Ethnomedicinal Uses, Phytochemistry, and Anticancer Potentials of African Medicinal Fruits: A Comprehensive Review

**Background:** Cancer is a leading cause of death globally, with Africa facing a disproportionate burden: 5.7% of new cases and 7.2% of deaths worldwide, projected to double to 1.5 million new cases by 2040. In South Africa, approximately 108,168 new cancer cases and 56,802 deaths were reported in 2020. Conventional therapies (chemotherapy, radiotherapy, surgery) are limited by drug resistance, severe side effects (liver damage, cardiotoxicity, neurotoxicity), and poor access in low-income settings. Africa hosts over 5,400 documented medicinal plants, with 80% of the population relying on plant-based primary healthcare. Fruits, however, have been explored far less than roots and barks for anticancer properties. This review aims to comprehensively document the traditional uses, phytochemistry, and anticancer potentials of African medicinal fruits.

**Methods:** The authors conducted a literature search limited to 2008–2023 across Web of Science, PubMed, ScienceDirect, Scopus, SpringerLink, and Google Scholar. Search terms included 'anticancer', 'phytochemicals', 'traditional uses', and 'indigenous African fruits'. Initially, eight native Southern African fruits (Sclerocarya birrea, Dovyalis caffra, Parinari curatellifolia, Mimusops caffra, Carpobrotus edulis, Vangueria infausta, Harpephyllum caffrum, Carissa macrocarpa) were identified but lacked anticancer research. The scope was expanded to include both native and widely cultivated African fruits with documented anticancer studies, resulting in 12 fruits: Tribulus terrestris, Xanthium strumarium, Withania somnifera, Xylopia aethiopica, Abelmoschus esculentus, Carissa macrocarpa, Carpobrotus edulis, Syzygium cumini, Kigelia africana, Annona muricata, Persea americana, and Punica granatum.

**Key Results:** The review presents extensive in vitro and limited in vivo data on anticancer mechanisms: - **Tribulus terrestris:** Aqueous fruit extract induced G0/G1 arrest and apoptosis in HepG2 cells via cyclin E/cdk2 degradation, Bax/Bcl-2 modulation, MMP-2/MMP-9 inhibition, and NF-κB suppression. In a Swiss albino mouse skin papillomagenesis model, oral administration at 800 mg/kg body weight significantly reduced papilloma number and tumor burden while lengthening the average latent period. - **Xanthium strumarium:** Chloroform and methanol fruit extracts inhibited ATG4B proteolytic activity and autophagic flux. Isolated pentacyclic triterpenoids showed IC50 values ranging from 4.27 μM to >100 μM across cancer cell lines. Xanthanolides (xanthinosin, xanthatin) induced selective cytotoxicity against C6 rat glioma cells with less toxicity to normal HUVEC cells. - **Withania somnifera:** Methanolic unripe fruit extract showed IC50 of 95 μg/mL against HepG2 cells in dichloromethane fraction. A plant-based L-asparaginase enzyme (72 ± 0.5 kDa homodimer) demonstrated strong cytotoxicity against leukemia cells. - **Xylopia aethiopica:** Methanol fruit extract showed IC50 values of 3.91 μg/mL (CCRF-CEM leukemia), 6.86 μg/mL (MiaPaCa-2 pancreatic), and 7.4 μg/mL (CEM/ADR5000 multidrug-resistant). Isolated flavonoid 3,4′,5-trihydroxy-6″,6″-dimethylpyrano[2,3-γ]flavone showed IC50 from 2.61 μM (CCRF-CEM) to 18.60 μM (U87MG.ΔEGFR glioblastoma). - **Abelmoschus esculentus:** Lectin (AEL) induced selective cytotoxicity against MCF-7 cells via caspase-3/9 and p21 upregulation, and against U87MG glioblastoma cells (IC50 21 μg/mL) via G0/G1 arrest and ROS generation. - **Carissa macrocarpa:** Hydroethanolic fruit extract showed GI50 values of 57 μg/mL (NCI-H460), 66 μg/mL (HeLa), 109 μg/mL (MCF-7), and >400 μg/mL (HepG2) without toxicity to nontumor porcine liver cells. - **Syzygium cumini:** Fruit pulp extract (75% aqueous ethanol) showed IC50 of 59 μg/mL (A549 lung cancer) and 38 μg/mL (seeds). In vivo, seed hydroalcoholic extract at 125 mg/kg/day reduced skin papilloma incidence by 75% in Swiss albino mice. - **Kigelia africana:** Methanol fruit extract showed IC50 from 6.79 μg/mL (SW620 colon) to 91.32 μg/mL (HT-29). In a forestomach tumorigenesis model, oral administration at 2 mg/day resulted in 67% inhibition of tumor incidence and 76% reduction in tumor burden. - **Annona muricata:** Aqueous acetone fruit extract showed IC50 of 4.8 μg/mL against MDA-MB-468 breast cancer cells, with selective EGFR-overexpressing cell inhibition. In a xenograft mouse model, 200 mg/kg diet for 5 weeks inhibited tumor growth via EGFR/ERK pathway downregulation. - **Persea americana:** Multiple bioactive compounds (proanthocyanidins, aliphatic acetogenins, persenones) target proliferation, survival, migration, and apoptosis pathways. A case-control study associated higher avocado intake with reduced prostate cancer risk. - **Punica granatum:** The most clinically advanced fruit. In a phase II study, 8 ounces of pomegranate juice daily prolonged prostate-specific antigen doubling time from 15 to 54 months over 33 months, with a 23% increase in serum nitric oxide and reduced oxidative stress.

TOXICOLOGY DATA VARIED

many extracts showed LD50 >5000 mg/kg orally (e.g., S. birrea, D. caffra, P. curatellifolia), but some exhibited hepatotoxicity at high doses (e.g., X. strumarium, P. americana seeds).

**Clinical Implications:** The review highlights a critical gap: despite rich ethnomedicinal use, only Punica granatum has reached clinical trials for cancer. Most studies are in vitro, with limited in vivo validation and no systematic clinical translation. The authors emphasize that fruit extracts with multiple phytochemicals may offer superior anticancer efficacy compared to isolated compounds. Key barriers include inadequate standardization, safety data, quality control, and adulteration. Given Africa's cancer burden and limited access to conventional therapies, these fruits represent cost-effective, readily available potential treatments. The review calls for investment in systematic preclinical studies, rigorous toxicity assessments, and well-designed clinical trials to validate traditional claims and develop safe, effective anticancer therapeutics from African medicinal fruits.