Clinical trials using human mesenchymal stem/stromal cells (hMSCs) for cell replacement therapy showed varied outcomes, where cells' efficacy has been perceived as the limiting factor. In particular, the quality and number of the expanded cells in vitro. In this study, we aimed to determine molecular signatures of hMSCs derived from the pulp of extracted deciduous teeth (SHED) and Wharton's jelly (WJSCs) that associated with cellular ageing during in vitro passaging. We observed distinct phenotypic changes resembling proliferation reduction, cell enlargement, an increase cell population in G2/M phase, and differentially expressed of tumor suppressor p53 in passage (P) 6 as compared to P3, which indicating in vitro cell senescence. The subsequent molecular analysis showed a set of diverse differentially expressed miRNAs and mRNAs involved in maintaining cell proliferation and stemness properties. Considering the signaling pathway related to G2/M DNA damage regulation is widely recognized as part of anti-proliferation mechanism controlled by p53, we explored possible miRNA-mRNA interaction in this regulatory pathway based on genomic coordinates retrieved from miRanda. Our work reveals the potential reason for SHED underwent proliferation arrest due to the direct impinge on the expression of CKS1 by miRNAs specifically miR-22 and miR-485-5p which lead to down regulation of CDK1 and Cyclin B. It is intended that our study will contribute to the understanding of these miRNA/mRNA driving the biological process and regulating different stages of cell cycle is beneficial in developing effective rejuvenation strategies in order to obtain quality stem cells for transplantation.
Cancer, a complex yet common disease, is caused by uncontrolled cell division and abnormal cell growth due to a variety of gene mutations. Seeking effective treatments for cancer is a major research focus, as the incidence of cancer is on the rise and drug resistance to existing anti-cancer drugs is major concern. Natural products have the potential to yield unique molecules and combinations of substances that may be effective against cancer with relatively low toxicity/better side effect profile compared to standard anticancer therapy. Drug discovery work with natural products has demonstrated that natural compounds display a wide range of biological activities correlating to anticancer effects. In this review, we discuss formononetin (C16H12O4), which originates mainly from red clovers and the Chinese herb Astragalus membranaceus. The compound comes from a class of 7-hydroisoflavones with a substitution of methoxy group at position 4. Formononetin elicits antitumorigenic properties in vitro and in vivo by modulating numerous signaling pathways to induce cell apoptosis (by intrinsic pathway involving Bax, Bcl-2, and caspase-3 proteins) and cell cycle arrest (by regulating mediators like cyclin A, cyclin B1, and cyclin D1), suppress cell proliferation [by signal transducer and activator of transcription (STAT) activation, phosphatidylinositol 3-kinase/protein kinase-B (PI3K/AKT), and mitogen-activated protein kinase (MAPK) signaling pathway], and inhibit cell invasion [by regulating growth factors vascular endothelial growth factor (VEGF) and Fibroblast growth factor 2 (FGF2), and matrix metalloproteinase (MMP)-2 and MMP-9 proteins]. Co-treatment with other chemotherapy drugs such as bortezomib, LY2940002, U0126, sunitinib, epirubicin, doxorubicin, temozolomide, and metformin enhances the anticancer potential of both formononetin and the respective drugs through synergistic effect. Compiling the evidence thus far highlights the potential of formononetin to be a promising candidate for chemoprevention and chemotherapy.