| First Author | Kumar R | Year | 2012 |
| Journal | Carcinogenesis | Volume | 33 |
| Issue | 10 | Pages | 1909-18 |
| PubMed ID | 22767649 | Mgi Jnum | J:192955 |
| Mgi Id | MGI:5466847 | Doi | 10.1093/carcin/bgs219 |
| Citation | Kumar R, et al. (2012) Nexrutine(R) inhibits tumorigenesis in mouse skin and induces apoptotic cell death in human squamous carcinoma A431 and human melanoma A375 cells. Carcinogenesis 33(10):1909-18 |
| abstractText | Nexrutine((R)) (NX), a herbal extract from Phellodendron amurense, has been shown to possess antitumor, antimicrobial, anti-inflammatory and other biological activities. In the present investigation, we explored the mechanism of chemopreventive/chemotherapeutic efficacy of NX against skin cancer. Single application of NX (1.0mg/mouse) prior to 12-O-tetradecanoylphorbol 13-acetate (TPA) application significantly inhibited TPA-induced skin edema, hyperplasia, thymidine incorporation and ornithine decarboxylase (ODC) activity; expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS); phosphorylation of extracellular signal-regulated kinases (ERK) 1/2, p38 and c-jun N-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs); and activation of I kappa B kinase (IKK), IkappaBalpha and nuclear factor-kappa B (NF-kappaB) in mouse skin. In a two-stage mouse skin tumorigenesis model, it was found that twice-weekly treatment of NX prior to TPA application in 7,12-dimethylbenz[alpha]anthracene (DMBA)-initiated animals showed reduced tumor incidence, lower tumor body burden and significant delay in latency period compared with DMBA-initiated and TPA-promoted animals. Furthermore, the therapeutic efficacy of NX was assessed against human squamous carcinoma (A431) and human melanoma (A375) cells. A431 and A375 cells treated with NX (2.5-10.0 mug/ml, 48h) showed a decrease in viability and enhanced cell cycle arrest at the G(0)/G(1) phase and apoptosis; however, NX had minimal cytotoxic effect on HaCaT cells and primary murine keratinocytes, suggesting its high therapeutic index. In addition, NX treatment also modulates the levels of Bax and Bcl-2 proteins along with cytochrome c release, cleavage and enhanced expression of poly (adenosine diphosphate-ribose) polymerase as well as catalytic activities of caspases 3 and 9 in both A431 and A375 cells. Based on our in vivo and in vitro studies, NX could be useful in the management (chemoprevention as well as chemotherapy) of skin cancer. |
