Synergistic cytotoxicity of tannic acid from Phyllanthus emblica and cisplatin in U2OS osteosarcoma cells: Surface ultramorphology and apoptotic gene modulation.

Tannic acid (TA) emerges as a promising anti-osteosarcoma agent. The application of TA in combination with cisplatin demonstrated promising synergistic activity with significant growth inhibitory and apoptotic effects. However, detailed surface ultramorphological alterations and the underlying mechanism of action are yet to be elucidated. Therefore, this study investigated the ultramorphological alterations and key mechanistic actions of TA and its combination with cisplatin against human osteosarcoma (U2OS) cells. The ultramorphological alteration of U2OS cells was evaluated using a scanning electron microscope (SEM). The mRNA expressions of key markers in mitogen-activated protein kinase (MAPK) and apoptotic pathways were evaluated using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Although surface ultramorphological alteration of U2OS cells was noted across all treatment groups, the combination treatment induced more prominent alteration. The cells appeared shrunk, with blebbed membranes and reduced appearance of lamellipodia and filopodia. Mechanistically, the combination of TA and cisplatin enhanced the former's anti-proliferative and apoptotic effects by upregulating the mRNA expression of ERK2, BAX, caspase-9, and caspase-3, and downregulating JNK1 and BCL-2. Therefore, the findings suggested that TA and its combination with cisplatin might exerted anti-proliferative and pro-apoptotic effects and induced surface ultrastructural changes in U2OS cells. These effects may be associated with ERK2, JNK1, and intrinsic apoptosis pathways, although further protein-level validation is required.