Inhibition of bone metastasis by fish oil, thymoquinone, and xanthone

Abstract

Breast cancer is the second most common form of cancer in the United States of America. If left untreated, breast cancer cells metastasize to the bone. At this stage, osteoclastogenesis is increased and bone loss is accelerated, causing fragile bones. Bone metastasis produces severe bone pain, and currently available medical treatment only focuses on reducing the pain and not on tumor growth or decreasing metastasis. Moreover, medications cause severe side effects, therefore, there is an increase in the use of alternative medicine and nutritional supplementation to decrease bone metastasis. The objectives of this research study, was to determine if fish oils (FO) with high docosahexaenoic acid content by itself or in combination with, thymoquinone (TQ) and xanthones (XN) would decrease bone metastasis in female mice. Four week old C57BL/6 athymic female mice were divided into the following groups: Group 1. Control (C); Group 2. Control Tumor (CT); Group 3. FO fed; Group 4. TQ fed; Group 5. XN fed; Group 6. FO+TQ; Group 7. FO+XN; and Group 8. TQ+XN. Athymic mice were fed their respective diets for 4 or 6 weeks and then groups 2 to 8 were injected with MDA‐MB‐231 breast cancer cells. Feeding their respective diets were continued for an additional 4 weeks. After four weeks, mice were euthanized, femurs and tibias were collected and scanned with a peripheral quantitative computed tomography (pQCT) densitometer.The scans of the right distal femur metaphysis (DFM) were analyzed and both FO and FO+TQ expressed the most significant and consistent bone protective properties, when compared to the CT group. The Total Bone Area (Tot B Ar) significantly decreased in the CT group (10%, p<0.05), when compared to that of the C group, but significantly increased in all the treatment groups. The total bone mineral content (Tot BMC) increased significantly in the FO+TQ treated group (6%, p<0.05). Trabecular bone mineral density (Tb BMD) increased in the FO (10%, p<0.05) and FO+TQ treated groups (14%, p<0.05), in comparison with the CT group. Although the other diets did attenuate bone metastasis in the DFM, they were to a lesser extent compared to the FO and FO+TQ groups.The proximal tibial metaphysis (PTM) showed increased Tot B Ar in the FO (24%, p<0.05), TQ (19%, p<0.05), FO+XN (24%, p<0.05) and TQ+XN (24%, p<0.05. The Trabecular Bone Area (Tb B Ar) also increased significantly in all the different treatments tested, compared to those of the CT mice. The Trabecular Bone Mineral Content (Tb BMC) was increased significantly after treated with FO (31%, p<0.05), TQ (53%, p<0.05) and TQ+XN (44%, p<0.05), when compared to those of the CT mice.In summary, FO protected the Tot B Ar and Tb BMD in the femur, while in the tibia, in addition to the Tot B Ar, it protected the Tb b Ar and Tb BMC. We conclude that FO protected femur and tibia from bone metastasis better than TQ and XN alone.Support or Funding InformationUniversity Research Initiative