BackgroundCordycepin, the main active ingredient of a traditional Chinese herbal remedy – extracted from Cordyceps sinensis – has been demonstrated as a very effective anti-inflammatory and antitumor drug. The present study investigated its antitumor effect on pancreatic cancer, a highly aggressive cancer with extremely poor prognosis due to malignancy, and clarified its underlying mechanism both in vitro and in vivo.MethodsThe antitumor viability of cordycepin on human pancreatic cancer MIAPaCa-2 and Capan-1 cells was determined by colony formation assays. Annexin V/PI double staining and flow cytometry assay were used to investigate whether cordycepin induced apoptosis and cell cycle arrest. The mitochondrial membrane potential (ΔΨm) was analyzed by Rhodamine 123 staining, and expression of related proteins evaluated by Western blot and immunohistochemistry, both on pancreatic cancer cells and tumor xenografts to reveal the potential mechanism for the effect of cordycepin. Furthermore, the in vivo efficacy was examined on nude mice bearing MIAPaCa-2 cell tumors treated by intraperitoneal injection of cordycepin (0, 15, and 50 mg/kg/d) for 28 days.ResultsCordycepin inhibited cell viability, proliferation and colony formation ability and induced cell cycle arrest and early apoptosis of human pancreatic cancer cells (MIAPaCa-2 and Capan-1) in a dose- and time-dependent manner. The same effect was also observed in vivo. Decrease of ΔΨm and upregulation of Bax, cleaved caspase-3, cleaved caspase-9, and cleaved PARP as well as downregulation of Bcl-2 both in vitro and in vivo indicated that the mitochondria-mediated intrinsic pathway was involved in cordycepin’s antitumor effect.ConclusionOur data showed that cordycepin inhibited the activity of pancreatic cancer both in vitro and in vivo by regulating apoptosis-related protein expression through the mitochondrial pathway and suggest that cordycepin may be a promising therapeutic option for pancreatic cancer.

Osthole is an antitumor compound, which effect on Gallbladder cancer (GBC) has been not elucidated. This study focused on its anti-GBC effect and mechanism both in vitro and in vivo. The antiproliferation effect on cell lines NOZ and SGC-996 were measured by cell counting kit-8 (CCK-8) and colony formation assay. The effects on cell apoptosis and cell cycle were investigated by flow cytometry assay. The migration effect was checked by transwell assay and the expressions of proteins were examined by Western Blots. Also, we did an in-vivo experiment by intraperitoneal injection of osthole in nude mice. The results showed that cell proliferation and viability were inhibited in a dose- and time-dependent manner. The similar phenomenon was also found in vivo. Flow cytometric assay confirmed that osthole inhibited cells proliferation via inducing apoptosis and G2/M arrest. Transwell assay indicated that osthole inhibited the migration in a dose-dependent manner. Expression of key proteins related with apoptosis and cell cycle were testified after osthole treatment. Also, we found the key proteins involved in the JAK/STAT3 signal way decreased after osthole treatment. This study suggested that osthole can inhibit the progression of human GBC cell lines, thus maybe a potential drug for GBC treatment.

Napabucasin (also known as BBI608) is a natural naphthoquinone originally identified as a cancer cell stemness inhibitor. Accumulated in vitro and in vivo evidence demonstrated that napabucasin showed significant anticancer effects in various types of cancers. Napabucasin inhibits cancer cell proliferation, induces apoptosis and cell cycle arrest, and suppresses metastasis and relapse. Such anticancer activities of napabucasin mainly rely on the inhibition of cancer stemness by targeting signal transducer and activator of transcription 3 (STAT3) and its related gene inhibition. However, several novel molecular targets for napabucasin, such as NAD(P)H:quinone oxidoreductase 1 (NQO1) and thioredoxin reductase 1 (TrxR1), have been reported. Napabucasin represents a promising anticancer lead for multiple cancers. In this mini review, the anticancer potential and the molecular mechanism of napabucasin will be briefly highlighted.

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