Neochloris sp. PA3, an Oligotrophic Desert Oasis Microalga, Exhibits Differential Cytotoxicity and Apoptosis-Associated Effects in Human Cancer Cells

Microalgae are increasingly recognized as valuable sources of natural products with potential applications in cancer prevention and therapy due to their ability to produce structurally diverse bioactive metabolites. In the present study, methanolic extracts from microalgal strains isolated from the oligotrophic desert oasis of the Cuatro Ciénegas Basin (Mexico) were evaluated for their antioxidant activity and in vitro cytotoxic effects against human breast (MCF7), colon (Caco2), prostate (DU145), leukemia (MOLT-4), and ovarian (OVCAR-3) cancer cell lines. The isolates were identified by rbcL gene sequencing and phylogenetic analysis as members of the genera Asterarcys, Chlorella, and Neochloris. Antioxidant properties were evaluated using complementary in vitro assays, whereas cytotoxicity was assessed using the MTT assay and apoptosis-associated cellular responses were investigated by morphological analysis, acridine orange/ethidium bromide staining, and measurement of executioner caspase-3/7 activity. Neochloris sp. PA3 showed the highest total antioxidant capacity and detectable ferrous ion-chelating activity, whereas Chlorella sp. PS exhibited the strongest superoxide radical scavenging activity. Among the evaluated strains, the methanolic extract of Neochloris sp. PA3 exhibited the most favorable overall antiproliferative profile, with IC50 values of 17.1, 19.0, and 19.1 µg/mL against MCF7, Caco2, and DU145 cells, respectively, while displaying markedly lower cytotoxicity toward the non-tumorigenic Vero and Detroit 548 cell lines, indicating differential cytotoxicity between the tested cancer and non-tumorigenic cell models. The extract induced time-dependent reductions in cell viability, morphological and nuclear alterations consistent with apoptotic cell death, and increased executioner caspase-3/7 activity. Collectively, these findings provide preliminary in vitro evidence of differential cytotoxicity and an apoptosis-associated cellular response in Neochloris sp. PA3-treated cancer cells.