Kelussia odoratissima Mozaff. activates intrinsic pathway of apoptosis in breast cancer cells associated with S phase cell cycle arrest via involvement of p21/p27 in vitro and in vivo

Karimian, H. and Arya, Aditya and Fadaeinasab, M. and Razavi, M. and Hajrezaei, M. and Khan, A.K. and Ali, Hapipah Mohd and Abdulla, Mahmood Ameen and Noordin, M.I. (2017) Kelussia odoratissima Mozaff. activates intrinsic pathway of apoptosis in breast cancer cells associated with S phase cell cycle arrest via involvement of p21/p27 in vitro and in vivo. Drug Design, Development and Therapy, 11. pp. 337-350. ISSN 1177-8881, DOI https://doi.org/10.2147/DDDT.S121518.

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Official URL: http://dx.doi.org/10.2147/DDDT.S121518

Abstract

Background: The aim of this study was to evaluate the anticancer potential of Kelussia odoratissima. Several in vitro and in vivo biological assays were applied to explore the direct effect of an extract and bioactive compound of this plant against breast cancer cells and its possible mechanism of action. Materials and methods: K. odoratissima methanol extract (KME) was prepared, and MTT assay was used to evaluate the cytotoxicity. To identify the cytotoxic compound, a bioassay-guided investigation was performed on methanol extract. 8-Hydroxy-ar-turmerone was isolated as a bioactive compound. In vivo study was performed in the breast cancer rat model. LA7 cell line was used to induce the breast tumor. Histopathological and expression changes of PCNA, Bcl-2, Bax, p27 and p21 and caspase-3 were examined. The induction of apoptosis was tested using Annexin V-fluorescein isothiocyanate (FITC) assay. To confirm the intrinsic pathway of apoptosis, caspase-7 and caspase-9 assays were utilized. In addition, cell cycle arrest was evaluated. Results: Our results demonstrated that K. odoratissima has an obvious effect on the arrest of proliferation of cancer cells. It induced apoptosis, transduced the cell death signals, decreased the threshold of mitochondrial membrane potential (MMP), upregulated Bax and downregulated Bcl-2. Conclusion: This study demonstrated that K. odoratissima exhibits antitumor activity against breast cancer cells via cell death and cell cycle arrest.

Item Type: Article
Funders: UNSPECIFIED
Uncontrolled Keywords: Kelussia odoratissima; apoptosis; intrinsic pathway; MCF7; chemoprevention; breast cancer
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 06 Sep 2018 02:54
Last Modified: 30 Jan 2019 01:43
URI: http://eprints.um.edu.my/id/eprint/19145

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