# Geodiamolide A, a Marine Sponge Depsipeptide, Halts Proliferation and Triggers Cell Death in Squamous Cell Carcinoma (A431, NMSC) In Vitro

## TL;DR

Geodiamolide A, a compound from marine sponges, stops the growth and causes cell death in a type of skin cancer called squamous cell carcinoma.

## Contribution

Geodiamolide A is the first depsipeptide shown to target non-melanoma skin cancer cells.

## Key findings

- Geodiamolide A significantly reduced A431 cell viability with an IC50 of 368 nM.
- It caused a 46% reduction in cell count and G2/M phase cell cycle arrest.
- Evidence of apoptosis was observed, including DNA fragmentation and membrane damage.

## Abstract

Geodiamolides are depsipeptides previously isolated from marine sponges that are able to disrupt cytoskeleton microfilaments, inhibit cell migration and invasion, and reverse the malignant phenotype of human breast cancer cell lines to polarized spheroid-like structures. Such cytotoxicity to different cellular targets in breast cancer cells suggests that these molecules might also act in other cancer types such as non-melanoma skin cancer (NMSC), one of the cancer types with high incidence worldwide. Thus, the goal of this work was to study the effects of the marine sponge depsipeptides Geodiamolide A and H (Geo A and Geo H) in human squamous cell carcinoma (A431, NMSC) in order to investigate their effects on cell proliferation and cell death. While no significant statistical difference was observed after Geo H treatment, an expressive dose-dependent reduction in A431 cell viability (IC50 of 368 nM, MTT assay; p < 0.05) and proliferation pattern (real-time cell analysis assay) was shown after 48 h exposure with Geo A. The cell proliferation blockade was confirmed after 24 h of Geo A treatment at 500 nM, with a 46% (p < 0.0001) reduction in the total number of cells (cell counting) and G2/M phase cell cycle arrest. Other cytotoxic evidence such as DNA fragmentation, phosphatidylserine exposure (flow cytometry), and time-dependent plasma membrane damage (Trypan Blue) suggested cell death by apoptosis. Therefore, Geo A showed both cytostatic and cytotoxic effects on A431 cells. Taken together, these data point out Geo A as a promising therapeutic molecule for NMSC treatment and is the first depsipeptide (marine or terrestrial), to our knowledge, to target this type of cancer cell.