Anticancer potential of mangrove derived metabolites: cytotoxicity and phytochemical based studies

Mangroves are a rich source of bioactive phytochemicals that have substantial pharmacological potential, especially for the treatment of cancer. While scientific studies have confirmed the therapeutic properties and metabolite profiling of few mangrove species, other species, especially from the Rhizophoraceae family, remain relatively unexplored. This study investigates the anticancer activities, antimigratory potential and phytochemical constituents of methanolic extracts from six mangrove species, namely Rhizophora mucronata, Rhizophora apiculata, Bruguiera gymnorhiza, Bruguiera cylindrica, Kandelia candel and Ceriops tagal, which are representative species of the four genera of the Rhizophoraceae family. The cytotoxic potential of methanolic leaf extracts was assessed against non-small cell lung carcinoma (A549), oral squamous carcinoma (AW 13516), and cervical cancer (HeLa) cell lines using MTT assay, and the associated anti-migratory properties were monitored using the scratch wound healing assay. Toxicity against non-cancerous keratinocyte (HaCaT) cell line was also performed to assess the selectivity of the extracts. Liquid chromatography-high resolution mass spectrometry (Orbitrap-LC-HRMS) was used for the metabolite profiling of methanolic leaf extracts of selected mangroves species. The active constituents of B. cylindrica exhibited significant anticancer effects in comparison to the other methanolic extracts under study with IC₅₀ levels of 323.965 ± 1.417 µg/mL, 287.062 ± 1.127 µg/mL and 25.942 ± 2.048 µg/mL against A549, AW 13516, and HeLa cells respectively whereas no cytotoxicity was observed against normal cells (HaCaT). In addition, the results of the scratch wound healing assay on A549 cells underscored the anti-migratory potential of mangrove-derived extracts. LC-HRMS analysis of leaf extracts showed presence of 107 metabolites. Compounds with well-documented anticancer properties, such as chlorogenic acid, esculetin, phloroglucinol, caffeic acid, rutin, quercetin, naringenin, kaempferol, nobiletin, and luteolin were detected. Our study lays down a groundwork for B. cylindrica as a promising candidate for exploring mangrove-derived bioactive compounds as potential oncological drugs, having combined cytotoxic and anti-migratory effects, supporting the need for further study to elucidate their anticancer and potentiating mechanisms.