Bergenin Inhibits Cell Viability and Induces Apoptotic Cell Death in Leukemia MOLT-4 Cells

Background

Leukemia, a hematological malignancy resulting from impaired blood cell formation in the bone marrow, is a considerable global health challenge, inflicting major burdens on individuals and healthcare systems. Current therapeutic strategies for leukemia, while exhibiting efficacy in certain contexts, frequently encounter significant limitations such as severe adverse effects and the development of drug resistance.

Objectives

The current work was committed to investigating the anticancer mechanisms of bergenin against leukemia cells.

The cytotoxic level of bergenin at various concentrations of 5-60 µM against leukemia MOLT-4 cells was studied using the MTT assay. The cell cytotoxic nature of bergenin against MOLT-4 cells was evaluated using the LDH release assay. The dual staining assay was performed to scrutinize the apoptosis-inducing potential of the bergenin against MOLT-4 cells. The interaction of LDHA and LDHB with the bergenin was evaluated using AutoDock Vina and Discovery Studio Visualizer (DSV). In addition, the drug-likeness properties and the toxicity profile were identified by accessing the ProTox v3.0 server.

Results

The growth of leukemia MOLT-4 cells was markedly reduced after treatment with bergnin at elevated doses (5-60 μM). The bergenin administration significantly elevated the LDH activity in MOLT-4 cells, indicating cellular damage and cytotoxicity in response to bergenin treatment. Moreover, the bergenin treatment significantly increased apoptotic cell deaths in MOLT-4 cells, as evidenced by the dual staining results. The underlying mechanisms of this apoptosis were evaluated through computational analysis by targeting LDHA and LDHB, a significant enzyme in the glycolytic pathway, contributing to the rapid cell proliferation in leukemia. The molecular docking results revealed that the bergenin exhibited better interactions with the LDHA (Binding Affinity (BA) = -6.7 kcal/mol; RMSD = 2.392Å) and LDHB (BA= -7.1 kcal/mol; RMSD = 1.420Å). Meanwhile, the predicted drug-likeness properties and toxicity profile of the bergenin revealed that it could serve as a key compound to develop as a drug to treat leukemia in the future.

Conclusion

The findings of this work demonstrate that bergenin treatment notably suppresses proliferation and triggers apoptosis in leukemia MOLT-4 cells, which may occur due to the inhibition of LDHA and LDHB. These findings provide evidence that bergenin has the capacity to function as an anticancer candidate for the treatment of leukemia.