Garcinielliptone G from Garcinia subelliptica Induces Apoptosis in Acute Leukemia Cells.

Youngsook Yun,Yutaka Aoyagi,Yukio Hitotsuyanagi,Hideshi Inoue,Takeshi Kinoshita,Satoshi Yotsumoto,Koichi Takeya,Mariko Shioura,Yuji Takahashi

doi:10.3390/molecules26092422

Abstract

Cytotoxicity and apoptosis-inducing properties of compounds isolated from Garcinia subelliptica leaves were investigated. The hexane-soluble portion of MeOH extracts of G. subelliptica leaves that showed cytotoxic activity was separated to yield seven compounds 1–7. Chemical structure analysis using NMR spectroscopy and mass spectrometry confirmed that compound 1 was canophyllol, and compounds 2–7 were garcinielliptones N, O, J, G, F, and garcinielliptin oxide, respectively. Among them, garcinielliptone G (5) showed growth inhibition by causing apoptosis in THP-1 and Jurkat cells derived from human acute monocytic leukemia and T lymphocyte cells, respectively. Apoptosis induced by garcinielliptone G (5) was demonstrated by the detection of early apoptotic cells with fluorescein-labeled Annexin V and increases in cleaved caspase-3 and cleaved PARP protein levels. However, the addition of caspase inhibitor Z-VAD-FMK did not affect growth arrest or apoptosis induction. These results suggest that garcinielliptone G (5) can induce both caspase-3 activation and caspase-independent apoptosis. Therefore, garcinielliptone G (5) may be a potential candidate for acute leukemia treatment.

Highlights

Leukemia is a group of heterogeneous hematopoietic stem cell malignancies
Methanolic extracts of G. subelliptica leaves were found to be cytotoxic by the WST-1 assay (Figure S1a)
The isolated compounds were identified as canophyllol (1) [13], garcinielliptone N (2) [14], garcinielliptone O (3) [14], garcinielliptone J (4) [15], garcinielliptone G (5) [15], garcinielliptone F (6) [15], and garcinielliptin oxide (7) [16,17] by comparing their NMR and MS spectra with Molecules 2021,t2h6,oxsFeORinPEtEhReRElVitIEeWrature (Figure 1 and Figures S4–S10)

Summary

Introduction

Leukemia is a group of heterogeneous hematopoietic stem cell malignancies. It is characterized by abnormal accumulation of undifferentiated blasts capable of uncontrolled proliferation in the bone marrow, preventing normal blood cell production. Acute leukemia (AL) is a common malignancy among children and adults worldwide and is one of the most common deadly cancers [1]. AL includes acute myeloid leukemia and acute lymphoblastic leukemia. The application of risk-adapted therapy and improved supportive care have increased 5-year survival rates, relapse rates have not significantly changed. Conventional leukemia therapies have side effects, such as hepatotoxicity and myelosuppression [2]

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Conclusion