Abstract
Increasing evidence suggests that traditional Chinese medicine strategies are obviously beneficial for cancer treatment, but scientific research on the underlying molecular mechanisms is lacking. We report that ursolic acid, a bioactive ingredient isolated from Radix Actinidiae chinensis, has strong antitumour effects on osteosarcoma cells. Functional studies showed that ursolic acid inhibited tumour cell proliferation and promoted the apoptosis of a variety of osteosarcoma cells. Ursolic acid had a synergistic cytotoxic effect with cisplatin on osteosarcoma cells. In a mouse osteosarcoma xenograft model, low-dose cisplatin combined with ursolic acid significantly reduced tumour growth. Notably, ursolic acid reversed weight loss in mice treated with cisplatin. Mechanistic studies showed that ursolic acid degraded ferritin by activating autophagy and induced intracellular overload of ferrous ions, leading to ferroptosis. In addition, ursolic acid enhanced the DNA-damaging effect of cisplatin on osteosarcoma cells. Taken together, these findings suggest that ursolic acid is a nontoxic adjuvant that may enhance the effectiveness of chemotherapy in osteosarcoma.
Highlights
Osteosarcoma (OS) is a type of sarcoma that originates from osteoblast mesenchymal cells and is most commonly seen in children and adolescents aged 15-19 years [1]
The results showed that 35 μM Ursolic acid (UA) combined with 20 μM Cis had the most obvious effect on the proliferation of OS cells (Figure 1(a))
The results showed that the apoptosis rate of OS cells was the highest in the UA+Cis group and was higher in the UA+Cis group than that in the Cis or UA alone group but that the apoptosis rate in all three groups was significantly higher than that in the control group (Figure 1(d))
Summary
Osteosarcoma (OS) is a type of sarcoma that originates from osteoblast mesenchymal cells and is most commonly seen in children and adolescents aged 15-19 years [1]. Current treatment strategies, including chemotherapy combined with aggressive surgical resection, have significantly improved the survival of patients with OS [2]. The recurrence rate is still 30-40%, and the 10-year survival rate is 20-30% due to pulmonary metastasis [3]. Chemotherapy, such as cisplatin (Cis), is the most effective treatment for cancer and OS [4,5,6]. There is an urgent need to investigate alternative anticancer approaches, such as the use of food and herbal supplements in combination with current chemotherapy to improve the therapeutic effectiveness of existing drugs. The development of effective, nontoxic therapeutic strategies, i.e., the application of natural active substances with proven anticancer effects, may be a more promising approach for the prevention and treatment of OS
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