Glioblastoma multiforme is one of the most lethal cancers known to medicine. It invades healthy brain tissue with such ferocity that complete surgical removal is nearly impossible. Even with surgery, radiotherapy and chemotherapy, survival rates remain alarmingly low. On average, patients live for around 15 months after diagnosis, and fewer than 5 per cent survive beyond five years. Recurrence is almost inevitable, and existing drugs often cause severe side effects and toxicity.
Researchers around the world have long sought alternative approaches to treating glioblastoma, with many turning their attention to nature’s vast chemical library. Plants have evolved intricate biochemical defences, many of which have been successfully adapted into modern cancer therapies. Now, a team of South African scientists has identified several flowering plants that may provide new leads for developing safer and more effective treatments.
An African discovery with global significance
The study, titled Investigating the antiproliferative properties of Amaryllidaceae plant species and their bioactive compounds on brain tumour cell lines, was published in Advances in Traditional Medicine . Led by Dr Sylvester I. Omoruyi of the School of Anatomical Sciences at the University of the Witwatersrand , the research was conducted in collaboration with Stellenbosch University, the South African Medical Research Council, and the Cape Peninsula University of Technology .
The researchers focused on three members of the Amaryllidaceae family: Crossyne flava, Amaryllis belladonna, and Boophone haemanthoides. These bulbous plants are widely distributed across southern Africa and have long been used in traditional medicine to treat various ailments, including inflammation, infections and pain. Previous studies have hinted at their neuroprotective and anticancer properties, but their effects on brain tumours had not been fully explored until now.
Our aim was to evaluate whether these plants and their bioactive compounds could selectively target glioblastoma cells without harming normal cells.
– Sylvester I. Omoruyi
This approach reflects a growing trend in cancer pharmacology: identifying natural substances that attack tumours while sparing healthy tissue, thereby reducing toxicity and improving patient outcomes.
Striking results from the Amaryllidaceae family
All three plant extracts significantly reduced the viability of glioblastoma cells, with effects that were largely dose-dependent. Among the species tested, Amaryllis belladonna showed the strongest antiproliferative activity, recording IC50 values as low as 4.55 µg/mL against the U251 cell line. Importantly, the extracts demonstrated selectivity, meaning they were more toxic to cancer cells than to normal heart cells.
In contrast, the isolated compounds were potent but less selective. For instance, 1α,3α-diacetylnerbowdine and distichamine displayed strong cytotoxicity but also affected non-cancerous cells, limiting their direct therapeutic use in their current form. Nonetheless, these compounds provide valuable chemical scaffolds for future drug design.
The study also revealed that the extracts inhibited ATP production in glioblastoma cells, suggesting a disruption of mitochondrial energy metabolism. Since cancer cells have abnormally high energy demands to sustain their rapid growth, this mechanism could be particularly effective in starving tumours of the energy they require. However, apoptosis – a common pathway for programmed cell death – was only triggered by the pure compounds and not by the crude plant extracts. This suggests that different mechanisms of cell death may be involved, a subject that the authors propose for further investigation.
A closer look at energy disruption
One of the most intriguing aspects of this research lies in its focus on energy metabolism. Glioblastoma cells are known for their metabolic reprogramming, often relying on glycolysis rather than oxidative phosphorylation, even when oxygen is abundant. This phenomenon, known as the Warburg effect, enables tumour cells to proliferate rapidly while evading cell death.
By reducing intracellular ATP levels, the Amaryllidaceae extracts appear to target this metabolic vulnerability. Similar effects have been observed in studies of other natural products, where compounds inhibit mitochondrial enzymes such as NADH-ubiquinone reductase or cytochrome c oxidase. Although the precise molecular targets remain unknown, Dr Omoruyi’s team demonstrated that treated cancer cells exhibited marked decreases in ATP levels and visible morphological changes such as cell shrinkage and loss of projections, hallmarks of disrupted metabolism and cellular stress.
Selectivity and the road to safer therapies
One of the most pressing challenges in oncology is achieving high selectivity for cancer cells while minimising harm to healthy tissue. Many standard drugs, including cisplatin, exhibit significant toxicity to the heart, kidneys and other organs. In this study, the extracts of Crossyne flava, Amaryllis belladonna and Boophone haemanthoides achieved selectivity indices greater than two, indicating preferential targeting of cancer cells over normal cardiac cells.
This is particularly encouraging given that cardiotoxicity remains a major concern in chemotherapy. The authors suggest that while the pure compounds may require structural modification to enhance selectivity, the crude extracts already show promise as natural cytotoxic agents that could be refined through further purification and formulation studies.
Why plant-based medicine matters
The use of medicinal plants in healthcare is far from new. Across Africa, approximately 75 to 90 per cent of the population still relies on traditional herbal medicine for primary healthcare. Many modern drugs, including the anticancer agents vincristine and paclitaxel, originated from plant sources. The Amaryllidaceae family itself has previously yielded galantamine, an alkaloid approved by the US Food and Drug Administration for the treatment of Alzheimer’s disease.
This new research reinforces the scientific value of ethnobotanical knowledge and highlights the global potential of African flora. By integrating traditional wisdom with molecular biology and pharmacology, scientists are uncovering powerful new tools for modern medicine. As Dr Omoruyi and his co-authors point out, there remains an “urgent unmet need” for affordable, accessible and effective treatments for glioblastoma, particularly in regions where advanced therapies are scarce or prohibitively expensive.
The next frontier: From lab to clinic
Although the study provides convincing in vitro evidence, clinical application is still a long way off. Future work will require testing in patient-derived cellular models and organoids, animal models to assess safety, efficacy and bioavailability, followed by carefully controlled clinical trials. Nevertheless, the results mark an important step in the quest for novel anticancer compounds from natural sources.
The research team envisions the possibility of synthesising analogues of these alkaloids or incorporating them into nanoparticle-based delivery systems that target brain tumours more precisely. Such approaches could overcome the challenge of the blood-brain barrier, which often prevents many promising compounds from reaching their intended site of action.
Cultivating hope in the fight against cancer
The identification of antiproliferative compounds from the Amaryllidaceae family represents a promising frontier in glioblastoma research. These findings suggest that Africa’s native flora could provide valuable chemical templates for the development of next-generation cancer therapeutics.
While much remains to be done before such compounds reach the clinic, the message is clear: nature continues to inspire medicine in unexpected and powerful ways. As the global search for more effective and less toxic cancer treatments continues, studies like this remind us that the answers may lie, quite literally, in our own back gardens.
Reference
Omoruyi, S. I., Augustine, T. N., Mabasa, L., Hussein, A. A., & Mavumengwana, V. (2025). Investigating the antiproliferative properties of Amaryllidaceae plant species and their bioactive compounds on brain tumour cell lines. Advances in Traditional Medicine, 25(787–799). https://doi.org/10.1007/s13596-025-00818-w
