Ameliorative Potential of Tamoxifen/Thymoquinone Combination in Patients with Breast Cancer: A Biochemical and Immunohistochemical Study

Abstract

Background: Breast cancer is one of the most common types of malignancies in females worldwide. Targeting the estrogen receptors alone with tamoxifen, reduces the incidence of estrogen receptor positive tumors but the possibility of development of tamoxifen resistance remains the most important adverse effect. Thymoquinone is an important constituent of the Nigella sativa plant (Black seed). It was found to be cytotoxic in several types of multidrug resistant human tumor cell lines. Objective: To detect the effects of the combination between tamoxifen and thymoquinone in patients with breast cancer. Methods: Eighty female patients with breast cancer were divided into four equal groups: control untreated group, tamoxifen treated group, thymoquinone treated group and tamoxifen + thymoquinone treated group. Tissue malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and transforming growth factor beta1 (TGF-β1) were determined in the tumor tissues. Parts of the tumor were subjected to immunohistochemical examination. The survival rate and the relapse rate were measured every year for five years. Results: Tamoxifen or thymoquinone alone or in combination induced significant increase in the 5-years survival rate, tumor CAT and SOD with significant decrease in the relapse rate, tumor tissue MDA, TNF-α, IL-6 and TGF-β1 and alleviated the immunohistochemical changes with significant increase in tissue caspase-3 expression and significant decrease in tissue bcl2 compared to the control untreated group. Conclusion: Tamoxifen/ thymoquinone combination had a better effect than each of these drugs alone on patients with breast cancer. So, the addition of thymoquinone to tamoxifen may represent a new therapeutic modality for management of breast cancer.