+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Targeting EP4 downstream c-Jun through ERK1/2-mediated reduction of DNMT1 reveals novel mechanism of solamargine-inhibited growth of lung cancer cells

, : Targeting EP4 downstream c-Jun through ERK1/2-mediated reduction of DNMT1 reveals novel mechanism of solamargine-inhibited growth of lung cancer cells. Journal of Cellular and Molecular Medicine (): -

NlmCategory="UNASSIGNED">Lung cancer is the most common cancer and the leading cause of cancer deaths worldwide. We previously showed that solamargine, one natural phytochemicals from traditional plants, inhibited the growth of lung cancer cells through inhibition of prostaglandin E2 (PGE2 ) receptor EP4. However, the potential downstream effectors of EP4 involving in the anti-lung cancer effects of solamargine still remained to be determined. In this study, we further verified that solamargine inhibited growth of non-small-cell lung cancer (NSCLC) cells in multiple cell lines. Mechanistically, solamargine increased phosphorylation of ERK1/2. Moreover, solamargine inhibited the protein expression of DNA methyltransferase 1 (DNMT1) and c-Jun, which were abrogated in cells treated with MEK/ERK1/2 inhibitor (PD98059) and transfected with exogenously expressed DNMT1 gene, respectively. Interestingly, overexpressed DNMT1 gene antagonized the effect of solamargine on c-Jun protein expression. Intriguingly, overexpressed c-Jun blocked solamargine-inhibited lung cancer cell growth, and feedback resisted the solamargine-induced phosphorylation of ERK1/2. A nude mouse xenograft model implanted with lung cancer cells in vivo confirmed the results in vitro. Collectively, our results show that solamargine inhibits the growth of human lung cancer cells through reduction of EP4 protein expression, followed by increasing ERK1/2 phosphorylation. This results in decrease in DNMT1 and c-Jun protein expressions. The inter-correlations between EP4, DNMT1 and c-Jun and feedback regulation of ERK1/2 by c-Jun contribute to the overall responses of solamargine in this process. This study uncovers an additional novel mechanism by which solamargine inhibits growth of human lung cancer cells.


PMID: 27620163

DOI: 10.1111/jcmm.12958

Other references

Veenenbos, J.A.J., 1955: Result of the cereal rust inquiries 1952-54. Cereal rusts (Puccinia spp.) assumed a severe form in Holland in 1952, but in 1953 and 1954 the outbreaks were of only moderate intensity. Rye was attacked by P. dispersa in all three years and by P. graminis in the first two, the latter, however,...

Raaijmakers, Leon, 2004: A new site of Clavulinopsis vernalis in the Netherlands. A new find of Clavulinopsis vernalis is reported, the second one since 1947, and an overview is given of all the sites and years where it has been found previously.

Anonymous, 2004: Associate veterinarians: Hiring and retention remain difficult challenge. DVM 35(7): 3F

Navrátil, K., 1966: Hexadecyl Spofa. (Aerosol). Ceskoslovenska Farmacie 15(8): 446-446

Brandberg, O., 1945: Sulfanilamide drugs and acute nephritis. Acta Paediatrica 32(3-4): 336-343

Ishizaki H.; Kohno M.; Tsuchida M.; Umino M.; Hazumi Y.; Katoh S.; Kunoh H., 1983: Yearly fluctuations in the occurrence of thiophanate methyl resistant strains of the pear scab fungus in pear orchards at karasu town mie prefecture japan. Distribution of thiophanate-methyl-resistant strains of Venturia nashicola Tanaka et Yamamoto was surveyed in 1976-1980 at the Kawahara area, Karasu Town, Mie Prefecture, where Japanese pear was severely damaged by the occurrence of thiophanate-me...

Preston, C.D.; Stewart, N.F., 1994: Irish pondweeds V potamogeton x Suecicus K Richter in Co Donegal, new to Ireland. Irish Naturalists' Journal 24(12): 485-489

Case, D.C.Jr; Ervin, T.J.; Boyd, M.A., 1996: Routine bone marrows are necessary in acute myelogenous leukemia. Blood 88(10 SUPPL 1 PART 1-2): 82A

Raviña-Eirín, E.; Sánchez-Rodríguez, B.; Gómez-Amoza, J.Luis.; Martínez-Pacheco, Rón., 2015: Evaluation of the hyperbranched polymer Hybrane H1500 for production of matricial controlled-release particles by hot-melt extrusion. Extrudates of the hyperbranched polymer Hybrane H1500 prepared by hot melt extrusion, with five particle sizes (from <250 μm to 1.5-2.0 mm) and three drug content (10, 20 and 30%) of acetaminophen or caffeine, were evaluated in this study as p...

Hua, S.; Jouve, S., 2004: A primitive marine gavialoid from the paleocene of Morocco. The discovery of a new genus and species of gavialoid at the Danian-Thanetian boundary, in the Oulad Abdoun Basin of Morocco, is consistent with an African origin of Gavialoidea. Argochampsa krebsi, n.g. n.sp., exhibits a particular shape of the a...