Oscillatoxins E (1) and F (2) are cyanotoxins isolated from cyanobacteria in the genus Lyngbya. We recently reported the first total synthesis of these compounds and determined their cytotoxicity in various cancer cell lines. Their anti-proliferative activities were moderate, but 2 exhibited unique cell line selectivity. In order to understand their mode of action, in this study we evaluated the cytotoxicity of 1 and 2 under nutrient-depletion culture conditions. Interestingly, 2 exhibited stronger cytotoxicity in HHUA endometrial cancer cells, especially under FBS-starvation conditions. However, its toxicity was not increased in HHUA cells precultured in FBS-depleted medium. These results suggest that 2 is not selectively toxic to nutrient-starved cells and that FBS components such as albumin more strongly neutralized the cytotoxicity of 2 relative to 1. The protein composition of FBS varies by production lot, and the amount of FBS supplemented to culture medium is flexibly determined depending upon the cell line used and experimental objectives. Therefore, it is important to consider the detoxification activity of FBS to precisely evaluate the properties of oscillatoxins, including cytotoxic potency, cell line selectivity, and their respective structure–activity relationships.