Anti-cancer and Sensibilisation Effect of Triptolide on Human Epithelial Ovarian Cancer

Abstract

Introduction: Advanced ovarian cancer is the main cause of ovarian cancer deaths, and it is important to seek safe and effective phytochemicals to suppress cancer or lower the chemotherapy resistance of ovarian cancer.Methods: This study evaluated the effect of Triptolide (TPL) on the proliferation, cycle distribution, apoptosis, and ultra-structure of COC1/DDP cells in vitro, as well as the anti-cancer effect and sensibilisation effect of TPL in vivo.Results: The results indicated that TPL could significantly inhibit the growth of COC1/DDP cells (P<0.05), and 3 ng/ml TPL and 50 ng/ml TPL made COC1/DDP cells present obvious apoptosis characteristics and arrest 35% and 55% of COC/DDP cells in the G0/G1 phase, respectively (P<0.05). The animal experiments also indicated that 0.1mg/kg.d TPL significantly reduced the tumour weight and the spleen cell transformation rate (SI), and it lowered the inflammatory factors IL-2 and TNF-a in rat serum (P<0.05). Moreover, the significant reduction of p-Akt and p-GSK3β made the TPL+DDP possess the highest apoptosis rate [(51.13±3.325)%] in COC1/DDP cells.Conclusions: TPL used in combination with DDP may produce a synergistic anti-cancer effect that warrants further investigation for its potential clinical applications in the treatment of epithelial ovarian cancer.

Discovery of potential targets of Triptolide through inverse docking in ovarian cancer cells

“…TPL, a pure compound extract from the Chinese traditional medicine T. wilfordii, has significant cytotoxic effects on ovarian cancer (Hu et al, 2016). However, the mechanisms of TPL on ovarian cancer and its target genes have not been studied (Westfall, Nilsson & Skinner, 2008).…”

“…One hypothesis that TPL covalently modifies proteins via epoxide ring-opening reactions has been proved that how TPL stimulates apoptosis of cancer cells (Hu et al, 2016). Even though the target proteins are undefined, it is evident that TPL has some kind of explained effects on the anticancer.…”

Geraniin suppresses ovarian cancer growth through inhibition of NF-κB activation and downregulation of Mcl-1 expression

“…Many natural compounds such as flavones, flavonoids, and antioxidants have exhibited toxicity against ovarian cancer cells . It has been reported that triptolide, a diterpene triepoxide, exerts growth‐suppressive effects on human epithelial ovarian cancer cells . Curcumin, a polyphenolic compound found in turmeric, can trigger apoptotic death in ovarian cancer cells by disrupting calcium homeostasis .…”

Inhibition effect of triptolide on human epithelial ovarian cancer via adjusting cellular immunity and angiogenesis

“…Numerous studies indicate that the mechanism of tumor occurrence, development, invasion, metastasis and resistance is complex (4)(5)(6)(7)(8)(9). As one of the most well-known natural products, triptolide (TPL) had been used as an anti-inflammatory agent for rheumatoid arthritis for a long time in China, and was also recognized as a potential medicine for various types of cancers (10)(11)(12)(13)(14)(15)(16) although some researchers showed its potential toxicity on animal liver, kidney, testes, ovary and heart (17).…”

“…As one of the most well-known natural products, triptolide (TPL) had been used as an anti-inflammatory agent for rheumatoid arthritis for a long time in China, and was also recognized as a potential medicine for various types of cancers (10)(11)(12)(13)(14)(15)(16) although some researchers showed its potential toxicity on animal liver, kidney, testes, ovary and heart (17). Recent studies indicated that TPL induced cell apoptosis by inhibiting nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) in a p53-independent pathway, producing reactive oxygen species (ROS) and inactivating the PI3K/Akt signal pathway (9,16,(18)(19)(20)(21). In previous studies, our group proved that the TPL effectively inhibited cell growth, proliferation, metabolism, survival and cancer genesis by regulating the PI3K/Akt pathway (22).…”