# Natural compound Alternol exerts a broad anti-cancer spectrum and a superior therapeutic safety index in vivo

## TL;DR

Alternol, a natural compound, shows strong anti-cancer effects across many cancer types and is safe in animal models.

## Contribution

Alternol demonstrates a broad anti-cancer spectrum and a high therapeutic safety index in vivo.

## Key findings

- Alternol showed potent anti-cancer effects in 83% of 50 cancer cell lines with GI50 < 5 µM.
- It induced lethal responses in 24% of those cell lines at 10 µM concentration.
- Alternol had a high therapeutic index of 13.3 and an MTD of 665 mg/kg in mice.

## Abstract

Alternol is a natural compound isolated from the fermentation of a mutated fungus. We have demonstrated its potent anti-cancer effect via the accumulation of radical oxygen species (ROS) in prostate cancer cells in vitro and in vivo. In this study, we tested its anti-cancer spectrum in multiple platforms.

We first tested its anti-cancer spectrum using the National Cancer Institute-60 (NCI-60) screening, a protein quantitation-based assay. CellTiter-Glo screening was utilized for ovarian cancer cell lines. Cell cycle distribution was analyzed using flow cytometry. Xenograft models in nude mice were used to assess anti-cancer effect. Healthy mice were tested for the acuate systemic toxicity.

Our results showed that Alternol exerted a potent anti-cancer effect on 50 (83%) cancer cell lines with a GI50 less than 5 µM and induced a lethal response in 12 (24%) of those 50 responding cell lines at 10 µM concentration. Consistently, Alternol displayed a similar anti-cancer effect on 14 ovarian cancer cell lines in an ATP quantitation-based assay. Most interestingly, Alternol showed an excellent safety profile with a maximum tolerance dose (MTD) at 665 mg/kg bodyweight in mice. Its therapeutic index was calculated as 13.3 based on the effective tumor-suppressing doses from HeLa and PC-3 cell-derived xenograft models.

Taken together, Alternol has a broad anti-cancer spectrum with a safe therapeutic index in vivo.