Ethnomedicinal versus random testing for antineoplastic activity; A review of South African indigenous and naturalised plants

• Most SA plants tested for anticancer activity lack traditional cancer use. • Indigenous anticancer plants are overlooked in new drug screening efforts. • Breast cancer cells are the primary target in most plant studies. • Aloe ferox shows strong activity (IC 50 0.48 µg/mL) against A375 melanoma cells. • Ethnomedicinal data boosts the chance of finding active species by >50 %. This review aims to consolidate published scientific literature on South African indigenous and naturalised medicinal plants used to treat cancer, including plant species used by traditional healers that have not yet been scientifically investigated. Moreover, literature on South African plants tested against cancer cell lines without any traditional anticancer use (random testing) is collated here. A literature search was conducted on scientific databases including Google Scholar, PubMed and ScienceDirect covering published English original research between 2000 and 2024. A total of 59 plant species were reportedly used to treat cancer, and a further 53 species have been screened for cytotoxic effects against cancer cells. Only 13 species (24.5 %) among those tested have a traditional use in cancer. Indigenous anticancer plants are often overlooked in the screening for new anticancer drugs. Of the 53 plant species tested for cytotoxicity against cancer cells, 23 (41.81 %) demonstrated an IC 50 value of ≤50 μg/mL and 7 of these plants are used traditionally to treat cancer in South Africa. Moreover, a lack of studies identifying the active compounds present in the most promising plant species is also highlighted. However, potential anticancer compounds linked to these plants are presented. The most intensively studied anticancer phytomolecules from a South African plant are the combretastatins, initially isolated from Combretum caffrum (Eckl. & Zeyh.) Kuntze (Combretaceae). This review highlights the lack of scientific investigation into traditionally used plants that are used for the treatment of cancer and therefore paves the way for future ethnomedicinal and cytotoxicity studies of South African medicinal plants that may lead to the development of novel anticancer drugs.