An in vitro high-throughput assay for screening reproductive and toxic effects of anticancer compounds

Area of Science:

• Pharmacology
• Cell Biology
• Endocrinology

Background:

• Choriocarcinoma cell lines are valuable models for studying hormone synthesis and drug effects.
• Assessing drug candidates requires methods that evaluate cytotoxicity and specific cellular functions simultaneously.

Purpose of the Study:

• To develop and optimize an in vitro assay for evaluating anticancer drug candidates.
• To assess the impact of a marine mollusc extract on cytotoxicity, progesterone synthesis, and human chorionic gonadotropin (hCG) responsiveness in JAr cells.

Main Methods:

• Optimization of JAr cell culture conditions.
• Development of a 1H thiazolyl blue tetrazolium bromide assay for cytotoxicity assessment.
• Exposure of cells to a marine mollusc extract with and without hCG to measure progesterone (P4) synthesis and cell viability.

Main Results:

• The assay demonstrated acceptable intra- and interassay coefficients of variation (11.3% and 10.9%).
• Human chorionic gonadotropin (hCG) significantly increased progesterone (P4) synthesis.
• The mollusc extract reduced cell viability and exhibited complex dose-dependent effects on P4 synthesis, with interactions observed with hCG.

Conclusions:

• The optimized in vitro assay is a robust tool for characterizing novel drug effects on cytotoxicity and hormone production.
• This assay can differentiate between basal and gonadotropin-stimulated hormone synthesis.
• The findings support the utility of this assay for preclinical drug development and informing in vivo studies.