Bioactive constituents of numerous marine organisms have been investigated recently for their preclinical and clinical anticancer activity. Three marine organisms: black-spotted sea cucumber: Pearsonothuria graeffei (Pg), lollyfish: Holothuria atra (Ha), and sea hare: Aplysia dactylomela (Ad), were collected during winter 2019 from Gulf of Aqaba, Red Sea, Egypt, and macerated with ethanol into three different extracts: PgE, HaE, and AdE, where each was in vitro assessed for its antiproliferative and proapoptotic properties on HepG2, HCT-116, and MCF-7 cancer cells. PgE dose-dependently inhibited the growth of HepG2, HCT-116, and MCF-7 cells within IC50 values 16.22, 13.34, and 18.09 μg/mL, respectively, while the IC50 values for the antiproliferative activity of HaE were 12.48, 10.45, and 10.36 μg/mL , respectively, and the IC50 values of AdE were 6.51, 5.33, and 6.87 μg/mL, respectively. All extracts were found to induce G0/G1 cell cycle arrest for HepG2 cells side by side with their inhibition of CDK2 on all three cell lines while all extracts were also showed to induce apoptosis in HepG2 cell line at pre-G1 phase supplemented by their anticancer activity via proapoptotic protein Bax, caspase-3, and cleavage PARP increase, and antiapoptotic protein Bcl-2 downturn. Moreover, necrosis has been relatively noticed in HepG2 cell line as an additional anticancer activity for each extract. Our data introduced three ethanolic marine extracts as natural chemotherapeutic agents to be further developed for cancer control.
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