# Bioactivity-Guided Fractionation, Characterization, and Mechanistic Insights of Anticancer Agents from Simarouba glauca DC. Leaves

## TL;DR

This study explores the anticancer potential of Simarouba glauca leaf extracts, particularly hexane extract, against oral and other cancers, revealing multiple mechanisms of action.

## Contribution

The study identifies hexane extract of Simarouba glauca as a multi-target anticancer agent with synergistic bioactive compounds.

## Key findings

- Hexane extract of S. glauca showed potent anticancer activity against OSCC, cervical, and mammary cancer cell lines.
- D-erythro-Sphinganine was identified as a major constituent, but synergistic effects of multiple compounds are likely.
- Hexane extract altered cell cycle, triggered apoptosis, and inhibited migration in CAL-27 cells.

## Abstract

Although Simarouba glauca DC. has been recognized for its therapeutic properties, its anticancer effects against oral cancer have not been adequately investigated. The present study aimed to evaluate the activity of S. glauca leaf extracts against oral squamous cell carcinoma (OSCC). S. glauca leaves were extracted using solvents of increasing polarity, and the resulting fractions were evaluated for their phytochemical composition, antioxidant activity, and cytotoxic effects. Among all extracts, the S. glauca hexane extract (SGHE) exhibited the most potent anticancer activity against cell lines representing OSCC (CAL-27), cervical cancer (HeLa), and mouse mammary tumors (4T1). Bioactivity-guided fractionation identified D-erythro-Sphinganine as a major constituent present in hexane extract, possibly contributing to anticancer activity. But since the anticancer activity of crude hexane extract is superior compared to isolated D-erythro-Sphinganine, we predict a synergistic interaction among the multiple bioactive compounds present in the crude hexane extract. Hence, further studies were carried out with crude hexane extract. Mechanistic studies have shown that the anticancer activity of hexane extract is due to its ability to (a) alter cell cycle progression, (b) trigger apoptosis, and (c) inhibit cell migration in CAL-27 cells. Overall, these findings indicate that the hexane extract of S. glauca leaf possesses multi-target anticancer potential and warrants further mechanistic and in vivo investigations.