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

Abstract

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: SOX2, OCT4, KLF4, and c-MYC. One drawback is that these genes and the viral vectors used to introduce them into cells have the potential to cause cancer, and these iPSC lines are not clinically useful. Most instances of direct reprogramming have been achieved by the forced expression of defined factors using viral vectors. In this paper, we show that Metadichol® has the potential to generate iPSCs non-virally and may be helpful in clinical applications. Metadichol is a Nano formulation 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 concentrations of one picogram to 100 nanograms. Reverse-transcription PCR (RT-PCR) resulted in OCT4, KLF4, NANOG, and SOX2 levels increased relative to controls by 4.01, 3.51 and 1.26, and 2.5 times, respectively. Such multifold increases were also seen in A549 cancer cell lines and in Colo-205 cells. Reprogramming human primary cancer cells remains a challenge. We present data that even primary cancer cells show increases in the four Yamanaka factors. Metadichol treatment of triple-negative primary breast cancer (HCAF-TNPBC) primary cancer cells led to increases in OKSM factors by 19.6, 8.07, 2.45, and 6.91 times in concentration ranges of 1 picogram to 100 nanograms. Metadichol induces the expression of Klotho, an antiaging gene, that curbs the expression of the TP53 gene, as this is a pre-requisite for reprogramming somatic cells into iPSCs. Metadichol also increases endogenous vitamin C levels, which is necessary for the efficient reprogramming of somatic cells into iPSCs. Metadichol an extract from food that is nontoxic, which opens the door to direct testing in humans with the potential for applications in stem cell therapy