Background: The estimated cost of breast cancer (BCa) care in the U.S. is over 16 billion dollars yearly, more than any other cancer. Thus, identifying contributors to BCa development and barriers in BCa treatment is a continuing focus of BCa research. The per capita consumption of sugar in Americans has surged to 70 lb per year, and an increase in the consumption of added sugars is identified as a pivotal contributor to worldwide epidemics of non-communicable diseases including cancer. However, whether dietary sugar affects the efficacy of the chemotherapy in BCa is questionable. In current study, we investigated the impact of glucose or sucrose on the chemotherapeutic effect of chemo-agents, especially doxorubicin, in the growth of BCa cells or tumors.
Methods: BCa cell (human MDA-MB-231, SUM159, T47D, BT474, MDA-MB-468 and MCF-7) proliferation was assessed in 3-D culture system. BALB/C nu/nu mice were used to investigate tumor growth with/without doxorubicin treatment upon feeding sucrose enriched diet. Apoptotic gene array and microarray analysis were used to determine gene expression profile.
Results: Among six human BCa cells tested, glucose treatment (30 mM) promoted the growth of MDA-MB-231 and SUM159 cells after 10 days by 2.5 to 3 fold, respectively. In contrast, T47D, BT474, MDA-MB-468 and MCF-7 cells did not respond to glucose stimulation. Glucose treatment abrogated doxorubicin-induced cell apoptosis in triple negative BCa cells including MDA-MB-231 and SUM159 cells, and 4T1 (mouse) cells. Additionally, the apoptotic effect of chemotherapeutic agents, such as epirubicin, 5-FU and cyclophosphamide in MDA-MB-231 cells were also blocked by glucose treatment. Furthermore, gene expression analysis demonstrated that glucose significantly altered apoptotic genes in doxorubicin treated MDA-MB-231 cells. Compared to doxorubicin alone, glucose/doxorubicin co-treatment decreased a number of pro-apoptotic gene expression of including PEA15, BAX, and BcL2L11; while increased anti-apoptotic gene NFκB family. Finally, in mice bearing MDA-MB-231 cell derived tumors, doxorubicin (4 mg/kg body weight weekly for 4 weeks) inhibited the growth primary tumors by 50% compared to that in control mice. In the same study, for the mice fed with sucrose diet, treatment of doxorubicin only reduced the tumor growth by less than 20% compared to control diet fed mice without doxorubicin treatment, suggesting that dietary sugar might negatively impact the chemotherapeutic agent in BCa.
Conclusion: The results of our study indicated that glucose (sucrose) altered BCa responses to doxorubicin in vitro and in vivo. Therefore, dietary sugar may potentially interfere with the efficacy of chemotherapeutic agents in BCa patients which warrants further investigation. This study was support by a generous donation of Leighton and Lynda Steward, The William A. and Madeline Welder Smith Foundation and the University of Texas Startup Fund.
Citation Format: Yan Jiang, Patrea R. Rhea, Lorenzo Cohen, Peiying Yang. Modification of dietary sugar on the chemotherapeutic potential in breast cancer [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 232. doi:10.1158/1538-7445.AM2017-232