Rhodiola Rosea Extract Reduces Autophagy In Acute Myeloid Leukemia Transformed From Myelodysplastic Syndromes Tumor Xenograft Model

Myelodysplastic syndrome (MDS) encompasses a heterogeneous group of clonal hematopoietic stem cell disorders, characterized by ineffective hematopoiesis and a tendency to progress towards acute myeloid leukemia (AML). The autophagy process has been implicated in the pathophysiology of both disorders. MDS treatment usually focuses on reducing or preventing complications, and single-target drugs are ineffective. The identification of novel compounds with anti-leukemia activity, as well as understanding the molecular and cellular basis of the disease may provide new therapeutic opportunities for MDS. In this concern, natural compounds such as Rhodiola rosea are considered interesting for the development of drugs against various molecular targets. Phytochemicals analyses of R. rosea extracts (RRE) revealed the presence of several components including polyphenols. The aim of this study was to study RRE effects using human tumor xenograft model. A total of 2x10⁶ P39 cells (AML transformed from MDS), were subcutaneously injected in dorsal region of NOD.CB17-Prkdc^scid/J mice. Tumor volume was measured once every 7 days and RRE treatment initiated when tumors reached 100-200 mm³ (n=6). The dose of 250mg/Kg body was given once every day by oral route (gavage). Control group received vehicle only (n=6). After 14 days, mice were sacrificed; tumors were removed and autophagy-related protein expression was evaluated by Western blot. After 14 days treatment, there was reduction of approximately 30% in tumor volume compared to controls. We found increased expression of beclin-1 and STSQM1/p62, and also Bcl-2 expression. In conclusion, Rhodiola rosea extract treatment in AML transformed from MDS tumor xenograft model reduces tumor growth, with pronounced inhibition of autophagy process.