Anti-Cancer Role of Dendrosomal Nano Solanine in Chronic Myelogenous Leukemia Cell Line through Attenuation of PI3K/AKT/mTOR Signaling Pathway and Inhibition of hTERT Expression

Abstract

Background: Solanine was primarily known as a toxic compound. Nonetheless, recently the apoptotic role of solanine through suppression of PI3K/AKT/mTOR signaling pathway has been shown against many malignancies except chronic myelogenous leukemia (CML). Sustaining aforementioned prosurvival pathway, BCR-ABL fused oncoprotein in CML activates NF-kB and c-MYC for apparent immortalizing factor hTERT. Since solanine is a poor water-soluble molecule, herein a nanocarrier was employed to intensify its pernicious effectiveness on cancerous cells. Objective: The current research aimed at evaluating the effect of dendrosomal nano solanine (DNS) on leukemic and HUVEC cells. Methods Results: Investigating the anticancer property of free and dendrosomal nano solanine (DNS) and the feasible interplaying between DNS and imatinib on leukemic cells, we figured out the potential inhibitory role of DNS and DNS+IM on cancerous cells in comparison with chemotherapy drugs. Moreover, results revealed that the encapsulated form of solanine was much more preventive on expression of PI3KCA, mTOR, NF-kB, c-MYC and hTERT accompanied by dephosphorelating AKT ptotein. Conclusion: The results advocate the hypothesis that DNS, rather than solanine, probably due to impressive penetration, can restrain the principal pro-survival signaling pathway in erythroleukemia K562 and HL60 cell lines and subsequently declined mRNA level of hTERT which causes drug resistance during a long-term treatment. Additionally, combinational treatment of DNS and IM could also bestow an additive anti-leukemic effect. As further clinical studies are necessary to validate DNS efficacy on CML patients, DNS could have the potency to be considered as a new therapeutic agent even in combination with IM.

Supremacy of nanoparticles in the therapy of chronic myelogenous leukemia

“…To target the overexpression of somatostatin receptor type 2 in CML, amino-PEGylated quantum dots nanoparticle was succinylated and coated with the ligand octreotide [ 72 ]. K562 cells treated with dendrosomal nano-formulated solanine (DNS), DNS+ imatinib showed increased apoptosis and inhibited the expression of c-MYC, hTERT, NF-kB, mTOR, PI3KCA and also dephosphorylated the AKT protein [ 73 ]. Multidrug resistance (MDR) in CML was overcome by co-encapsulation of mitoxantrone and a P-glycoprotein(P-gp) inhibitor in β-elemene, the solid lipid nanoparticles.…”

Signaling pathways governing the behaviors of leukemia stem cells

“…14 Therefore, understanding the molecular etiology and signaling pathways involved in the occurrence and progression of leukemia provides a potential avenue for future therapeutic research and treatment. 15 , 16 Cancer stem cells (CSCs) are a small subgroup of tumor cells that play an essential role in tumorigenesis and tumor resistance. 17 CSCs have self-renewal and differentiation properties.…”