The Madagascar periwinkle (Catharanthus roseus) is a beautiful flower that grows on the island of Madagascar. It is one of the most important medicinal plants in the treatment of cancer and has saved thousands of children with lymphatic leukaemia. The Madagascar periwinkle is a great example of why biodiversity needs to be protected. It has grown in isolation on the island and developed genome mutations, creating secondary metabolic products that help the plant to survive in the Madagascar ecosystem. More than 200 alkaloid compounds are found in the Madagascar periwinkle, of which vincristine and vinblastine are used in medicinal treatments. Although new cancer drugs are constantly being developed, vincristine and vinblastine, or vinca alkaloids, are still important in medicine.
The biosynthesis, which is the enzyme-catalysed process in which simple compounds are converted into new compounds, of the Madagascar periwinkle was studied for years. The plant’s leaves have traditionally been used in Madagascar to lower blood sugar levels and control diabetes, as well as to treat infections and wounds. When Canadian researchers Robert Noble and Charles Beer started to investigate how the Madagascar periwinkle lowers blood sugar in the 1950s, they found something else interesting instead.
Noble and Beer gave rats flower extracts orally, but no effect on serum glucose levels was observed. The researchers tried a different approach, giving the rats the extract intravenously in the hope that it would boost the blood sugar lowering effect. This led to unexpected consequences: the rats died from bacterial infections. However, the researchers found that the extracts of the plant had an immunosuppressive effect, meaning a strong effect on white blood cells and bone marrow. This led to the discovery of anti-cancer properties in further research. Noble and Beer kept analysing Madagascar periwinkle substances until they identified the active compound, which they named vincaleukoblastine (vinblastine). Vinblastine interferes with intracellular metabolism and inhibits cell division, which means it is a chemotherapeutic agent.
Charles D. Carmichael and Harold P. S. Harington isolated vincristine from the Madagascar periwinkle in the 1950s. Carmichael and Harington worked for the Canadian Cancer Research Foundation, and their research focused on discovering anti-cancer agents in wild plants. Vincristine was one of the effective substances they found to prevent cancer cells from dividing.
At the same time, Gordon Svoboda and Irving Johnson at Eli Lilly and Company were studying plant samples from around the world in the hope of finding plant extracts that could be used to develop cancer drugs. They attended a conference where the Canadian researchers presented their research.
The researchers found they shared a common interest in the Madagascar periwinkle and started cooperation.
Svoboda and Irving studied the effect of vincristine on microtubule formation and cell division. Microtubules are important for many cellular functions, such as division, transport of materials and maintenance of cell structure. Cell cultures were treated with vincristine, which allowed the researchers to monitor the effects of vincristine under the microscope and assess its effectiveness in preventing cell division.
Vincristine and vinblastine are toxic to insects and herbivores. They are indole alkaloids that inhibit cell division and can paralyse or kill insects and herbivores if they eat the Madagascar periwinkle. In humans, the compounds have a different effect and have been shown to help the body fight cancer cells.
Most plant-based anti-cancer drugs target cell division in one way or another. This makes them effective in treating cancer. Because cancer cells divide uncontrollably, many drugs aim to prevent this process. Vincristine and vinblastine, and paclitaxel from the Pacific yew (Taxus brevifolia), target microtubules that form a part of the cytoskeleton. The cytoskeleton is made up of proteins called tubulin, which form long strands. Vincristine and vinblastine bind ß-tubulins and block the formation of strands, preventing cells from dividing normally. All three substances affect microtubule function, but in different ways. They inhibit the cell from dividing into the metaphase stage. In other words, affecting microtubules prevents tumour growth, if the drug makes the structure of the cancer cells unstable.
Vincristine is typically more effective in treating blood cancers such as acute lymphoblastic leukaemia. Vinblastine, on the other hand, has a better effect on solid tumours. It is used to treat Hodgkin lymphoma, non-Hodgkin lymphoma, breast cancer and testicular cancer.
“It is fascinating that molecules created by the process of mutual survival between plants and insects can influence human biological processes. In nature, an active chemical structure is no coincidence, but repurposing these rare molecules for new uses such as medicine requires innovation,” says Tommi Nyrönen, director of ELIXIR Node of Finland. Nyrönen has studied medicinal substances.
“Natural compounds that may be toxic to one species can, if properly dosed, help another species, as in the case of vinca alkaloids. What’s exciting is what we don’t yet know, because we don’t yet know all the microbes or plants on Earth yet. Similar discoveries can be made in the future by collecting and analysing molecular-level data from research in living nature.”
