Apigenin as an effective anticancer natural product: Spotlight on TRAIL, WNT/β‐catenin, JAK‐STAT pathways, and microRNAs

Abstract

Wealth of information gleaned from decades of high‐impact research work; scientists have disentangled the complicated web of versatile regulators that underlie cancer development and progression. Use of structural biology approaches and functional genomics have helped us to gain new insights into complex nature of cancer, and it is now clear that genetic/epigenetic mutations, overexpression of oncogenes, inactivation of tumor suppressors, loss of apoptosis, and versatility of protein binding partners have contributory roles in carcinogenesis and metastatic spread. It is becoming progressively more understandable that reprogramming of gene expression during and nontranscriptional changes during cancer development and progression are initiated and controlled by deregulated signal transduction cascades, all of which collectively create an incalculable complexity. Data obtained through preclinical and clinical trials revealed that alterations in the targeted oncogenes and other downstream, and parallel pathways played a central role in the development of resistance against different therapeutics. Phytochemicals have regained limelight, and different natural products are currently being tested for efficacy in preclinical studies. Apigenin, a plant‐derived flavonoid has considerable pharmacological value and is reportedly involved in the regulation of different signaling cascades. In this review, we have attempted to summarize rapidly evolving understanding of molecular biologists and pharmacologists about the potential of apigenin in the regulation of deregulated signaling pathways in different cancers. We have emphasized on the regulation of WNT/β‐catenin and janus kinase/signal transducers and activators of transcription (JAK‐STAT) pathways. We also comprehensively discuss how apigenin restored apoptosis in tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐resistant cancers. The review also gives a snapshot of microRNAs (miRNAs) that regulate wide‐ranging biological processes, and it is now clear that each miRNA can control hundreds of gene targets. Apigenin was noted to upregulate miR‐520b and miR‐101 in different cancers to inhibit tumor growth. Moreover, apigenin‐induced apoptotic rate was significantly higher when used in combination with miR‐423‐5p inhibitors or miR‐138 mimics. Better comprehension of linear and integrated signaling pathways will be helpful in effective therapeutic targeting of deregulated signaling pathways to inhibit/prevent cancer.

Abatement of the Stimulatory Effect of Copper Nanoparticles Supported on Titania on Ovarian Cell Functions by Some Plants and Phytochemicals

“…These doses correspond to those of CuNPs that can be ingested and that have been applied in previous animal experiments, both in vivo and in vitro [ 20 , 58 , 59 , 60 , 61 ]. The dose of the plant additives was selected on the basis of the doses used in the corresponding previous in vitro experiments [ 41 , 43 , 45 , 49 , 50 ]. These substances were dissolved in the culture medium just before their addition to the cells.…”

“…Rutin was able to prevent also the symptoms of polycystic ovarian syndrome [ 47 ]. Another flavonoid-type phytoestrogen, apigenin, is able to suppress proliferation and viability, and to promote oxidative stress and apoptosis in non-ovarian [ 48 , 49 ] and ovarian [ 50 ] cancer cells. It can restore ovarian folliculogenesis, ovulation, and steroidogenesis during polycystic ovarian syndrome [ 51 ].…”

The Aberrant Expression Levels of miR-423-5p and miR-664b-5p in Peripheral Blood of Patients With Familial and Sporadic Ovarian Carcinoma

“…The evaluation of these studies showed that in cancers with overexpression of miR-423-5p the apoptosis mechanisms induced by Apigenin was severely destroyed. miR-423-5p was reported to be frequently overexpressed in glioma stem cells, and signi cantly increased apigenin related apoptosis developed in the use of miR-423-5p inhibitors [26]. The overexpression of miR-423-5p was reported to increase the colonisation, mobility, migration, and invasion capacity of LAD cells (Human mast cell greed LAD1, and LAD2) [27], however, in rat studies was reported to induce the tumorigenesis, and brain metastasis [28].…”

Coptisine fromCoptis chinensisexerts diverse beneficial properties: A concise review

“…105 For example, apigenin from Epimedium koreanum Nakai, emodin from Rheum palmatum L, quercetin from Hypericun ascyron L and curcumin from Curcuma louga L are all reported to modulate various chronic diseases within safe dose range. [106][107][108][109] Here in this article, we systematically review the existing literature concerning coptisine's diverse beneficial properties, and this continues to support the recommendation that coptisine can be applied to the treatment for cancer, inflammation, CVDs and metabolic disorders.…”