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Synergistic Effect of Ribitol and Shikonin Promotes Apoptosis in Breast Cancer Cells

Year: 2025

Type: article

Abstract: The mortality rate of breast cancer remains high, despite remarkable advances in chemotherapy. Therefore, it is imperative to identify new treatment options. In the present study, we investigated whether the metabolite ribitol enhances the cytotoxic effect of shikonin against breast cancer in vitro. Here, we screened a panel of small molecules targeting energy metabolism against breast cancer. The results of the study revealed that ribitol enhances shikonin’s growth-inhibitory effects, with significant synergy. A significant (p < 0.01) increase in the percentage (56%) of apoptotic cells was detected in the combined treatment group, compared to shikonin single-treatment group (38%), respectively. The combined ribitol and shikonin treatment led to significant arrest of cell proliferation (40%) (p < 0.01) compared to untreated cells, as well as the induction of apoptosis. This was associated with upregulation of p53 (p < 0.05) and downregulation of c-Myc (p < 0.01), Bcl-xL (p < 0.001), and Mcl-1 (p < 0.05). Metabolomic analysis supports the premise that inhibition of the Warburg effect is involved in shikonin-induced cell death, which is likely further enhanced by dysregulation of glycolysis and the tricarboxylic acid (TCA) cycle, afflicted by ribitol treatment. In conclusion, the present study demonstrates that the metabolite ribitol selectively enhances the cytotoxic effect mediated by shikonin against breast cancer in vitro.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms26062661

Authors: Ravi Doddapaneni, Jason D. Tucker, Pei J. Lu, Qi L. Lu

Institution: Carolinas Medical Center

Language: English

Topic: Bioactive Compounds and Antitumor Agents

Subfield: Toxicology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499