# Theaflavin-3,3′-digallate triggers apoptosis in osteosarcoma cells via the caspase pathway

## TL;DR

Theaflavin-3,3′-digallate reduces osteosarcoma cell viability and induces apoptosis through the caspase pathway in both lab and animal models.

## Contribution

This study demonstrates that TF3 induces apoptosis in osteosarcoma cells via the caspase pathway, supported by in vivo evidence.

## Key findings

- TF3 significantly reduced viability of 143B and U2OS osteosarcoma cells.
- TF3 upregulated cleaved caspase-3 and -9, and increased levels of apoptosis-related proteins like Bax and cytochrome c.
- In a xenograft model, TF3 significantly reduced tumor volume in osteosarcoma.

## Abstract

Osteosarcoma is a cancer associated with a guarded prognosis. Various compounds can induce apoptosis in osteosarcoma cells. Theaflavin-3,3′-digallate (TF3) has been demonstrated to alter cell growth and induce apoptosis in various cancer cells. The present study investigated the apoptotic effect of TF3 on osteosarcoma cells. It further explored key apoptotic pathways activated by TF3. Viability of 143B and U2OS osteosarcoma cells after TF3 treatment was assessed. The effects of TF3 on key apoptotic pathways were analyzed. Furthermore, a xenograft mouse model of osteosarcoma was established for in vivo experiments. The results indicated that TF3 significantly reduced the viability of 143B and U2OS cells. Western blotting revealed that TF3 upregulated the expression of cleaved caspase-3 and cleaved caspase-9 in osteosarcoma cells. In addition, TF3 increased the levels of phosphorylated histone H2Ax, Bax, Bak1, and cytochrome c, while reducing the levels of Mcl-1 and survivin in osteosarcoma cells. Furthermore, TF3 significantly reduced the average tumor volume in the xenograft model. Overall, this study suggests that TF3 induces apoptosis in osteosarcoma cells, primarily by regulating the caspase pathway.