Enhancing the in vitro anticancer efficacy of Paclitaxel against triple-negative breast cancer via an exopolysaccharide from a haloalkaliphilic archaeal strain

Exopolysaccharides (EPSs) produced by haloalkaliphilic archaea exhibit unique properties contributing to varied industrial and medicinal applications. This study explored the anticancer therapeutic potential of an EPS derived from a haloalkaliphilic archaeal strain, which has not been previously isolated from solar salterns on the northwestern Mediterranean Egyptian coast. The selected isolate was identified as Natrialba chahannaoensis BG8. A Plackett-Burman (PB) fractional factorial design determined NaCl as the only significant variable positively affecting EPS production. The partially purified EPS analytical characterization revealed a carbohydrate content of 75.16 ± 2.1%, with Fourier transform infrared (FT-IR) spectroscopy; moreover, GC-MS suggested a heteropolysaccharide nature. For the first time, a neutral red uptake (NRU) assay revealed the anticancer effect of EPS against multiple human cancerous cell lines; A-431 epidermoid cancer (IC₅₀= 8.8 mg/mL), MCF-7 breast cancer (IC₅₀= 12.7 mg/mL), MDA-MB-231 triple-negative breast cancer (TNBC) (IC₅₀= 9.4 mg/mL), and HCT-116 colorectal cancer (IC₅₀= 10.4 mg/mL) cells. Additionally, EPS exhibited previously reported anti-hepatoblastoma activity against HepG-2 cells (IC₅₀= 21.2 mg/mL). The cell cycle analysis results suggested that the antiproliferative effect on MDA-MB-231 cells occurred through S phase arrest. Notably, synergistic interactions between EPS and the anticancer drug paclitaxel (PXL) were recorded in MDA-MB-231 cells via the Chou‒Talalay approach. Furthermore, an unpaired Student's t test disclosed that EPS induced a significant rise in the apoptosis marker caspase-3 (casp-3). This increase was higher than PXL alone and combined with EPS. However, the combined treatment exceeded PXL in significantly reducing MDA-MB-231 cells' migratory potentials, as evidenced by wound healing and matrix metalloproteinase-9 (MMP-9) determination assays. It also reduced the levels of the oxidative stress marker malondialdehyde (MDA). The EPS of N. chahannaoensis BG8 displayed a pro-apoptotic action against the TNBC cells MDA-MB-231, surpassing that of PXL. Furthermore, PXL-EPS combination reduced PXL-associated toxicity and increased metastasis control. These findings put EPS as a recommended safe complementary therapy, more effective than PXL monotherapy.