Planta Med 2013; 79 - P86
DOI: 10.1055/s-0033-1336528

Modulation of Cancer-Related Signaling and Cytotoxicity by (Z)- and (E)- 3,3'4,5'-Tetramethoxystilbene Isolated from Eugenia rigida

MA Zaki 1, 2, P Balachandran 1, SI Khan 1, 3, M Wang 1, RM Abd slam 2, MH Hetta 2, D Pasco 1, 2, I Muhammad 1
  • 1National Center for Natural Products Research and
  • 3Department of Pharmacognosy, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677, USA
  • 2Department of Pharmacognosy, School of Pharmacy, Beni-Suef University, Beni-Suef, Egypt

Three stilbenes, (Z)- (1) and (E) (2)- 3,3'4,5'-tetramethoxystilbene, and (E)- 3,4',5-trimethoxystilbene (3), have been isolated from Eugenia rigida DC. Their structures were determined using NMR and HRESIMS. The less stable Z-stereoisomer (1), a new natural product, was prepared by E-Z photoisomerization of 2 under UV irradiation at 254nm, while 2,3,5,7-tetramethoxyphenanthrene (5) was generated at 365nm, which was identified by UPLC/MS and NMR. Compounds 1-3 were tested against a panel of luciferase reporter gene assays that assesses the activity of many cancer-related signaling pathways, where (Z)- isomer (1) was found to be more potent than (E)- isomer (2) at inhibiting the activation of Stat3, Smad2/3, myc, Ets, Notch and Wnt signaling with IC50 values between 40 – 80 µM. However, both compounds showed similar inhibition against Ap-1 and NF-κB signaling. In addition, the Z- isomer (1) demonstrated cytotoxic activity towards human leukemia (HL-60) cells, as well as solid tumor cells of epidermal, breast and ovarian carcinoma, and skin melanoma with IC50 values between 5.3 – 16.6 µM, while the E-isomer (2) was inactive up to 35 µM. Interestingly, 2 showed antioxidant activity by inhibition of ROS generation to 50% at 33.3 µM in PMA-induced HL-60 cells, while 1 did not exhibit any effect.

Acknowledgements. The authors sincerely thank Dr. Vijayasankar Raman, Dr. Bharathi Avula, Mr. Frank Wiggers and Mr. John Trott, NCNPR, for providing information on plant, recording mass spectra, running NMR spectra and cytotoxitciy assay, respectively. This work is supported in part by a contract from the University of Mississippi Medical Center Cancer Institute and the USDA Agricultural Research Service Specific Cooperative Agreement No. 58 – 6408 – 02 – 1-612. One of us (MA Zaki) is thankful to Egyptian Govt. for scholarship.