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Tanshinone I attenuates the malignant biological properties of ovarian cancer by inducing apoptosis and autophagy via the inactivation of PI3K/AKT/mTOR pathway.
Cell Prolif. 2020 Feb; 53(2):e12739.CP

Abstract

OBJECTIVES

Tanshinone I (Tan-I) is one of the vital fatsoluble monomer components, which extracted from Chinese medicinal herb Salvia miltiorrhiza Bunge. It has been shown that Tan-I exhibited anti-tumour activities on different types of cancers. However, the underlying mechanisms by which Tan-Ⅰ regulates apoptosis and autophagy in ovarian cancer remain unclear. Thus, this study aimed to access the therapy effect of Tan-Ⅰ and the underlying mechanisms.

METHODS

Ovarian cancer cells A2780 and ID-8 were treated with different concentrations of Tan-Ⅰ (0, 1.2, 2.4, 4.8 and 9.6 μg/mL) for 24 hours. The cell proliferation was analysed by CCK8 assay, EdU staining and clone formation assay. Apoptosis was assessed by the TUNEL assay and flow cytometry. The protein levels of apoptosis protein (Caspase-3), autophagy protein (Beclin1, ATG7, p62 and LC3II/LC3I) and PI3K/AKT/mTOR pathway were determined by Western blot. Autophagic vacuoles in cells were observed with LC3 dyeing using confocal fluorescent microscopy. Anti-tumour activity of Tan-Ⅰ was accessed by subcutaneous xeno-transplanted tumour model of human ovarian cancer in nude mice. The Ki67, Caspase-3 level and apoptosis level were analysed by immunohistochemistry and TUNEL staining.

RESULTS

Tan-Ⅰ inhibited the proliferation of ovarian cancer cells A2780 and ID-8 in a dose-dependent manner, based on CCK8 assay, EdU staining and clone formation assay. In additional, Tan-Ⅰ induced cancer cell apoptosis and autophagy in a dose-dependent manner in ovarian cancer cells by TUNEL assay, flow cytometry and Western blot. Tan-Ⅰ significantly inhibited tumour growth by inducing cell apoptosis and autophagy. Mechanistically, Tan-Ⅰ activated apoptosis-associated protein Caspase-3 cleavage to promote cell apoptosis and inhibited PI3K/AKT/mTOR pathway to induce autophagy.

CONCLUSIONS

This is the first evidence that Tan-Ⅰ induced apoptosis and promoted autophagy via the inactivation of PI3K/AKT/mTOR pathway on ovarian cancer and further inhibited tumour growth, which might be considered as effective strategy.

Authors+Show Affiliations

College of Science, Sichuan Agricultural University, Ya'an, China.College of Science, Sichuan Agricultural University, Ya'an, China.College of Science, Sichuan Agricultural University, Ya'an, China.College of Life Science, China West Normal University, Nanchong, China.College of Science, Sichuan Agricultural University, Ya'an, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31820522

