Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy.
Short-term starvation (or fasting) protects normal cells, mice, and potentially humans from the harmful side effects of a variety of chemotherapy drugs. Here, we show that treatment with starvation conditions sensitized yeast cells (Saccharomyces cerevisiae) expressing the oncogene-like RAS2(val19) to oxidative stress and 15 of 17 mammalian cancer cell lines to chemotherapeutic agents. Cycles of starvation were as effective as chemotherapeutic agents in delaying progression of different tumors and increased the effectiveness of these drugs against melanoma, glioma, and breast cancer cells. In mouse models of neuroblastoma, fasting cycles plus chemotherapy drugs--but not either treatment alone--resulted in long-term cancer-free survival. In 4T1 breast cancer cells, short-term starvation resulted in increased phosphorylation of the stress-sensitizing Akt and S6 kinases, increased oxidative stress, caspase-3 cleavage, DNA damage, and apoptosis. These studies suggest that multiple cycles of fasting promote differential stress sensitization in a wide range of tumors and could potentially replace or augment the efficacy of certain chemotherapy drugs in the treatment of various cancers.
Andrus Gerontology Center, Department of Biological Sciences, Norris Cancer Center, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA.
Changhan
C
Lee
Lizzia
L
Raffaghello
Sebastian
S
Brandhorst
Fernando M
FM
Safdie
Giovanna
G
Bianchi
Alejandro
A
Martin-Montalvo
Vito
V
Pistoia
Min
M
Wei
Saewon
S
Hwang
Annalisa
A
Merlino
Laura
L
Emionite
Rafael
R
de Cabo
Valter D
VD
Longo
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001835:Body Weight; D045744:Cell Line, Tumor; D005215:Fasting / Q000502:physiology*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy*; D009447:Neuroblastoma / Q000188:drug therapy; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents