Table 2 ∣.
Fasting or FMDs in cancer mouse models
Cancer model | Mouse strains | Dietary regimen | Main findings | Refs |
---|---|---|---|---|
Metastatic neuroblastoma model (intravenous cancer cell injection): NXS2 (mouse neuroblastoma allograft) | A/J, CD-1 and athymic nude mice | 48 h fasting (water only) given once prior to high-dose etoposide injection versus ad libitum diet | Fasting cycles reduced toxicity of high-dose etoposide in mice but did not reduce etoposide activity profile against neuroblastoma allografts | 12 |
Subcutaneous tumour models: 4T1 (mouse breast cancer allograft), B16 (mouse melanoma allograft), GL26 (mouse glioma allograft), ACN (human neuroblastoma xenograft), MDA-MB-231 (human breast cancer xenograft) and OVCAR3 (human ovarian cancer xenograft). Metastatic cancer models (intravenous cancer cell injection): 4T1 (allograft), B16 (allograft), NXS2 (mouse neuroblastoma allograft) and Neuro-2a (mouse neuroblastoma allograft) |
BALB/c, C57Bl/6 and athymic nude mice | 48 h fasting (water only) given once a week between 1 and 4 times, 24 h prior to and 24 h after chemotherapy injection versus ad libitum diet | Fasting cycles combined with doxorubicin or cyclophosphamide were superior to each treatment alone in retarding the growth of subcutaneously growing tumours and extending survival in metastatic models of breast cancer, melanoma and neuroblastoma | 11 |
Subcutaneous tumour models:ZL55 (human mesothelioma xenograft) and A549 (human lung cancer xenograft) | Nude mice | 48 h fasting (water only) given once a week for 3 times, 32 h prior to and 16 h after cisplatin injection versus ad libitum diet | Fasting sensitized human mesothelioma and lung cancer xenografts to cisplatin. Complete remissions were observed in only the combination treatments (in 40–60% of the mice) | 59 |
Subcutaneous tumour models: H2133 (human lung cancer xenograft) and HCT116 (human colorectal cancer xenograft) | Athymic nude mice | 48 h fasting (water only) given once a week for 3 times during daily treatment with crizotinib or regorafenib versus ad libitum diet | Fasting improved the clinical activity of crizotinib and of regorafenib and boosted their ability to block MAPK signalling | 17 |
Subcutaneous tumour model: CT26 (mouse colon cancer allograft) | BALB/c mice | 48 h fasting (water only) given once a week for 2 times, 24 h prior to and 24 h after oxaliplatin injection versus ad libitum diet | Fasting potentiated the anticancer effects of oxaliplatin, exerted anti-Warburg effects and promoted oxidative stress and apoptosis in cancer cells | 50 |
Subcutaneous tumour models: 4T1 (mouse breast cancer allograft), B16 (mouse melanoma allograft) and MCF7 (human breast cancer xenograft) | BALB/c, C57Bl/6 and athymic nude mice | 48–60 h fasting (water only) or a 96 h FMD given once a week for 2 to 4 times versus ad libitum diet. Animals were injected with chemotherapy at the end of each fasting and/or FMD cycle | An FMD was as effective as fasting at reducing tumour progression when combined with doxorubicin or cyclophosphamide. The FMD downregulated HO1 expression in cancer cells, expanded lymphoid progenitors in the bone marrow and boosted anticancer immunity | 124 |
Subcutaneous tumour model: MCA205 (mouse fibrosarcoma allograft) | C57Bl/6 and athymic nude mice | 48 h fasting (water only) given once versus ad libitum diet. Animals were injected with mitoxantrone or oxaliplatin at the end of fasting | Fasting and calorie restriction mimetics improved the efficacy of chemotherapy in an immune system-dependent and autophagy-dependentfashion. Autophagy was shown to allowfor optimal release of ATP from dying cancer cells, leading to the depletion of intratumoural regulatory T cells and thereby improving the anticancer immune response | 56 |
B-ALL, T-ALL and AML models: Lin− bone marrow cells were infected with retroviruses expressing MYC–IRES–GFP (B-ALL), NOTCH1–IRES–GFP (T-ALL) or MLL–AF9–IRES-YFP (AML) and subsequently transplanted into irradiated mice | C57Bl/6 mice | 1 day of fasting followed by 1 day of feeding, for a total of 6 cycles starting from day 2 after transplantation versus ad libitum diet | Fasting inhibited B-ALL and T-ALL development by upregulation of the leptin receptor and its downstream signalling. AML growth was not affected | 55 |
Subcutaneous tumour model: CT26 (mouse colon cancer allograft) | BALB/c mice | 24 h fasting on alternate days for 2 weeks | Fasting inhibited colon cancer growth and decreased the production of extracellular adenosine by cancer cells by supressing CD73 expression | 60 |
Subcutaneous tumour model: BxPC-3 (human pancreatic cancer xenograft) | Nu/Nu nude mice | 24 h fasting (water only) before the administration of gemcitabine | Fasting before gemcitabine injection delayed pancreatic cancer progression and increased tumour ENT1 levels | 128 |
p53+/− mice; these mice are prone to spontaneous neoplasms (most commonly sarcoma and lymphoma) | C57Bl/6 mice | 24 h fasting (water only) once a week | Fasting delayed the onset of tumours in adult mice and lowered leptin and IGF1 compared with mice fed ad libitum | 89 |
Age-associated lymphoma | OF-1 mice | Alternate-day fasting initiated at 8 months of age through a 4-month period | Fasting reduced the incidence of lymphoma (0% versus 33% for controls), decreased the mitochondrial generation of ROS and increased spleen mitochondrial SOD activity | 145 |
B-ALL, B cell acute lymphoblastic leukaemia; ENT 1, equilibrative nucleoside transporter 1; FMD, fasting-mimicking diet; GFP, green fluorescent protein; HO1, haem oxygenase 1; ROS, reactive oxygen species; SOD, superoxide dismutase; T-ALL, T cell acute lymphoblastic leukaemia; YFP, yellow fluorescent protein.