Integrative Evaluation of Kigelia africana Fruit Extract: Broad-Spectrum Anticancer Activity, Synergism with Cisplatin and Mechanistic Insights in Colorectal Carcinoma

<i>Kigelia africana</i> ("sausage tree") is an established medicinal plant in African traditional medicine, now recognized for its diverse bioactive constituents and emerging anticancer potential. This study systematically evaluates <i>Kigelia africana</i> fruit extract (KAE) in an in vitro model of HT-29 colorectal carcinoma cells, focusing on its cytotoxic effects, mechanistic impact on protein expression, and synergy with cisplatin chemotherapy. Across 42 oncology-related proteins, covering cell survival, apoptosis, adhesion, invasion, and signaling, KAE demonstrated extensive but typically moderate modulation, while cisplatin produced more pronounced responses in most markers. Protein changes linked to metastasis, therapy resistance, and survival were broadly suppressed, indicating significant antitumor activity. Notably, co-treatment with KAE and cisplatin in HT-29 cells resulted in marked synergistic cytotoxicity, permitting lower cisplatin doses while maintaining efficacy. LC-HRMS analyses revealed 14 metabolites in the extract, including phenolic acids naphthoquinones and iridoids, which may contribute to these effects.