Natural compound Alternol exerts a broad anti-cancer spectrum and a superior therapeutic safety index .

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

Methods: 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.

Results: Our results showed that Alternol exerted a potent anti-cancer effect on 50 (83%) cancer cell lines with a GI 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.

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