Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Costus speciosus J Koenig (Costaceae) exerts anti-proliferative effect on breast cancer cells via induction of cell cycle arrest and inhibition of activity of metalloproteinase-2

Nahed O Bawakid¹, Ahmed Abdel-Lateff^2,3, Fardous F El-Senduny⁴, Walied M Alarif⁵

¹Department of Chemistry, Faculty of Science; ²Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, PO Box 80260, Jeddah 21589, Saudi Arabia; ³Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519; ⁴Department of Chemistry, Faculty of Science, Mansoura University, Mansoura 35516, Egypt; ⁵Department of Marine Chemistry, Faculty of Marine Sciences, King Abdulaziz University, PO Box 80207, Jeddah 21589, Saudi Arabia.

For correspondence:- Walied Alarif Email:

Accepted: 18 June 2021 Published: 29 July 2021

Citation: Bawakid NO, Abdel-Lateff A, El-Senduny FF, Alarif WM. Costus speciosus J Koenig (Costaceae) exerts anti-proliferative effect on breast cancer cells via induction of cell cycle arrest and inhibition of activity of metalloproteinase-2. Trop J Pharm Res 2021; 20(7):1365-1372 doi: 10.4314/tjpr.v20i7.7

© 2021 The authors.
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Abstract

Purpose: To Investigate the antiproliferative effect of n-hexane-diethyl ether fraction of Costus speciosus (NP) on triple negative breast cancer (MDA-MB-231) cells, and the mechanism involved.

Methods: Maceration with methanol (CH₃OH) was used for extraction of Costus speciosus rhizomes. Chromatographic separation was used to obtain the non-polar fraction (NP) via elution with n-hexane:(C₂H₅)₂O at a volume ratio of 9:1. The cytotoxic effect of NP was evaluated against two breast cancer cell lines i.e., triple negative (MDA-MB-231) and positive ER (MCF-7) employing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT) assay, and the IC50 values were estimated. Cell cycle was determined with flow cytometry, while the likely mechanism involved in the cytotoxic effect was investigated using comet assay, immunofluorescence, clonogenic and scratch assays, zymography and detection of the antioxidant markers.

Results: NP produced potent cytotoxicity against MDA-MB-231, with IC₅₀ value of 4 ± 0.03 µg/mL, whereas its IC₅₀ for MCF-7 was 27 ± 1.3 µg/mL. It induced apoptosis via cell cycle arrest at G1 phase. Moreover, NP markedly decreased levels of superoxide dismutase (SOD), reduced glutathione (GSH), and matrix metalloprotease-2 (MMP-2), in MDA-MB-231 cells. Moreover, it inhibited cancer cell migration and colony formation.

Conclusion: Non-polar fraction of Costus speciosus (NP) exerted cytotoxic effect on triple negative breast cancer cells (MDA-MB-231) and positive ER (MCF-7). It inhibited cancer cell migration and colony formation. Interestingly, NP arrested the breast cancer cell cycles at sub-G1 phase, inhibited SOD and MMP-2, and decreased GSH levels. It induced apoptosis via DNA damage, downregulation of mutant p53, and over-expressions of the cell cycle inhibitors p21 and p27.

Keywords: Medicinal plants, Costus speciosus, anti-proliferation, MMP-2