Lignan-rich sesame seed negates the tumor-inhibitory effect of tamoxifen but maintains bone health in a postmenopausal athymic mouse model with estrogen-responsive breast tumors

Abstract

Flaxseed, the richest source of mammalian lignan precursors, enhances the tumor growth-inhibitory effect of tamoxifen while exerting no adverse effects on other estrogen-responsive tissues such as bone. Ingestion of sesame seed produces mammalian lignans comparable with flaxseed, but its anticancer potential is unknown. This study determined the interactive effects of sesame seed and tamoxifen on established MCF-7 tumor growth and bone health in ovariectomized athymic mice simulating a postmenopausal condition. Mice with established MCF-7 tumors were treated for 8 weeks with (1) basal diet (negative control), (2) 10% sesame seed, (3) basal diet + tamoxifen implant, (4) 10% sesame seed + tamoxifen implant, or (5) basal diet + estrogen implant (positive control). Weekly palpable tumor size, final tumor weight, cell proliferation, and apoptosis were measured. Bone mineral content, bone mineral density, and biomechanical strength testing were performed on the femur and lumbar vertebrae. Sesame seed induced regression of established tumor size similar to the negative control but tended to negate the tumor-inhibitory effect of tamoxifen, in part by reducing apoptosis. Sesame seed combined with tamoxifen induced higher bone mineral content, bone mineral density, and biomechanical strength in the femur and lumbar vertebrae than either treatment alone. A significant positive relationship was found between final tumor weight and bone strength parameters. Sesame seed is not protective and negatively interferes with tamoxifen in inducing regression of established MCF-7 tumor size but beneficially interacts with tamoxifen on bone in ovariectomized athymic mice.