# Periplocin Targets HDAC10 to Inhibit NF-κB Signaling and Induce Apoptosis in Myeloid Leukemia Cells

## TL;DR

Periplocin, a natural compound, fights leukemia by targeting HDAC10 and blocking NF-κB signaling, leading to cancer cell death.

## Contribution

Periplocin is identified as a novel natural compound that inhibits HDAC10 to induce apoptosis in myeloid leukemia cells.

## Key findings

- Periplocin binds to HDAC10 and inhibits its enzymatic activity.
- HDAC10 inhibition by periplocin disrupts NF-κB signaling and induces apoptosis in leukemia cells.
- Periplocin causes cell cycle arrest in myeloid leukemia cells.

## Abstract

Background: Periplocin, a bioactive compound extracted from Cortex periplocae, has long been employed in traditional medicine for its diverse therapeutic effects, particularly in alleviating inflammation and inhibiting cancer progression. However, despite its potential benefits, the underlying molecular mechanisms of periplocin, especially in the context of leukemia treatment, remain poorly elucidated, warranting further investigation to uncover its precise role and therapeutic targets.

Methods: A comprehensive approach combining network pharmacology and transcriptomic analysis was utilized to identify HDAC10 as a critical downstream target of periplocin. Molecular docking and dynamic simulation studies were performed to elucidate the interaction between periplocin and HDAC10 at the molecular level. Additionally, functional assays, including apoptosis induction, cell cycle regulation, and pathway inhibition experiments, were conducted to validate the mechanistic role of HDAC10 and its relevance to periplocin's anti-leukemic effects.

Results: Periplocin was identified as an effective inhibitor of HDAC10, binding specifically to its hydrophobic active pocket and suppressing its enzymatic activity. This inhibition disrupted downstream signaling, particularly the NF-κB pathway, leading to significant apoptosis and cell cycle arrest in leukemia cells. These results therapy, offering insights into its mechanism of action through HDAC10 targeting.

Conclusion: In conclusion, periplocin, as a novel natural compound, exhibits significant anti-leukemia activity, highlighting its potential as a promising therapeutic candidate for leukemia treatment. The findings contribute to the growing interest in natural compounds as innovative solutions for addressing unmet clinical needs in hematological malignancies.