Citation

Zhou, Jin, et al. "Tanshinone I Attenuates the Malignant Biological Properties of Ovarian Cancer By Inducing Apoptosis and Autophagy Via the Inactivation of PI3K/AKT/mTOR Pathway." Cell Proliferation, vol. 53, no. 2, 2020, pp. e12739.
Zhou J, Jiang YY, Chen H, et al. Tanshinone I attenuates the malignant biological properties of ovarian cancer by inducing apoptosis and autophagy via the inactivation of PI3K/AKT/mTOR pathway. Cell Prolif. 2020;53(2):e12739.
Zhou, J., Jiang, Y. Y., Chen, H., Wu, Y. C., & Zhang, L. (2020). Tanshinone I attenuates the malignant biological properties of ovarian cancer by inducing apoptosis and autophagy via the inactivation of PI3K/AKT/mTOR pathway. Cell Proliferation, 53(2), e12739. https://doi.org/10.1111/cpr.12739
Zhou J, et al. Tanshinone I Attenuates the Malignant Biological Properties of Ovarian Cancer By Inducing Apoptosis and Autophagy Via the Inactivation of PI3K/AKT/mTOR Pathway. Cell Prolif. 2020;53(2):e12739. PubMed PMID: 31820522.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tanshinone I attenuates the malignant biological properties of ovarian cancer by inducing apoptosis and autophagy via the inactivation of PI3K/AKT/mTOR pathway. AU - Zhou,Jin, AU - Jiang,Yuan-Yuan, AU - Chen,Huan, AU - Wu,Yi-Chao, AU - Zhang,Li, Y1 - 2019/12/09/ PY - 2019/08/22/received PY - 2019/10/29/revised PY - 2019/11/06/accepted PY - 2019/12/11/pubmed PY - 2020/3/7/medline PY - 2019/12/11/entrez KW - AKT KW - Autophagy KW - PI3K KW - Tanshinone Ⅰ KW - apoptosis KW - mTOR KW - ovarian cancer SP - e12739 EP - e12739 JF - Cell proliferation JO - Cell Prolif VL - 53 IS - 2 N2 - OBJECTIVES: Tanshinone I (Tan-I) is one of the vital fatsoluble monomer components, which extracted from Chinese medicinal herb Salvia miltiorrhiza Bunge. It has been shown that Tan-I exhibited anti-tumour activities on different types of cancers. However, the underlying mechanisms by which Tan-Ⅰ regulates apoptosis and autophagy in ovarian cancer remain unclear. Thus, this study aimed to access the therapy effect of Tan-Ⅰ and the underlying mechanisms. METHODS: Ovarian cancer cells A2780 and ID-8 were treated with different concentrations of Tan-Ⅰ (0, 1.2, 2.4, 4.8 and 9.6 μg/mL) for 24 hours. The cell proliferation was analysed by CCK8 assay, EdU staining and clone formation assay. Apoptosis was assessed by the TUNEL assay and flow cytometry. The protein levels of apoptosis protein (Caspase-3), autophagy protein (Beclin1, ATG7, p62 and LC3II/LC3I) and PI3K/AKT/mTOR pathway were determined by Western blot. Autophagic vacuoles in cells were observed with LC3 dyeing using confocal fluorescent microscopy. Anti-tumour activity of Tan-Ⅰ was accessed by subcutaneous xeno-transplanted tumour model of human ovarian cancer in nude mice. The Ki67, Caspase-3 level and apoptosis level were analysed by immunohistochemistry and TUNEL staining. RESULTS: Tan-Ⅰ inhibited the proliferation of ovarian cancer cells A2780 and ID-8 in a dose-dependent manner, based on CCK8 assay, EdU staining and clone formation assay. In additional, Tan-Ⅰ induced cancer cell apoptosis and autophagy in a dose-dependent manner in ovarian cancer cells by TUNEL assay, flow cytometry and Western blot. Tan-Ⅰ significantly inhibited tumour growth by inducing cell apoptosis and autophagy. Mechanistically, Tan-Ⅰ activated apoptosis-associated protein Caspase-3 cleavage to promote cell apoptosis and inhibited PI3K/AKT/mTOR pathway to induce autophagy. CONCLUSIONS: This is the first evidence that Tan-Ⅰ induced apoptosis and promoted autophagy via the inactivation of PI3K/AKT/mTOR pathway on ovarian cancer and further inhibited tumour growth, which might be considered as effective strategy. SN - 1365-2184 UR - https://www.unboundmedicine.com/medline/citation/31820522/Tanshinone_I_attenuates_the_malignant_biological_properties_of_ovarian_cancer_by_inducing_apoptosis_and_autophagy_via_the_inactivation_of_PI3K/AKT/mTOR_pathway_ L2 - https://doi.org/10.1111/cpr.12739 DB - PRIME DP - Unbound Medicine ER -