Anticancer activity of Elaphoglossum paleaceum (Hook. & Grev.) sledge derived phloroglucinols in human hepatocellular carcinoma cells through potential transcriptional modulation of microRNAs

Abstract

Phloroglucinols derivatives are an important class of secondary metabolites widely distributed in Pteridophytes of the genera Elaphoglossum that exhibit multiple biological activities, including anticancer activity. Recent evidence suggests that many phytochemicals, including polyphenols, can significantly alter microRNA (miRNAs) expression profiles. miRNAs are short non-coding RNAs that can act as tumor suppressors or onco-miRNAs regulating the expression of cancer-associated genes post-transcriptionally, therefore, modulating cancer progression. Elaphoglossum paleaceum (Hook. & Grev.) Sledge phloroglucinols derivatives have demonstrated cytotoxic activity against several cancer models. Nevertheless, its relative mechanism of action and its effect on HCC cells have not still investigated. The present study aimed to evaluate the anticancer activity of hexanic/chloroformic extract of E. paleaceum and investigate its mechanism(s) of action on tumor suppressor and onco-miRNAs expression involved in HCC carcinogenesis. E. paleaceum hexanic/chloroformic extract exhibited cytotoxicity against HepG2 cells. Moreover, an E. paleaceum hexanic/chloroformic extract concentration approximating the IC50 induced upregulation of tumor suppressors miR-200b-5p, miR-34-5p, Let-7b-5p, and miR-218b-5p. These modulatory effects might contribute to inhibiting HepG2 cell growth observed after treatment with E. paleaceum hexanic/chloroformic extract. These data demonstrate the ability of E. paleaceum phloroglucinols derivatives to impede hepatocellular carcinoma cell proliferation, possibly by modulating critical miRNAs and consequently their downstream targets, suggesting a novel mechanism of the anticancer potential of phloroglucinols derivatives and positioning them as potential novel anticancer agents.