Next Article in Journal
Mechanism of the Formation of Electronically Excited Species by Oxidative Metabolic Processes: Role of Reactive Oxygen Species
Previous Article in Journal
Halogen-Substituted Derivatives of Dictyostelium Differentiation-Inducing Factor-1 Suppress Serum-Induced Cell Migration of Human Breast Cancer MDA-MB-231 Cells in Vitro
Open AccessCommunication

Betulinic Acid Suppresses Ovarian Cancer Cell Proliferation through Induction of Apoptosis

1
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea
2
College of Korean Medicine, Gachon University, Seongnam 13120, Korea
3
Department of Obstetrics and Gynecology, University of Ulsan, Asan Medical Center, Seoul 05505, Korea
4
School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomolecules 2019, 9(7), 257; https://doi.org/10.3390/biom9070257
Received: 9 May 2019 / Revised: 30 May 2019 / Accepted: 2 June 2019 / Published: 3 July 2019
(This article belongs to the Section Natural and Bio-inspired Molecules)
Ovarian cancer is one of the leading causes of cancer deaths worldwide in women, and the most malignant cancer among the different gynecological cancers. In this study, we explored potentially anticancer compounds from Cornus walteri (Cornaceae), the MeOH extract of which has been reported to show considerable cytotoxicity against several cancer cell lines. Phytochemical investigations of the MeOH extract of the stem and stem bark of C. walteri by extensive application of chromatographic techniques resulted in the isolation of 14 compounds (114). The isolated compounds were evaluated for inhibitory effects on the viability of A2780 human ovarian carcinoma cells and the underlying molecular mechanisms were investigated. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was employed to assess the anticancer effects of compounds 114 on A2780 cells, which showed that compound 11 (betulinic acid) reduced the viability of these cells in a concentration-dependent manner and had an half maximal (50%) inhibitory concentration (IC50) of 44.47 μM at 24 h. Nuclear staining and image-based cytometric assay were carried out to detect the induction of apoptosis by betulinic acid. Betulinic acid significantly increased the condensation of nuclei and the percentage of apoptotic cells in a concentration-dependent manner in A2780 cells. Western blot analysis was performed to investigate the underlying mechanism of apoptosis. The results indicated that the expression levels of cleaved caspase-8, -3, -9, and Bax were increased in A2780 cells treated with betulinic acid, whereas those of Bcl-2 were decreased. Thus, we provide the experimental evidence that betulinic acid can induce apoptosis in A2780 cells through both mitochondria-dependent and -independent pathways and suggest the potential use of betulinic acid in the development of novel chemotherapeutics for ovarian cancer therapy. View Full-Text
Keywords: Cornus walteri; betulinic acid; ovarian cancer; apoptosis; mitochondria-dependent pathway; mitochondria-independent pathway Cornus walteri; betulinic acid; ovarian cancer; apoptosis; mitochondria-dependent pathway; mitochondria-independent pathway
Show Figures

Graphical abstract

MDPI and ACS Style

Lee, D.; Lee, S.R.; Kang, K.S.; Ko, Y.; Pang, C.; Yamabe, N.; Kim, K.H. Betulinic Acid Suppresses Ovarian Cancer Cell Proliferation through Induction of Apoptosis. Biomolecules 2019, 9, 257.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop