Depsipeptide and roxithromycin induce apoptosis of lymphoma cells by blocking extracellular signal-regulated kinase

Related Experiment Video

Updated: May 3, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

8.9K

Sohshi Morimura1, Makoto Sugaya, Hiromichi Kai

  • 1Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.

The Journal of Dermatology
|January 21, 2014
PubMed

Insights

The combination of depsipeptide (FK228) and roxithromycin (RXM) showed additive effects in reducing lymphoma cell survival. This drug combination may enhance tumor-killing effects, potentially benefiting cutaneous T-cell lymphoma patients.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Depsipeptide (FK228) is an approved histone deacetylase inhibitor for cutaneous T-cell lymphoma.
  • Roxithromycin (RXM), a macrolide antibiotic, can induce apoptosis in certain T-cell lines.
  • Chemokines may inhibit tumor cell apoptosis, influencing treatment efficacy.

Purpose of the Study:

  • To investigate the synergistic effect of combining FK228 and RXM on lymphoma cell survival.
  • To identify signaling pathways affected by FK228 and RXM, with or without chemokines.
  • To evaluate the potential of this drug combination for cancer therapy.

Main Methods:

  • In vitro assessment of FK228 and RXM effects on HUT-78, Ki-JK, and EL-4 lymphoma cells.
  • Dose-response analysis of drug-induced cell death and apoptosis.
  • Western blot analysis to examine Akt and extracellular signal-regulated kinase (ERK) phosphorylation.
  • Evaluation of drug combinations at specific concentrations.

Main Results:

  • FK228 and RXM additively decreased lymphoma cell numbers at specific doses.
  • Both drugs inhibited Akt and ERK phosphorylation in EL-4 cells.
  • ERK phosphorylation was significantly associated with cell number and apoptosis markers.
  • Combined FK228 and RXM reduced cell numbers more effectively than single agents.

Conclusions:

  • The combination of FK228 and RXM demonstrates additive cytotoxic effects against lymphoma cells.
  • The extracellular signal-regulated kinase (ERK) pathway appears critical for lymphoma cell survival.
  • This combination therapy shows promise for enhancing anti-lymphoma activity in vitro.
  • Further research may support the clinical application of FK228 and RXM in cutaneous T-cell lymphoma treatment.
Keywords:
CCL11CCL27depsipeptidelymphomaroxithromycin

More Related Videos

Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum06:12

Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum

Published on: May 3, 2024

3.4K
Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages06:47

Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages

Published on: May 24, 2019

6.9K

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.2K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.2K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.1K
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
12.0K