Switch to low-fat diet improves outcome of acute lymphoblastic leukemia in obese mice
Abstract Background It is becoming increasingly recognized that weight and nutritional status can impact cancer survival. We have previously shown that obese mice with syngeneic acute lymphoblastic leukemia (ALL) have poorer response to chemotherapy treatment than control mice. We therefore investig...
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| Format: | Article |
| Language: | English |
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BMC
2018-11-01
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| Series: | Cancer & Metabolism |
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| Online Access: | http://link.springer.com/article/10.1186/s40170-018-0189-0 |
| _version_ | 1818448735962660864 |
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| author | Jonathan Tucci Waseem Alhushki Ting Chen Xia Sheng Yong-Mi Kim Steven D. Mittelman |
| author_facet | Jonathan Tucci Waseem Alhushki Ting Chen Xia Sheng Yong-Mi Kim Steven D. Mittelman |
| author_sort | Jonathan Tucci |
| collection | DOAJ |
| description | Abstract Background It is becoming increasingly recognized that weight and nutritional status can impact cancer survival. We have previously shown that obese mice with syngeneic acute lymphoblastic leukemia (ALL) have poorer response to chemotherapy treatment than control mice. We therefore investigated whether dietary intervention could improve outcome from the most common pediatric cancer, ALL. Methods Diet-induced obese (DIO) mice raised on a 60% calories from fat diet and control mice were implanted with syngeneic ALL cells. Some DIO mice were switched to the low-fat control diet. Survival from ALL was assessed without or with chemotherapy treatment starting at the time of the diet switch. Cells from DIO mice before and after diet switch were assessed by FACS for BrdU incorporation and phosphorylation status of AKT, S6K, and EIF2a. Similar experiments were done with human ALL xenografts. Mouse and human ALL cells were cultured in media with 10% or 5% fetal bovine serum, and sensitivity to chemotherapies assessed. Results DIO mice had poorer survival (17%) after vincristine monotherapy than control mice on a 10% low fat diet (42%; n = 12/group; p = 0.09, log rank). However, switching obese mice to the low-fat diet prior to initiation of vincristine led to dramatically improved survival (92%, p < 0.01 vs both other groups). In vitro, FBS restriction made murine and human ALL cells more sensitive to vincristine. Interestingly, while serum restriction enhanced ALL sensitivity to dexamethasone and l-asparaginase, dietary switch did not improve survival of DIO mice treated with either drug in monotherapy. Thus, it appears that dietary intervention has a unique effect to improve ALL cell sensitivity to vincristine in vivo. Conclusions We report herein that a dietary intervention can improve ALL outcome in a preclinical model. Further work is needed to identify the mechanisms of this effect and investigate potential impact on human leukemia in patients. |
| first_indexed | 2024-12-14T20:24:15Z |
| format | Article |
| id | doaj.art-e26c2432f7604924b6e1d9475d9cfe5f |
| institution | Directory Open Access Journal |
| issn | 2049-3002 |
| language | English |
| last_indexed | 2024-12-14T20:24:15Z |
| publishDate | 2018-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer & Metabolism |
| spelling | doaj.art-e26c2432f7604924b6e1d9475d9cfe5f2022-12-21T22:48:39ZengBMCCancer & Metabolism2049-30022018-11-01611810.1186/s40170-018-0189-0Switch to low-fat diet improves outcome of acute lymphoblastic leukemia in obese miceJonathan Tucci0Waseem Alhushki1Ting Chen2Xia Sheng3Yong-Mi Kim4Steven D. Mittelman5Diabetes and Obesity Program, Center for Endocrinology, Diabetes and Metabolism, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern CaliforniaChildren’s Center for Cancer and Blood Diseases, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern CaliforniaDivision of Pediatric Endocrinology, UCLA Children’s Discovery and Innovation Institute, David Geffen School of Medicine UCLADiabetes and Obesity Program, Center for Endocrinology, Diabetes and Metabolism, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern CaliforniaChildren’s Center for Cancer and Blood Diseases, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern CaliforniaDiabetes and Obesity Program, Center for Endocrinology, Diabetes and Metabolism, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern CaliforniaAbstract Background It is becoming increasingly recognized that weight and nutritional status can impact cancer survival. We have previously shown that obese mice with syngeneic acute lymphoblastic leukemia (ALL) have poorer response to chemotherapy treatment than control mice. We therefore investigated whether dietary intervention could improve outcome from the most common pediatric cancer, ALL. Methods Diet-induced obese (DIO) mice raised on a 60% calories from fat diet and control mice were implanted with syngeneic ALL cells. Some DIO mice were switched to the low-fat control diet. Survival from ALL was assessed without or with chemotherapy treatment starting at the time of the diet switch. Cells from DIO mice before and after diet switch were assessed by FACS for BrdU incorporation and phosphorylation status of AKT, S6K, and EIF2a. Similar experiments were done with human ALL xenografts. Mouse and human ALL cells were cultured in media with 10% or 5% fetal bovine serum, and sensitivity to chemotherapies assessed. Results DIO mice had poorer survival (17%) after vincristine monotherapy than control mice on a 10% low fat diet (42%; n = 12/group; p = 0.09, log rank). However, switching obese mice to the low-fat diet prior to initiation of vincristine led to dramatically improved survival (92%, p < 0.01 vs both other groups). In vitro, FBS restriction made murine and human ALL cells more sensitive to vincristine. Interestingly, while serum restriction enhanced ALL sensitivity to dexamethasone and l-asparaginase, dietary switch did not improve survival of DIO mice treated with either drug in monotherapy. Thus, it appears that dietary intervention has a unique effect to improve ALL cell sensitivity to vincristine in vivo. Conclusions We report herein that a dietary intervention can improve ALL outcome in a preclinical model. Further work is needed to identify the mechanisms of this effect and investigate potential impact on human leukemia in patients.http://link.springer.com/article/10.1186/s40170-018-0189-0ObesityAdipose tissueDietary interventionChemotherapyCaloric restriction |
| spellingShingle | Jonathan Tucci Waseem Alhushki Ting Chen Xia Sheng Yong-Mi Kim Steven D. Mittelman Switch to low-fat diet improves outcome of acute lymphoblastic leukemia in obese mice Cancer & Metabolism Obesity Adipose tissue Dietary intervention Chemotherapy Caloric restriction |
| title | Switch to low-fat diet improves outcome of acute lymphoblastic leukemia in obese mice |
| title_full | Switch to low-fat diet improves outcome of acute lymphoblastic leukemia in obese mice |
| title_fullStr | Switch to low-fat diet improves outcome of acute lymphoblastic leukemia in obese mice |
| title_full_unstemmed | Switch to low-fat diet improves outcome of acute lymphoblastic leukemia in obese mice |
| title_short | Switch to low-fat diet improves outcome of acute lymphoblastic leukemia in obese mice |
| title_sort | switch to low fat diet improves outcome of acute lymphoblastic leukemia in obese mice |
| topic | Obesity Adipose tissue Dietary intervention Chemotherapy Caloric restriction |
| url | http://link.springer.com/article/10.1186/s40170-018-0189-0 |
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