Metadichol, A natural ligand for expression of Yamanaka reprogramming factors in somatic and primary cancer cell lines

Abstract

The conversion of somatic cells back into induced pluripotent stem cells (iPSCs) or embryonic-like stem cells involves the introduction of four genes commonly called Yamanaka factors, i.e., Sox2, Oct4, Klf4, and c-Myc, into the cells. Because these genes and the viral vectors used to introduce them into cells have the potential to cause cancer, iPSC lines are not clinically useful. Most instances of direct reprogramming have achieved have been by the forced expression of defined factors using viral vectors. Here, we show that Metadichol® has the potential to generate iPSCs non-virally and may be helpful in clinical applications. Metadichol is a nanoformulation of long-chain alcohols derived from food. Quantitative real-time PCR (qRT-PCR) and western blotting showed that OCT4, SOX2, and Nanog are expressed when fibroblasts were treated with Metadichol at one picogram to 100 nanograms. Reverse-transcription PCR (RT-PCR) also revealed that OCT4, KLF4, Nanog, and Sox2 levels increased compared to controls by 4.01, 3.51 and 1.26, and 2.5-fold, respectively, in A549 cancer cells. In Colo-205 cells, OCT4, KLF4, and Sox2 were increased by 1.79, 13.17, and 2.25folds, respectively. Metadichol treatment with triple-negative primary breast cancer (HCAF-TNPBC) primary cancer cells led to multifold increases of OKSM factors by 19.6, 8.07, 2.45, and 6.91, folds increase in Metadichol concentration ranges one picogram to 100 nano grams. Metadichol is a natural product that induces the expression of Yamanaka factors needed for reprogramming and Klotho, an anti-aging gene, and curbs the expression of the TP53 gene, which is critical for reprogramming somatic cells into IPSCs.Metadichol increases endogenous vitamin C levels, leading to the efficient reprogramming of somatic cells into iPSCs. Metadichol is nontoxic and commercially available as a nutritional supplement. Thus, it can be directly tested in vivo in human subjects to confirm that cells can indeed be programmed into a state of induced pluripotency and cause the mitigation of disease conditions.

METADICHOL: A natural nano lipid emulsion that expresses all 48 Nuclear receptors in the Stem, somatic, and Cancer cells.

“…In this review, we provide an overview of the NRF2 signaling pathway and discuss its role in carcinogenesis.We also introduce the inhibition of NRF2 by nuclear receptors. Namani et al (21) showed that the NRF2 signaling pathway can be regulated Nuclear receptors such as RARα, RXRα, PPARγ, ERα, ERRβ, and GR inhibit Nrf2. Since these are expressed by both Stem and Fibroblasts it is not surprising that SHP is down regulated in stem cells and not expressed in Fibroblasts.…”

Metadichol® a nano lipid emulsion that expresses all 48 nuclear receptors in stem and somatic cells

“…In this review, we presented the NRF2 signaling pathway, discussed its role in carcinogenesis, and introduced the inhibition of NRF2 by NRs. In this context, (Namani et al 2014) revealed that the NRF2 signaling pathway can be regulated and inhibited with NRs such as RARα, RXRα, PPARγ, ERα, ERRβ, and GR (Raghavan, 2022). Since these are expressed by both stem cells and broblasts, SHP is expected to be downregulated in stem cells and not expressed in broblasts.…”