Information on vinca alkaloids can be found in many databases. For example, ChEMBL, BioStudies, UniProt and Reactome provide information on pharmacological properties, target proteins (such as tubulin), mechanisms, and cellular effects.
“ELIXIR is a data infrastructure on living nature. The databases are part of ELIXIR’s data repositories, which are freely available for scientific research, education and industry,” says Nyrönen.
ChEMBL (Chemical Database) is a chemical database that focuses specifically on the interaction between drugs and their target proteins. It allows for the examination of drugs’ biological effects and pharmacological profiles. The database contains information on drug efficacy, safety, and other biological responses.
Metabolism enables the body to transform active drug compounds into less active or more easily excretable forms. These chemical changes are often facilitated by cytochrome P450 enzymes. Drug metabolism affects how long a drug remains active in the body, how quickly it is eliminated, and how effective it is. If metabolism is slow, the drug may persist longer in the body, whereas rapid metabolism shortens its duration of action. Metabolic pathways can vary between individuals due to genetic factors, environmental influences, and interactions with other medications. As a result, two individuals may have different responses to the same drug.
A bioassay is an experimental method used to measure the potency or effectiveness of a substance, such as a drug, chemical, or natural product, based on its biological response. This is particularly important in drug development as it provides valuable insights into how a substance interacts within the body.
Search: The database allows users to search for specific compounds and their bioassay results, particularly assessing their effects on cytotoxicity or receptor responses. It also provides information on interactions between the queried substance and various drug compounds (drug matrix).
The BioStudies database serves as a central repository for storing descriptions of biological studies. It contains links to datasets stored in other databases, as well as data that do not fit existing structured archives. This allows for the storage of a wide variety of study types in a simple format.
ArrayExpress functioned as a database for functional genomics for over 20 years. In September 2022, its user interface was discontinued, and all data were transferred to BioStudies. This transition enhances data integration and accessibility for the research community.
Search: For example, when studying the effect of vincristine on cancer cell growth, BioStudies may contain experimental setups, analysis methods, and results that aid in interpretation.
A drug, such as vinblastine, can have multiple target proteins that it activates, inhibits, or modifies to achieve its biological effects. Drug target proteins can be involved in various biological processes and cell membranes across different organ systems, with their number varying depending on the drug’s structure and function.
UniProt (Universal Protein Resource) is the world’s leading high-quality, comprehensive, and freely available database of protein sequences and functions, maintained by the UniProt Consortium. It provides extensive and detailed information on protein structure, function, interactions, genetic backgrounds, and diseases.
The database is particularly useful in drug development and understanding drug mechanisms, as it helps map how drugs affect protein function. UniProt contains amino acid sequences of proteins, detailing their structures. It includes evolutionary information and species-specific variations. The database is linked to the Protein Data Bank (PDB), which provides three-dimensional structural insights into protein mechanisms and molecular interactions.
UniProt also provides data on how drugs bind to proteins and alter their function, which helps in understanding how drugs influence protein activity and vice versa. Additionally, it offers insights into the genes encoding these proteins, how gene regulation occurs, and how genetic mutations (e.g., through mutations) can impact protein function and contribute to diseases.
Search: The database can be used to investigate the interactions between tubulin proteins and vincristine and its effects on cell division.
The Reactome database focuses on cellular processes and signalling pathways. It is a manually curated database providing insights into biochemical reactions within cells and organs, including protein, RNA, and biomolecular interactions such as signalling pathways, metabolic pathways, and gene expression.
It also contains information on how disruptions in specific biological reactions can lead to diseases, making it valuable for drug development and biomarker discovery. Reactome offers visual pathway maps that depict molecular interactions within biological pathways. For example, vincristine’s effects can be linked to pathways involved in cell division regulation and apoptosis (programmed cell death).
Search: The database enables researchers to explore how vincristine affects different signalling pathways and its overall impact at the cellular level.
Ari Turunen
27.3.2025
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More information:
ELIXIR Core Data Resources
https://elixir-europe.org/platforms/data/core-data-resources
CSC – IT Center for Science
is a non-profit, state-owned company administered by the Ministry of Education and Culture. CSC maintains and develops the state-owned, centra- lised IT infrastructure.
https://research.csc.fi/cloud-computing
ELIXIR
builds infrastructure in support of the biological sector. It brings together the leading organisations of 21 Euro- pean countries and the EMBL European Molecular Biology Laboratory to form a common infrastructure for biological information. CSC – IT Center for Science is the Finnish centre within this infrastructure.
ELIXIR is partly funded by the European Commission