Researchers have discovered that panduratin A, a compound found in the medicinal plant Boesenbergia rotunda, exhibits potent anti-cancer properties against various types of leukemia and lymphoma. By conducting a comprehensive transcriptome analysis, the team identified the Forkhead box O (FOXO) transcription factor family as a key player in mediating the antileukemia and antilymphoma effects of panduratin A. The findings shed light on the molecular mechanisms underlying the therapeutic potential of this natural compound and highlight its possible applications in the treatment of blood-related cancers.
Uncovering the Medicinal Potential of Boesenbergia rotunda
Boesenbergia rotunda, commonly known as fingerroot, is a medicinal and culinary plant native to the Indochina Peninsula. Its rhizome (underground stem) has long been used in traditional medicine and has recently gained attention for its potential as a source of anti-cancer compounds. One of the primary bioactive compounds found in the fingerroot rhizome is panduratin A, which has demonstrated various biological activities, including antioxidant, anti-inflammatory, and anticancer properties.
Panduratin A: A Potent Inhibitor of Leukemia and Lymphoma
The researchers set out to investigate the anti-cancer potential of panduratin A against different types of leukemia and lymphoma cell lines. They found that panduratin A effectively inhibited cell proliferation, induced apoptosis (programmed cell death), and promoted cell cycle arrest at the G0/G1 phase in a dose-dependent manner. Interestingly, the researchers observed that the inhibitory effects of panduratin A were more pronounced in lymphoid lineage cell lines (such as Jurkat, Pfeiffer, and Toledo) compared to myeloid lineage cell lines (such as HL60 and K562).
Fig. 1
Unveiling the Molecular Mechanisms: Transcriptome Analysis
To gain a deeper understanding of the underlying mechanisms, the researchers performed a transcriptome analysis on B-cell lymphoma cell lines (Pfeiffer and Toledo) treated with panduratin A. This high-throughput technique allowed them to identify the differentially expressed genes (DEGs) in response to panduratin A treatment.
The analysis revealed that panduratin A primarily affected genes involved in cell cycle regulation, cellular senescence, apoptosis, and various signaling pathways. Notably, the Forkhead box O (FOXO) transcription factor family emerged as a potential target of panduratin A. The FOXO proteins play a crucial role in diverse cellular processes, including cell proliferation, apoptosis, and stress response.
Fig. 2
The FOXO Connection: A Key to Antileukemia/Lymphoma Activity
The researchers further investigated the role of FOXO proteins in the anti-cancer effects of panduratin A. They found that panduratin A treatment led to an increase in the expression of FOXO1, FOXO3, and FOXO4 mRNA in the leukemia and lymphoma cell lines. Interestingly, the Pfeiffer B-cell lymphoma cells showed the highest fold change in FOXO3 expression, suggesting a potentially crucial role for this particular FOXO isoform.
Western blot analysis revealed that panduratin A induced the phosphorylation of FOXO3, which is a key regulatory mechanism for its activity. Phosphorylation of FOXO3 by the Akt signaling pathway typically leads to its inactivation and exclusion from the nucleus, thereby preventing its tumor-suppressive functions.
Clinical Relevance and Future Directions
The researchers further examined the expression of FOXO3 in clinical specimens from patients with B-cell lymphoma. They found that FOXO3 was heterogeneously expressed in the neoplastic B cells, with the exception of Burkitt lymphoma, which showed no detectable FOXO3 expression. This observation suggests that the suppression of FOXO3 may be associated with more aggressive lymphoma subtypes, underscoring its potential as a prognostic marker.
Overall, this study highlights the therapeutic potential of panduratin A and its ability to target the FOXO transcription factor family, which play a crucial role in regulating cell proliferation, apoptosis, and stress response in leukemia and lymphoma. The findings pave the way for further investigations into the clinical applications of panduratin A and its derivatives as novel anti-cancer agents for the treatment of blood-related malignancies.
Author credit: This article is based on research by Suttinee Phuagkhaopong, Jiranan Janpattanapichai, Noppavut Sirirak, Phisit Khemawoot, Pornpun Vivithanaporn, Kran Suknuntha.
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