Roundup® Original DI promotes proliferation in papillary thyroid carcinoma cells: a comparative study highlighting cell-type-dependent effects.

INTRODUCTION

Glyphosate-based herbicides (GBHs), such as Roundup®, are ubiquitous environmental contaminants with emerging endocrine-disrupting properties. Based on previous findings of non-monotonic effects in thyroid models, this study investigated lineage-dependent cytotoxic and proliferative responses to Roundup® in thyroid cells with different cytogenic profiles.

METHODS

Human papillary carcinoma (BCPAP, BRAFV600E) and anaplastic carcinoma (8505C) cells were exposed to Roundup® Original DI (6.5-6500 µg/L) for 24 and 48 hours. Cell viability was assessed using trypan blue exclusion and CCK-8 assays, and proliferation was measured by BrdU incorporation. The data were integrated with previous results from normal (Nthy-ori 3-1) and papillary (TPC-1) cell lines for comparative analysis.

RESULTS

Exposure to Roundup® induced specific effects for each cell type. The BCPAP cell line demonstrated significant sensitivity, with reduced viability and sustained proliferative stimulation at low concentrations. In contrast, anaplastic 8505C cells proved to be highly resistant, exhibiting transient biphasic proliferation and recovery of viability even at high doses. A consolidated analysis established a clear hierarchy of sensitivity: TPC-1 > BCPAP > Nthy-ori3-1 > 8505C, revealing that papillary thyroid carcinoma cells are the most vulnerable. Crucially, a concentration of 65 µg/L, which is below current regulatory limits, triggered proliferative responses in all cell models.

DISCUSSION: These results suggest that Roundup® is a potent endocrine disruptor that exerts mutation-specific proliferative effects on thyroid cancer cells. Consistent growth stimulation at low, environmentally relevant doses suggests a potential tumor-promoting role, particularly in papillary carcinomas driven by the MAPK pathway. This evidence reinforces the need to revise risk assessments of GBHs (subcutaneous hypothyroidism) to take into account endocrine disruption and the potential for cancer progression beyond traditional toxicity.