Adaptive metabolic responses toward a low oxygen environment are essential to maintain rapid proliferation and are relevant for tumorigenesis. Reprogramming of core metabolism in tumors confers a selective growth advantage such as the ability to evade apoptosis and/or enhance cell proliferation and promotes tumor growth and progression. One of the mechanisms that contributes to tumor growth is the impairment of cancer cell metabolism. In this review, we outline the small-molecule inhibitors identified over the past decade in targeting cancer cell metabolism and the usage of some of these molecules in clinical trials.

Background Baeckea frutescens ( B. frutescens ) of the family Myrtaceae is a plant that has been used in traditional medicine. It is known to have antibacterial, antipyretic and cytoprotective properties. The objective of this study is to explore the mechanism of B. frutescens leaves extracts in eliminating breast cancer cells. Method B. frutescens leaves extracts were prepared using Soxhlet apparatus with solvents of different polarity. The selective cytotoxicity of these extracts at various concentrations (20 to 160 μg/ml) were tested using cell viability assay after 24, 48 and 72 h of treatment. The IC 50 value in human breast cancer (MCF-7 and MDA-MB-231) and mammary breast (MCF10A) cell lines were determined. Apoptotic study using AO/PI double staining was performed using fluorescent microscope. The glucose uptake was measured using 2-NBDG, a fluorescent glucose analogue. The phytochemical screening was performed for alkaloids, flavonoids, tannins, triterpenoids, and phenols. Results B. frutescens leaves extracts showed IC 50 value ranging from 10 -127μg/ml in MCF-7 cells after 72 h of treatment. Hexane extract had the lowest IC 50 value (10μg/ml), indicating its potent selective cytotoxic activity. Morphology of MCF-7 cells after treatment with B. frutescens extracts exhibited evidence of apoptosis that included membrane blebbing and chromatin condensation. In the glucose uptake assay, B. frutescens extracts suppressed glucose uptake in cancer cells as early as 24 h upon treatment. The inhibition was significantly lower compared to the positive control WZB117 at their respective IC 50 value after 72 h incubation. It was also shown that the glucose inhibition is selective towards cancer cells compared to normal cells. The phytochemical analysis of the extract using hexane as the solvent in particular gave similar quantities of tannin, triterpenoids, flavonoid and phenols. Presumably, these metabolites have a synergistic effect in the in vitro testing, producing the potent IC 50 value and subsequently cell death. Conclusion This study reports the potent selective cytotoxic effect of B. frutescens leaves hexane extract against MCF-7 cancer cells. B. frutescens extracts selectively suppressed cancer cells glucose uptake and subsequently induced cancer cell death. These findings suggest a new role of B. frutescens in cancer cell metabolism. Electronic supplementary material The online version of this article (10.1186/s12906-019-2628-z) contains supplementary material, which is available to authorized users.

Breast cancer is the leading cause of cancer death in women in over 100 countries worldwide and accounts for almost 1 in 4 cancer cases among women. Baeckea frutescens of the family Myrtaceae has been used in traditional medicine and is known to possess antibacterial, antipyretic, and cytoprotective properties. In this study, we investigated the role of Baeckea frutescens branches extracts against human breast cancer cells. Baeckea frutescens branches extracts were prepared using Soxhlet apparatus with solvents of different polarity. The selective cytotoxic activity and the glucose consumption rate of Baeckea frutescens branches extracts of various concentrations (20 to 160 ug/ml) at 24-, 48-, and 72-hour time points were studied using MTT and glucose uptake assay. The IC50 values in human breast cancer (MCF-7 and MDA-MB-231) and mammary breast (MCF10A) cell lines were determined. Apoptotic study using AO/PI double staining was performed using fluorescent microscopy. The glucose uptake was measured using 2-NBDG, a fluorescent glucose analogue. The phytochemical screening of major secondary metabolites in plants was performed. This study reports that Baeckea frutescens branches extracts showed potent selective cytotoxic activity against MCF-7 cells compared to MDA-MB-231 cells after 72 hours of treatment. Evidence of early apoptosis which includes membrane blebbing and chromatin condensation was observed after 72 hours of treatment with Baeckea frutescens branches extracts. Interestingly, for the glucose uptake assay, the inhibition was observed as early as 24 hours upon treatment. All Baeckea frutescens extracts showed the presence of major secondary metabolites such as tannin, triterpenoid, flavonoid, and phenol. However, alkaloid level was unable to be determined. The identification of Baeckea frutescens and its possible role in selectively inhibiting glucose consumption in breast cancer cells defines a new role of natural product that can be utilised as an effective agent that regulates metabolic reprogramming in breast cancer.