Triptolide-induced in vitro and in vivo cytotoxicity in human breast cancer stem cells and primary breast cancer cells

Abstract

We investigated the potential efficacy of the Chinese herbal extract triptolide for the treatment of human breast cancer by measuring the triptolide-induced cytotoxicity in cultures of human primary breast cancer cells (BCCs) and breast cancer stem cells (BCSCs) in vitro and in vivo. Human BCCs and BCSCs from invasive ductal carcinoma samples were cultured and treated with 0.1, 0.5 or 1.0 µM triptolide. Cell death and apoptosis were measured after 24, 48 and 72 h of treatment. Mammospheres were found to be highly tumorigenic when implanted subcutaneously in nude BALB/c mice. Triptolide was cytotoxic against both human primary BCCs and BCSCs in vitro (P<0.05), but the cytotoxicity was stronger against the BCCs. In response to 1 µM triptolide for 72 h, the apoptotic rates were approximately 60% for BCCs and 30% for BCSCs. The BCSCs exhibited a high formation rate of tumors when implanted subcutaneously in nude BALB/c mice. Triptolide treatment in vivo significantly inhibited tumor growth compared with mock treatment. In conclusion, the cytotoxicity of triptolide against BCCs and BCSCs in vitro and in vivo suggests that this natural diterpenoid triepoxide compound may have clinical applications for the suppression of breast tumor growth.

Synergistic Antitumor Effect of Triptolide and Cisplatin in Cisplatin Resistant Human Bladder Cancer Cells

“…11,12 TPL significantly enhanced cytotoxicity in breast stem cells and primary cancer cells. 11 In malignant glioma cells TPL inhibited cell proliferation by inducing cell cycle arrest and significantly suppressed migratory and invasive properties. 12 We investigated whether TPL would synergistically potentiate the antitumor effect of cisplatin in a cisplatin resistant human bladder cancer cell line.…”

Triptolide inhibits TGF-β1-induced cell proliferation in rat airway smooth muscle cells by suppressing Smad signaling

“…Triptolide has been shown to be safe and clinically beneficial in several autoimmune diseases, such as rheumatoid arthritis and asthma. Besides, triptolide has been reported to inhibits proliferation and induce apoptosis of cancer cells in vitro and reduce the growth and metastases of tumors in vivo [13][14][15][16][17]. Triptolide or its derivative has also been shown to be effective in the treatment of lung inflammation and fibrosis in animal models [18][19][20].…”

Targeting cancer stem cells and signaling pathways by phytochemicals: Novel approach for breast cancer therapy

“…Triptolide exerted potent cytotoxic activity and induced apoptosis in both breast cancer cells as well as breast CSCs. Triptolide also inhibited tumor growth in nude BALB/c mice injected with breast CSCs [189]. Ganglioside GD2 has been recently discovered as a novel breast CSC marker, and the enzyme GD3 synthase (GD3S) is critically involved in the synthesis of GD2.…”