Modifications in work-life balance have contributed to higher rates of cervical cancer in younger adults. Ginsenoside Rk1, a low-abundance saponin component of ginseng, is recognized for its capacity to restrain growth and survival across multiple human cancer cell types. Nonetheless, its influence on the proliferative capacity of HeLa cells has not been established. Exposure to ginsenoside Rk1 caused HeLa cells to arrest in the G0/G1 phase in a manner dependent on concentration, while also suppressing subsequent cell division and expansion. The agent robustly engaged the apoptotic machinery, involving key mediators such as caspase 3, PARP, and caspase 6. It further upregulated LC3B protein abundance, pointing to enhanced autophagic activity. Integrated Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses identified pronounced downregulation of the protein processing in the endoplasmic reticulum pathway. These patterns were confirmed through real-time quantitative PCR and western blot analyses, which documented sharp reductions in the levels of YOD1, HSPA4L, DNAJC3, and HSP90AA1 transcripts and proteins in treated cells. YOD1 displayed the most substantial decline in response to ginsenoside Rk1. The observed cytotoxicity of ginsenoside Rk1 toward HeLa cells can be attributed to interference with endoplasmic reticulum-based protein maturation combined with amplified apoptotic signaling. These mechanisms highlight YOD1 as a candidate target for future cervical cancer interventions.
