Back to Search
Start Over
Acetylshikonin isolated from Lithospermum erythrorhizon roots inhibits dihydrofolate reductase and hampers autochthonous mammary carcinogenesis in Δ16HER2 transgenic mice
Acetylshikonin isolated from Lithospermum erythrorhizon roots inhibits dihydrofolate reductase and hampers autochthonous mammary carcinogenesis in Δ16HER2 transgenic mice
- Source :
- Pharmacological research. 161
- Publication Year :
- 2020
-
Abstract
- Breast cancer (BC) is the most common cancer in women and, among different BC subtypes, triple negative (TN) and human epidermal growth factor receptor 2 (HER2)-positive BCs have the worst prognosis. In this study, we investigated the anticancer activity of the root ethanolic and hexane extracts from Lithospermum erythrorhizon, a traditional Chinese herbal medicine known also as tzu ts’ao or tzu-ken, against in vitro and in vivo models of TNBC and HER2-positive BC. Treatment with L. erythrorhizon root extracts resulted in a dose-dependent inhibition of BC cell viability and in a significant reduction of the growth of TNBC cells transplanted in syngeneic mice. Acetylshikonin, a naphthoquinone, was identified as the main bioactive component in extracts and was responsible for the observed antitumor activity, being able to decrease BC cell viability and to interfere with autochthonous mammary carcinogenesis in Δ16HER2 transgenic mice. Acetylshikonin anticancer effect depends on its ability to act as a potent inhibitor of dihydrofolate reductase (DHFR), to down-regulate key mediators governing cancer growth and progression, such as HER2, Src and STAT3, and to induce apoptosis by caspase-3 activation. The accumulation of acetylshikonin in blood samples as well as in brain, kidney, liver and tumor tissues was also investigated by liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) highlighting that L. erythrorhizon treatment is effective in delivering the active compound into the target tissues. These results provide evidence that L. erythrorhizon extract and in particular its main component acetylshikonin are effective against aggressive BC subtypes and reveal new acetylshikonin mechanisms of action.
- Subjects :
- 0301 basic medicine
Receptor, ErbB-2
Anthraquinones
Antineoplastic Agents
Apoptosis
Breast Neoplasms
Mice, Transgenic
Plant Roots
03 medical and health sciences
0302 clinical medicine
In vivo
Cell Line, Tumor
Dihydrofolate reductase
medicine
Animals
Humans
Tissue Distribution
Viability assay
STAT3
Cell Proliferation
Pharmacology
biology
Chemistry
Lithospermum
Cancer
medicine.disease
Lithospermum erythrorhizon
biology.organism_classification
Xenograft Model Antitumor Assays
In vitro
Tumor Burden
Tetrahydrofolate Dehydrogenase
030104 developmental biology
030220 oncology & carcinogenesis
biology.protein
Cancer research
Folic Acid Antagonists
Female
Signal Transduction
Subjects
Details
- ISSN :
- 10961186
- Volume :
- 161
- Database :
- OpenAIRE
- Journal :
- Pharmacological research
- Accession number :
- edsair.doi.dedup.....18040ddafd6bf3fb65ea7cbb39511c8c