional therapeutic strategies are needed [161][162][163]. Cancer stem cells are a logical target for novel drugs and the modulation of oncogenic cell signalling, and metabolic alterations in stem cells have attracted special attention [161,[164][165][166]. The Wnt, Hedgehog, NF-κB, and Notch signalling routes play critical roles in the differentiation, proliferation, and survival of cancer stem cells [167,168], so various compounds have been developed targeting these pathways specifically.…”

Human diet‐derived polyphenolic compounds and hepatic diseases: From therapeutic mechanisms to clinical utilization

“…Apigenin, a common flavonoid, is widely distributed in various vegetables and fruits, especially parsley and celery. Over the past decades, many efforts have been made to verify the many pharmacological effects of apigenin, including anti‐inflammatory, antioxidant, and anticancer (Ghanbari‐Movahed et al, 2023; Moslehi et al, 2023). In recent years, attention has been gradually focused on the hepatoprotective effects of apigenin.…”