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Anti-breast cancer and toxicity studies of total secondary saponin from Anemone raddeana Rhizome on MCF-7 cells via ROS generation and PI3K/AKT/mTOR inactivation.
- Source :
-
Journal of ethnopharmacology [J Ethnopharmacol] 2020 Sep 15; Vol. 259, pp. 112984. Date of Electronic Publication: 2020 May 22. - Publication Year :
- 2020
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Abstract
- Ethnopharmacological Relevance: The rhizome of Anemone raddeana Regel (A. raddeana) is a famous traditional Chinese medicine (TCM) recorded in Chinese Pharmacopoeia for the treatment of carbuncle and swelling. Carbuncle swollen is an explanation of tumor in the theory of TCM and softening and resolving hard mass effects are one of the important pharmacological activities of A. raddeana.<br />Aim of the Study: We investigated the potential anti-breast cancer effect and toxicological properties of alkali-ethanol extract from A. raddeana, namely total secondary saponin (TSS).<br />Materials and Methods: Anti-proliferative effect of total saponin of A. raddeana (ATS) and TSS were tested using MTT assay. Hoechst staining, flow cytometry analysis, DCFH-DA fluorescence microscopy and western blot were carried out to evaluate the mechanisms of action of TSS. The potential anti-breast cancer activity and toxicological properties of TSS were tested in vivo.<br />Results: ATS and TSS could inhibit the proliferation of A549, HepG2, MCF-7, MDA-MB-231 and SKBr-3 cells, especially for MCF-7 cells. Flow cytometry analysis revealed that TSS (10, 12 and 15 μg/ml) could induce cell cycle arrest on G0/G1 phase and promote apoptosis of MCF-7 cells. TSS could increase Bax/Bcl-2 ratio, elevate cytochrome c levels in cytosol and activate caspase-3/9. In addition, TSS also induced ROS generation and inactivated PI3K/AKT/mTOR pathway which may involved in the mitochondrial dysfunction of MCF-7 cells. TSS showed slight toxic at the dosage of 100 and 200 mg/kg by oral administration without any toxic potential for 28 days. TSS (50, 100 and 200 mg/kg) showed significant inhibitory effect on growth of transplanted tumor in mice. At last, twenty-three C-3 monosaccharide oleanane-type triterpene saponins were tentatively identified, which may contributed to the anti-cancer activity of TSS.<br />Conclusion: This study demonstrated that TSS exhibited anti-proliferative and pro-apoptosis activities on MCF-7 cells via ROS-mediated activation of mitochondrial apoptosis pathway. TSS might be used as chemotherapeutic agent for the treatment of breast cancer with relatively low toxicity.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Subjects :
- A549 Cells
Animals
Antineoplastic Agents, Phytogenic isolation & purification
Antineoplastic Agents, Phytogenic toxicity
Apoptosis drug effects
Apoptosis Regulatory Proteins metabolism
Breast Neoplasms enzymology
Breast Neoplasms pathology
Cell Cycle Checkpoints drug effects
Cell Proliferation drug effects
Female
Hep G2 Cells
Humans
MCF-7 Cells
Mice, Inbred BALB C
Mice, Nude
Mitochondria drug effects
Mitochondria metabolism
Mitochondria pathology
Plant Extracts isolation & purification
Plant Extracts toxicity
Saponins isolation & purification
Saponins toxicity
Signal Transduction
Tumor Burden drug effects
Xenograft Model Antitumor Assays
Anemone chemistry
Anemone toxicity
Antineoplastic Agents, Phytogenic pharmacology
Breast Neoplasms drug therapy
Phosphatidylinositol 3-Kinase metabolism
Plant Extracts pharmacology
Proto-Oncogene Proteins c-akt metabolism
Reactive Oxygen Species metabolism
Rhizome chemistry
Rhizome toxicity
Saponins pharmacology
TOR Serine-Threonine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7573
- Volume :
- 259
- Database :
- MEDLINE
- Journal :
- Journal of ethnopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 32446927
- Full Text :
- https://doi.org/10.1016/j.jep.2020.112984