Targeting Cell Necroptosis and Apoptosis Induced by Shikonin via Receptor Interacting Protein Kinases in Estrogen Receptor Positive Breast Cancer Cell Line, MCF-7

Author(s): Zahra Shahsavari, Fatemeh Karami-Tehrani*, Siamak Salami.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 18 , Issue 2 , 2018

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Abstract:

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.

Keywords: Shikonin, Necroptosis, Apoptosis, ROS, Estrogen receptor positive, MCF-7.

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Article Details

VOLUME: 18
ISSUE: 2
Year: 2018
Page: [245 - 254]
Pages: 10
DOI: 10.2174/1871520617666170919164055
Price: $58

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