Effects of Sulforaphane-Induced Cell Death upon Repeated Passage of Either P-Glycoprotein-Negative or P-Glycoprotein-Positive L1210 Cell Variants

Int J Mol Sci. 2022 Sep 16;23(18):10818. doi: 10.3390/ijms231810818.

Abstract

The expression of the membrane ABCB1 transporter in neoplastic cells is one of the most common causes of reduced sensitivity to chemotherapy. In our previous study, we investigated the effect of a single culture of ABCB1-negative (S) and ABCB1-positive variants of L1210 cells (R and T) in the presence of sulforaphane (SFN). We demonstrated that SFN induces the onset of autophagy more markedly in S cells than in R or T cells. In the current study, we focused on the effect of the repeated culture of S, R and T cells in SFN-containing media. The repeated cultures increased the onset of autophagy compared to the simple culture, mainly in S cells and to a lesser extent in R and T cells, as indicated by changes in the cellular content of 16 and 18 kDa fragments of LC3B protein or changes in the specific staining of cells with monodansylcadaverine. We conclude that SFN affects ABCB1-negative S cells more than ABCB1-positive R and T cells during repeated culturing. Changes in cell sensitivity to SFN appear to be related to the expression of genes for cell-cycle checkpoints, such as cyclins and cyclin-dependent kinases.

Keywords: ABCB1 transporter; LC3B protein; apoptotic proteins; autophagy; cyclin dependent kinases; cyclins; monodansylcadaverine; multidrug resistance; sulforaphane.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1* / genetics
  • Apoptosis*
  • Cell Death
  • Cell Line, Tumor
  • Cyclin-Dependent Kinases
  • Cyclins
  • Isothiocyanates / pharmacology
  • Sulfoxides / pharmacology

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Cyclins
  • Isothiocyanates
  • Sulfoxides
  • Cyclin-Dependent Kinases
  • sulforaphane