Abstract
Triptolide, extracted from the herb Tripteryglum wilfordii Hook.f that has long been used as a natural medicine in China, has attracted much interest for its anti-cancer effects against some kinds of tumours in recent years. Artesunate, extracted from the Chinese herb Artemisia annua, has proven to be effective and safe as an anti-malarial drug that possesses anticancer potential. The present study attempted to clarify if triptolide enhances artesunate-induced cytotoxicity in pancreatic cancer cell lines in vitro and in vivo. In vitro, to test synergic actions, cell viability and apoptosis were analyzed after treatment of pancreatic cancer cell lines with the two agents singly or in combination. The molecular mechanisms of apoptotic effects were also explored using qRT-PCR and Western blotting. In vivo, a tumor xenograft model was established in nude mice, for assessment of inhibitory effects of triptolide and artesunate. We could show that the combination of triptolide and artesunate could inhibit pancreatic cancer cell line growth, and induce apoptosis, accompanied by expression of HSP 20 and HSP 27, indicating important roles in the synergic effects. Moreover, tumor growth was decreased with triptolide and artesunate synergy. Our result indicated that triptolide and artesunate in combination at low concentrations can exert synergistic anti-tumor effects in pancreatic cancer cells with potential clinical applications.
Highlights
Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in pancreas, one of the highest fatality rates of all cancers, extremely poor prognosis and resistant to current chemotherapies, new strategies or reagents to tackle this disease are needed.Triptolide (TPL) is a diterpenoid triepoxide and the principal active ingredient of Tripterygium wilfordii Hook. f. that has been used as a natural medicine in China for hundreds of years, which has pharmacological and biochemical properties in the treatment of autoimmune diseases such as nephritis and rheumatoid arthritis for centuries (Wang et al, 2012; Huang et al, 2013; Hung et al, 2013)
Our result indicated that triptolide and artesunate in combination at low concentrations can exert synergistic anti-tumor effects in pancreatic cancer cells with potential clinical applications
Artesunate (ART), is a derivative of artemisinin isolated from the traditional Chinese herb Artemisia annua L, has been approved by the Chinese government for the treatment of malaria, especially against cerebral malaria, more recently, scholars had found it has a wide range of biological activities, such as hepatoprotective, antioxidative, anti-inflammatory, antidiabetic, antiallergic, and antibacterial effects (Ma et al, 2011; Jiang et al, 2012; Mao et al, 2012; Zhou et al, 2012)
Summary
Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in pancreas, one of the highest fatality rates of all cancers, extremely poor prognosis and resistant to current chemotherapies, new strategies or reagents to tackle this disease are needed. Triptolide is able to potently inhibit the growth of human cancer cells in vitro and prevents tumor growth in vivo via inhibiting cell proliferation and inducing apoptosis (Li et al, 2012; Tao et al, 2012; Chueh et al, 2013). Triptolide possess both immunosuppressive and antifertility activities through its ability to inhibit the proliferation of both activated monocytes and spermatocytes (Huang et al, 2012; Xiaowen et al, 2012; Zhang et al, 2012). The present study was designed to determine combined efficacy of triptolide and artesunate on pancreatic cancer cell lines in vitro and in vivo
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