Poster Topical Area: Dietary Bioactive Components

Location: Hall D

Poster Board Number: 352

P08-094 - Combinatorial Effect of Tocotrienols and Topoisomerase II Inhibitors on Breast Cancer cells

Monday, Jun 11
8:00 AM – 3:00 PM

Background: Etoposide, a Mayapple podophyllotoxin derivative, is a semisynthetic compound found to be effective against a broad spectrum of cancer types such as carcinoma of lungs, bladder, breast, gastric, testicular, acute myelocytic leukemia, and lymphoma. [1] Despite its potent antitumor activity, as a topoisomerase II poison, Etoposide is constrained by its low aqueous solubility and its clinical use is limited because of its adverse effects, mainly myelosuppression and the development of secondary leukemia. [2, 3]. Trying to combine health and diet, and reducing Etoposide toxicity, we aimed in this project to study the mode of action of Etoposide along with the potent antioxidant Vitamin E member, Gamma tocotrienol (γ-TCT) reported to be a promising anticancer agent [4], on survival and apoptosis pathways in breast cancer cell line MDA-MB-231, and to investigate the potential synergistic effect of Gamma tocotrienol on Etoposide.Materials and
MDA-MB-231 cells were incubated with different Etoposide and γ- TCT concentrations for 48 hours, separately and in combination. Cell proliferation was determined using WST-1 (Roche) reagent. Apoptosis was assessed by Cell death ELISA and annexinV/propidium iodide staining, and the cell cycle analysis was performed in addition to propidium iodide staining.
As reported, Etoposide and γ- TCT exhibited antiproliferative effects on MDA-MB-231 cells when applied separately. In combination, the reduction in proliferation was extremely significant with a noticeable increase in DNA fragmentation leading apoptosis. Moreover, the combination induced a major S-phase arrest.
These fndings suggest that γ-TCT may be a useful chemotherapeutic adjuvant to potentiate the pharmacological action of etoposide and ameliorate its adverse effects.

Funding Source: SRDC, Lebanese American University, Beirut Lebanon

CoAuthors: Maya Idriss – Beirut Arab University; Mohamed Moustafa – BAU; Rajaa Fakhoury – BAU

Sandra Rizk

Lebanese American University
Beirut, Beyrouth, Lebanon