Effects of <em>Sutherlandia Frutescens</em> on Cancer and Primary Cells during Chemotherapy and Chemotherapy Induced Cellular Senescence
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Background/Objectives: Cancer is a global health problem. Chemotherapeutics such as 5-fluorouracil and etoposide are important but limited by side effects and resistance. Cel-lular senescence can both suppress and promote tumors through therapy-induced senes-cence (TIS) and the senescence-associated secretory phenotype (SASP). Sutherlandia fru-tescens (SF), used in African traditional medicine, may have anti-cancer effects. As the use of herbal medicine increases, understanding its interactions with chemotherapeutic agents—particularly on cellular responses and senescence—is crucial. In this study, the effect of SF and chamomile on cancer cells (CaCo-2, PANC-1) and human skin fibroblasts (HDF) during chemotherapy was investigated. Methods: Aqueous extracts of SF, and a commercially available product of SF capsules (Ballonerbse), and chamomile were tested for their antioxidant potential and physical properties. The cytotoxicity of chemotherapeutics and plant extracts was tested on cancer cells using XTT assay and confluence measurements. Senescence was induced in cancer cells and primary cells (HDF) by chemotherapy and subsequent treatment with plant ex-tracts. Cellular responses were assessed by microscopy, viability assays, IL-6 ELISA, flow cytometry and qPCR. Results: The chemotherapeutic agents inhibited cell growth, with the PANC-1 cells re-sponding more sensitively to etoposide. The SF extract supported cell recovery after etopo-side treatment. IL-6 secretion and cell cycle effects were cell line-specific. In HDFs, SF sig-nificantly influenced the SASP factors interleukin 6 and 8 as well as MMP1. in addition, SF led to a significant upregulation of SOD2. Conclusions: SF and chamomile extracts modulate chemotherapy-induced cellular re-sponses. In addition, SF is induces SASP factors in primary HDF cells, that could influ-ence the tumor milieu when rendered senescent as a byproduct of chemotherapy.