Bursatella leachii purple ink secretion extract exerts cytotoxic properties against human hepatocarcinoma cell line (HepG2): In vitro and in silico studies

Liver cancer is the third leading cause of cancer death worldwide. Marine mollusc-derived extracts have gained attention as new potential natural-based anticancer agents to overcome the side effects caused by conventional chemotherapeutic drugs during cancer therapy. We evaluated the cytotoxic effects of a crude extract from the purple-ink released by the sea hare named Bursatella leachii (B. leachii) against human hepatocarcinoma cell line (HepG2) and explored the underlying mechanisms causing the programmed cell death (i.e., apoptosis). Expression of cleaved-caspase-8 and cleaved-caspase-3, key cysteine-aspartic proteases involved in the initiation and completion of the apoptosis process, appeared after HepG2 cell exposure to B. leachii extract. Gene expression levels of pro-apoptotic BAX, tumour suppressor TP53 and Cyclin D1 were increased after treatment with B. leachii. Using liquid chromatography-mass spectrometry, the main biomolecules in the B. leachii extract were identified as hectochlorin, malyngamide X, malyngamide S, bursatellin, and lyngbyatoxin A. Applying in silico approaches, the high scores predicted bioactivities for the five compounds were protease and kinase inhibitors. The ADME and cytochrome profiles for the compounds were also predicted. Altogether, the cytotoxic B. leachii extract presents high pro-apoptotic potentials, suggesting it as a promising safe natural product-based drug for the treatment of liver cancer.