Background: Recognition of a new therapeutic agent may activate an alternative programmed cell
death for the treatment of breast cancer.
Objective: Here, it has been tried to evaluate the effects of Shikonin, a naphthoquinone derivative of Lithospermum
erythrorhizon, on the induction of necroptosis and apoptosis mediated by RIPK1-RIPK3 in the ER+ breast
cancer cell line, MCF-7.
Methods: In the current study, cell death modalities, cell cycle patterns, RIPK1 and RIPK3 expressions,
caspase-3 and caspase-8 activities, reactive oxygen species and mitochondrial membrane potential have been
evaluated in the Shikonin-treated MCF-7 cells.
Results: Necroptosis and apoptosis have been occurred by Shikonin, with a significant increase in RIPK1 and
RIPK3 expressions, although necroptosis was the major rout in MCF-7 cells. Shikonin significantly increased
the percentage of the cells in sub-G1 and also those in the later stages of cell cycle, which represents an increase
in necroptosis and apoptosis. Under caspase inhibition by Z-VAD-FMK, Shikonin has stimulated necroptosis,
which could be arrested by Nec-1. An increase in ROS levels and a decrease in the mitochondrial membrane
potential have also been observed.
Conclusion: On the basis of present findings, Shikonin has been suggested as a good candidate for the induction
of cell death in ER+ breast cancer, although further investigations, experimental and clinical, are required.