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Cancer cells are refractory to most forms of chemotherapy. Conventional and alternative drugs, such as herbal extracts, have been developed to target cancer cells. This study aims to test the cytotoxic effects of Pelargonium endlicherianum root extracts on prostate cancer cells. In vitro cytotoxic activities of the methanolic and ethanolic root extracts (0–150 µg/mL) were screened against androgen dependent independent (PC-3) prostate cancer cell lines by MTT assay. Ethanolic root extract induced a significant decrease in cell viability characterized by 100 < IC50 < 150 µg/mL. The results of this study support the efficacy of P. endlicherianum as an anticancer agent for prostate cancer and a potential adjuvant treatment to current chemotherapeutic agents used in the treatment of prostate tumors. Further studies of the effects of individual flavonoids alone and in combination with each other and with currently used …