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Eucalyptus camaldulensis leaf extract enhances thalidomide efficacy in acute myeloid leukemia cells through modulation of mitochondrial energetics
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DOI:10.1186/s12906-026-05503-2.png)
Abstract
En 中文
Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by high relapse rates and poor prognosis. Leukemic stem cells (LSCs), a major driver of therapy resistance, rely predominantly on mitochondrial oxidative phosphorylation (OXPHOS) for survival. Targeting mitochondrial metabolism represents a promising therapeutic strategy. This study investigated the effect of Eucalyptus camaldulensis Dehnh. leaf extract, alone and in combination with thalidomide, on mitochondrial energetics in AML cells. An in vitro study was conducted using the human AML Kasumi-1 cell line. Cells were divided into four groups: control, thalidomide-treated, E. camaldulensis extract-treated, and combination-treated groups. The ethanolic extract was characterized by GC–MS and HPLC. Cell viability was assessed using WST-1 assay and IC₅₀ values were calculated. Gene expression of CD34, MFN1, MFN2, OPA1, and IL-6 was quantified by qRT-PCR. ATP levels were measured by ELISA. Mitochondrial length was assessed by transmission electron microscopy. E. camaldulensis extract significantly reduced Kasumi-1 cell viability in a concentration-dependent manner, both alone and in combination with thalidomide. The combination demonstrated an additive cytotoxic effect (CI = 1). The IC₅₀ values were 197.80 µg/mL for thalidomide, 30.26 µg/mL for the extract, and 28.26 µg/mL for the combination. Thalidomide alone or combined significantly downregulated IL-6 expression, while thalidomide increased MFN1 expression. The extract significantly downregulated IL-6 and mitochondrial fusion genes and reduced CD34 expression. Extract treatment decreased ATP levels and shortened mitochondrial length compared with untreated cells (p < 0.05). Eucalyptus camaldulensis extract disrupts mitochondrial energetics and LSC-associated pathways in AML cells. Its combination with thalidomide shows additive activity and may represent a complementary strategy to overcome metabolic-driven therapy resistance in AML.
Keywords:
Eucalyptus camaldulensis
Acute myeloid leukemia
Oxidative phosphorylation
Thalidomide
Mitochondrial dynamics
Journal
B
IF:
3.4
Papers:
273
Citations:
0
