# Chelidonine Induces Concurrent Elevation of pSer-STAT3 and Bcl-2 Levels in a Mitotic Subpopulation of Human T-Leukemia/Lymphoma Cells

## TL;DR

Chelidonine increases pSer-STAT3 and Bcl-2 levels in a specific group of leukemia/lymphoma cells during mitosis.

## Contribution

First single-cell evidence of concurrent serine phosphorylation of STAT3 and Bcl-2 in response to chelidonine.

## Key findings

- Chelidonine transiently elevates pSer-STAT3 and Bcl-2 in a mitotic subpopulation of T-leukemia/lymphoma cells.
- The effect is partially independent of IL-2 and linked to the M-phase of the cell cycle.
- Phosphorylation of Bcl-2 at serine 70 and mitotic nuclear morphology are observed.

## Abstract

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that regulates a broad spectrum of genes with oncogenic potential, thereby serving as a critical driver of tumorigenesis. Canonical STAT3 function is mediated through tyrosine phosphorylation, which enables dimerization and transcriptional activation, whereas serine phosphorylation of STAT3 has a postulated role in fine-tuning canonical functions and contributes to non-canonical roles as well. One of the transcriptional targets of STAT3 is the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein, itself subject to phosphorylation-dependent regulation. In this study, we investigated the effect of chelidonine, an alkaloid component of Chelidonium majus L., on STAT3/Bcl-2 signaling in human T leukemia/lymphoma cells, reported to have numerous effects in common with microtubule-targeting agents (MTAs). Flow cytometry and confocal microscopy revealed that chelidonine transiently increased both serine-phosphorylated STAT3 (pSer-STAT3) and Bcl-2 levels in a distinct subpopulation of cells, with near-complete overlap between the affected cells. This effect appeared at least partially independent of interleukin-2 (IL-2) and was associated with the M-phase of the cell cycle, as indicated by enhanced phosphorylation of Bcl-2 at serine 70 and nuclear morphology characteristic of mitosis. Our study provides the first single-cell evidence that STAT3 and Bcl-2 undergo concurrent serine phosphorylation as a response to chelidonine treatment, with the effect tightly linked to the M-phase.