Fig. 8
ES2 (OCCC) and OVCAR3 (OSC) showed different adaptive capacities in a drug free environment which influences the response to carboplatin. a Non-selected ancestral and Normoxia selected ES2 cell lines showed an evolutionary trade-off when exposed to CoCl2 mimicked hypoxia, this situation is reverted by the presence of cysteine. CoCl2 mimicked hypoxia selected cells behave equally in the presence or absence of cysteine. Upon carboplatin exposure, all ES2 cells variants benefits from a protective effect of cysteine, decreasing the cytotoxicity of carboplatin. So, ES2 cells exhibited a higher adaptive capacity to CoCl2 mimicked hypoxia and cysteine which reflects in a better fitness to the carboplatin rich non-selective environment, being CoCl2 mimicked hypoxia selected the best fitted. b Non-selected ancestral and Normoxia selected OVCAR3 cell lines showed an evolutionary trade-off when exposed to CoCl2 mimicked hypoxia, cysteine only reverts this situation in Non-selected ancestral cells. Upon carboplatin exposure, all OVCAR3 cells variants benefit from a protective effect of cysteine, decreasing the cytotoxicity of carboplatin. OVCAR3 cells variants benefit from different grades of cysteine protection: Non-selected ancestral>CoCl2 mimicked hypoxia selected>Normoxia selected. So, OVCAR3 cells exhibited a lower adaptive capacity to CoCl2 mimicked hypoxia and cysteine which reflects in a worse fitness to the carboplatin rich non-selective environment, being Normoxia selected the worst fitted. Overall, ES2 cells have a higher metabolic plasticity than OVCAR3 cells. This fact can underlie the intrinsic resistance to carboplatin exhibited by ES2 cancer in clinics. White ellipses in ES2 cells represent vacuoles characteristic of clear cell carcinoma