Berberine-photodynamic induced apoptosis by activating endoplasmic reticulum stress-autophagy pathway involving CHOP in human malignant melanoma cells

Biochem Biophys Res Commun. 2021 May 7:552:183-190. doi: 10.1016/j.bbrc.2021.02.147. Epub 2021 Mar 19.

Abstract

Malignant melanoma is a critical and aggressive skin tumor with a steeply rising incidence and a less favorable prognosis due to the lack of efficient treatment. Photodynamic therapy (PDT) is a new promising treatment for this tumor through photosensitizers-mediated oxidative cytotoxicity. In this study, we explored the role of berberine-mediated PDT (BBR-PDT) in the anti-proliferative effect on human malignant melanoma cells (MMCs). We found that there were significant differences between MMCs with BBR-PDT and MMCs with BBR or PDT only. Further research showed that BBR-PDT induced apoptosis via up-regulating the expression of cleaved caspase-3 protein. We also observed that LC3-related autophagy level was upregulated in MMCs with BBR-PDT. Besides, it was also found that BBR-PDT activated endoplasmic reticulum (ER) stress, involving a dramatic increase in reactive oxygen species (ROS). Interestingly, the knockdown of CHOP protein expression inhibited apoptosis, autophagy and ER stress levels caused by BBR-PDT, suggesting that CHOP protein may be related to apoptosis, autophagy and ER stress in MMCs with BBR-PDT. Collectively, our results indicated that BBR-PDT had an essential impact on MMCs' growth inhibition, and therefore may reveal the possibility of developing BBR-PDT into human malignant melanoma.

Keywords: Apoptosis; Autophagy; Berberine (BBR); C/EBP homologous Protein (CHOP/GADD153); Endoplasmic reticulum (ER) stress; Photodynamic therapy (PDT).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / radiation effects
  • Autophagy / drug effects*
  • Autophagy / radiation effects
  • Berberine / chemistry
  • Berberine / pharmacology*
  • Blotting, Western
  • Cell Line, Tumor
  • Endoplasmic Reticulum Stress / drug effects*
  • Endoplasmic Reticulum Stress / radiation effects
  • Humans
  • Light
  • Melanoma / metabolism
  • Melanoma / pathology
  • Melanoma / therapy*
  • Molecular Structure
  • Photochemotherapy / methods*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / radiation effects
  • Transcription Factor CHOP / metabolism*

Substances

  • DDIT3 protein, human
  • Reactive Oxygen Species
  • Berberine
  • Transcription Factor CHOP