Abstract
BackgroundAdaptive metabolic response towards a low oxygen environment is essential to maintain rapid tumour proliferation and progression. The vascular network that surrounds the tumour develops an intermittent hypoxic condition and stimulates hypoxia-inducing factors. Baeckea frutescens is used in traditional medicine and known to possess antibacterial and cytoprotective properties. In this study, the cytotoxic effect of B. frutescens leaves and branches extracts against hypoxic human breast cancer (MCF-7) was investigated.MethodThe extracts were prepared using Soxhlet apparatus for ethanol and hexane extracts while the water extracts were freeze-dried. In vitro cytotoxic activities of B. frutescens extracts of various concentrations (20 to 160 μg/mL) at 24, 48, and 72 hours time points were studied using MTT in chemically induced hypoxic condition and in 3-dimensional in vitro cell culture system. An initial characterisation of B. frutescens extracts was carried out using Fourier-transform Infrared- Attenuated Total Reflection (FTIR-ATR) to determine the presence of functional groups.ResultsAll leaf extracts except for water showed IC50 values ranging from 23 -158 μg/mL. Hexane extract showed the lowest IC50 value (23 μg/mL), indicating its potent cytotoxic activity. Among the branch extracts, only the 70% ethanolic extract (B70) showed an IC50 value. The hexane leaf extract tested on 3- dimensional cultured cells showed an IC50 value of 17.2 μg/mL. The FTIR-ATR spectroscopy analysis identified various characteristic peak values with different functional groups such as alcohol, alkenes, alkynes, carbonyl, aromatic rings, ethers, ester, and carboxylic acids. Interestingly, the FTIR-ATR spectra report a complex and unique profile of the hexane extract, which warrants further investigation.ConclusionAdaptation of tumour cells to hypoxia significantly contributes to the aggressiveness and chemoresistance of different tumours. The identification of B. frutescens and its possible role in eliminating breast cancer cells in hypoxic conditions defines a new role of natural product that can be utilised as an effective agent that regulates metabolic reprogramming in breast cancer.
Highlights
It is estimated that 18.1 million new cases and 9.6 million cancer deaths worldwide in 2018 and breast cancer is being the most commonly diagnosed and leading cause of death among females [1]
The identification of B. frutescens and its possible role in eliminating breast cancer cells in hypoxic conditions defines a new role of natural product that can be utilised as an effective agent that regulates metabolic reprogramming in breast cancer
The stabilization of hypoxia-inducing factor (HIF) is a hallmark of hypoxia and results in global transcriptional changes in gene expression, including genes with roles in promoting tumour progression, angiogenesis, metastasis, iron metabolism, glucose metabolism, cell proliferation and survival [27, 28]
Summary
It is estimated that 18.1 million new cases and 9.6 million cancer deaths worldwide in 2018 and breast cancer is being the most commonly diagnosed and leading cause of death among females [1]. Metastatic progression in tumorigenesis is initiated by genes involved in energy production, angiogenesis, tissue remodelling, enhance cell motility, matrix degradation, and epithelial-to-mesenchymal transition [5]. These genes trigger low aggressive cancer cells to invade surrounding tissues, attract supportive stroma, disperse cancer cells, and infiltrate distant metastatic niches [3]. Hyper-proliferative cancer cells outgrow their surrounding vascular network developing an intermittent hypoxic condition and stimulate hypoxia-inducing factor (HIF) [6]. The vascular network that surrounds the tumour develops an intermittent hypoxic condition and stimulates hypoxia-inducing factors. The cytotoxic effect of B. frutescens leaves and branches extracts against hypoxic human breast cancer (MCF-7) was investigated
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
