###### Abstract  
Synthesis of gold nanoparticles (AuNPs) using phytochemicals has become tremendously prominent in biomedical applications because of its enhanced bioactivity and biocompatibility. In this study, water extracts from the leaves of _Cyclopia genistoides_ (_C. genistoides_), commonly known as honeybush (HB), were used to synthesize honeycomb gold nanoparticles (HB-AuNPs). The HB water extracts (HBE) served as both reducing and capping agents in the synthesis of HB-AuNPs. The HB-AuNPs were characterized by UV-Vis spectrophotometry, dynamic light scattering (DLS), and transmission electron microscopy (TEM). The cytotoxicity and apoptotic effects of the HBE and HB-AuNPs, alone and in combination with doxorubicin (Dox), were examined against various human cell lines. Spherical-shaped HB-AuNPs with a hydrodynamic diameter range of 63 to 121 nm were produced. The HB-AuNPs conferred selective cytotoxicity against colon (Caco-2), breast (MCF-7), and prostate (PC-3) cancer cells and did not display any cytotoxicity to non-cancerous skin fibroblast (KMST-6) and human embryonic kidney (HEK)-293 cells. Moreover, co-treatment of Caco-2 cells with HB-AuNPs and Dox (at non-toxic concentrations) significantly enhanced the anti-cancer effects of Dox towards the Caco-2 cells. Furthermore, it was demonstrated that HB-AuNPs induced PC-3 cell death through apoptosis. Further studies are warranted to elucidate the mechanisms by which the HB-AuNPs influence cell death when used alone or in combination with drugs, as well as the type of phytochemicals involved in AuNPs synthesis and activity. Cyclopia genistoides; gold nanoparticles; green synthesis; medicinal plants; phytochemicals; phytotherapy 22 February 202315 March 202315 March 202317 March 20  
(HB), of the genus _Cyclopia_, became a medicinal plant of interest as a mangiferin (MGF)-rich plant [4]. MGF has many health benefits [5] and is believed to be among the phytochemicals that are responsible for HB's bioactivity [4; 6]. _Cyclopia_ are classified into 20 species of flowering plants, examples include _C. intermedia_, _C. genistoides_, _C. maculata_, _C. sessiliflora_, and _C. longifolia_ that are endemic to the Cape Floristic Region of South Africa. HB leaves are commonly used to make medicinal beverages and a herbal tea [7; 8] that is caffeine-free and recognized for its many health benefits [4; 9; 10], such as anti-oxidant, anti-mutagenic, and anti-carcinogenic activities [8; 11; 12]. HB tea has been used by indigenous South African people for many centuries in folk medicine [7; 8] to treat various ailments such as respiratory infections and digestive problems, to soothe the central nervous system, and to boost the immune system [9]. It has also been reported to have the inherent ability to prevent the development of skin cancer [13; 14] and confer protection against oxidative stress via radical scavenging activity, iron-reducing potential, and inhibition of lipid peroxidation [7]. Although there is a notion that plant-derived medicines are safe, some of the phytochemicals are associated with serious health issues [15]. Moreover the pure active compounds tend to have low solubility, permeability, and bioavailability, which has limited their clinical application [16]. The emergence of green nanotechnology proved vital for phytotherapy, to help improve drug delivery, bioavailability, and reduce bystander effects. Nanotechnology deals with the synthesis and application of materials within a size range of 1 to 100 nm [16; 17; 18]. Among the various types of NPs, metallic NPs have drawn considerable attention due to their unique catalytic, optical, and electronic properties [18; 19; 20]. Generally, these NPs are synthesized by physical and chemical methods using top-down and bottom-up approaches. However, both these methods are potentially hazardous to the environment and living organisms, as they use toxic chemical additives and high temperatures [18; 19].