Tanshinone IIA induces intrinsic apoptosis in osteosarcoma cells both in vivo and in vitro associated with
Sheng-Teng Huang1,2, Chao-Chun Huang3, Wen-Liang Huang1,2
1Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan.
Abstract:
Tanshinone IIA (Tan IIA), a phytochemical derived from the roots of Salvia miltiorrhiza, has been shown to inhibit growth and induce apoptosis in various cancer cells. The association of its inhibitory effect on the primary malignant bone tumor, osteosarcoma, with mitochondrial dysfunction remains unclear. This study aimed to investigate the anti-proliferative effects of Tan IIA on human osteosarcoma 143B cells both in vitro and in vivo. Administration of Tan IIA to NOD-SCID mice implanted with 143B cells led to significant inhibition of tumor development. The inhibition of proliferation, migration, and invasion was observed in 143B cells treated with Tan IIA. The tumor proliferation markers, Ki67 and PCNA, were suppressed and apoptosis by TUNEL assay was activated respectively. Apoptosis in the Tan IIA-treated 143B cells and xerograft mice was associated with the activation of caspase cascade via the modulation of Bcl-2 family. The CD31 was inhibited in Tan IIA-treated xenografts to indicate anti-neovasculization. Tan IIA administration resulted in a significant decrease in the mitochondrial fusion proteins, Mfn1/2 and Opa1, as well as an increase in the fission protein Drp1. We concluded that mitochondrial dysfunction associated with dynamic change was involved in apoptosis and anti-angiogenesis elicited by Tan IIA.
Insights
Tanshinone IIA inhibits osteosarcoma growth by inducing apoptosis and anti-angiogenesis. This phytochemical disrupts mitochondrial dynamics, offering a potential therapeutic strategy for this bone cancer.
Area of Science:
- Biochemistry
- Oncology
- Cell Biology
Background:
- Tanshinone IIA (Tan IIA), a Salvia miltiorrhiza-derived compound, exhibits anticancer properties.
- The mechanism of Tan IIA's effect on osteosarcoma, particularly concerning mitochondrial function, requires clarification.
Purpose of the Study:
- To investigate the anti-proliferative effects of Tan IIA on human osteosarcoma 143B cells.
- To elucidate the role of mitochondrial dysfunction in Tan IIA-induced apoptosis and anti-angiogenesis.
Main Methods:
- In vitro and in vivo studies using human osteosarcoma 143B cells and NOD-SCID mice xenografts.
- Analysis of cell proliferation, migration, invasion, apoptosis markers (TUNEL, caspase cascade, Bcl-2 family), proliferation markers (Ki67, PCNA), and angiogenesis marker (CD31).
- Assessment of mitochondrial dynamics by examining fusion (Mfn1/2, Opa1) and fission (Drp1) proteins.
Main Results:
- Tan IIA significantly inhibited osteosarcoma tumor development in vivo.
- In vitro, Tan IIA suppressed 143B cell proliferation, migration, and invasion.
- Tan IIA induced apoptosis via caspase activation and modulated Bcl-2 family proteins, suppressed proliferation markers, inhibited neovascularization (CD31), and altered mitochondrial dynamics by decreasing fusion proteins and increasing fission proteins.
Conclusions:
- Mitochondrial dysfunction, characterized by altered dynamics, plays a crucial role in Tan IIA-mediated apoptosis and anti-angiogenesis in osteosarcoma.
- Tan IIA demonstrates significant anti-proliferative and anti-angiogenic effects on osteosarcoma, suggesting its therapeutic potential.
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