Breast cancer is the most common cancer and the second leading cause of cancer death in American women. Rho GTPases play a crucial role in regulating different cellular functions, including cell proliferation, gene expression, cell morphology, actin polymerization, cell motility, metastasis and apoptosis. Wiskott-Aldrich syndrome protein family verprolin-homologous protein2 (WAVE2) is a member within the Wiskott-Aldrich syndrome protein (WASP) family displays a significant role in actin polymerization and cytoskeletal organization which, are essential for cellular migration and invasion. γ-Tocotrienol is a natural isoform within the vitamin E family that displays anticancer activity against a variety of cancer cell types. Pterostilbene is a natural dimethyl ether analog of resveratrol that has several beneficial effects such as anticancer activity. Studies were conducted to examine the effects of combined γ-tocotrienol and pterostilbene on Rac1/WAVE 2 signaling in mouse +SA and human MDA-MB231 breast cancer cells and cellular migration. Results show that combined treatment of γ-tocotrienol and pterostilbene caused a synergistic inhibition of both mouse +SA and human MDA-MB231 breast cancer cells growth, and corresponding reduction in Rac1/WAVE2 signaling as characterized by a significant inhibition in the levels of phospho-Rac1/cdc42, WAVE2, Arp2, and Arp3 expression. Additional studies indicated that this combination resulted in a significant inhibition in mammary cancer cell migration. In summary, these findings strongly suggest that combined treatment of γ-tocotrienol with pterostilbene may provide great benefit as a therapeutic approach in the treatment of metastatic breast cancer. Supported by a grant from the Louisiana Cancer Foundation.

Citation Format: Ibrahim G. Algayadh, Paul William Sylvester. Synergistic anticancer effects of combined γ-tocotrienol and pterostilbene is associated with a suppression in Rac1/WAVE 2 signaling in highly malignant breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1053. doi:10.1158/1538-7445.AM2017-1053