Caloric restriction counteracts chemotherapy-induced inflammation and increases response to therapy in a triple negative breast cancer model

Brittany A. Simone, Ajay Palagani, Kimberly Strickland, Kevin Ko, Lianjin Jin, Meng Kieng Lim, Tu D. Dan, Mak Sarich, Daniel A. Monti, Massimo Cristofanilli, Nicole L. Simone

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Triple negative breast cancer (TNBC) is a heterogeneous disease that has no available targeted therapies. Previously, we have shown that caloric restriction (CR) can augment the effects of radiation therapy in a TNBC mouse model. To build upon this, we now present data regarding the combination of chemotherapy and CR in the same 4T1 model. Chemotherapy can induce inflammation that breeds resistance to therapy. We propose CR as a mechanism to decrease chemotherapy-induced inflammation and increase efficacy of therapy. 12-week old Balb/c mice were orthotopically injected with a syngeneic triple negative breast cancer cell line (4T1) and were treated in one of six cohorts: ad lib fed (AL), 30% reduction in calorie intake (CR), cisplatin or docetaxol alone or a combination CR+cisplatin/docetaxol. Mice in the cohorts receiving chemotherapy+CR had longer overall survival (12 ± 2 days) as compared to the AL group. These mice also demonstrated less lung metastases at the final time point of in vivo imaging. In addition, downregulation of the IGF-1R and IRS signaling pathways were noted most significantly in those mice receiving combination therapy. Lastly, serum from these mice demonstrated an increase in inflammatory cytokines TNF-α and IL-1β in response to chemotherapy alone. This increase was dampened by the addition of CR. Taken together, these data suggest that while chemotherapy is effective in TNBC, it can cause inflammation, which can be a driver of resistance to therapy. This chemotherapy-induced inflammation can be reversed with the use of CR as a nontoxic adjunct to treatment.

Original languageEnglish (US)
Pages (from-to)1536-1544
Number of pages9
JournalCell Cycle
Volume17
Issue number13
DOIs
StatePublished - Jul 3 2018

Fingerprint

Triple Negative Breast Neoplasms
Caloric Restriction
Inflammation
Drug Therapy
docetaxel
Cisplatin
Therapeutics
Combination Drug Therapy
Interleukin-1
Radiotherapy
Down-Regulation
Cytokines
Neoplasm Metastasis
Cell Line
Lung
Serum

Keywords

  • adipokines
  • breast cancer
  • chemotherapy
  • Diet
  • inflammation

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Caloric restriction counteracts chemotherapy-induced inflammation and increases response to therapy in a triple negative breast cancer model. / Simone, Brittany A.; Palagani, Ajay; Strickland, Kimberly; Ko, Kevin; Jin, Lianjin; Lim, Meng Kieng; Dan, Tu D.; Sarich, Mak; Monti, Daniel A.; Cristofanilli, Massimo; Simone, Nicole L.

In: Cell Cycle, Vol. 17, No. 13, 03.07.2018, p. 1536-1544.

Research output: Contribution to journalArticle

Simone, BA, Palagani, A, Strickland, K, Ko, K, Jin, L, Lim, MK, Dan, TD, Sarich, M, Monti, DA, Cristofanilli, M & Simone, NL 2018, 'Caloric restriction counteracts chemotherapy-induced inflammation and increases response to therapy in a triple negative breast cancer model', Cell Cycle, vol. 17, no. 13, pp. 1536-1544. https://doi.org/10.1080/15384101.2018.1471314
Simone, Brittany A. ; Palagani, Ajay ; Strickland, Kimberly ; Ko, Kevin ; Jin, Lianjin ; Lim, Meng Kieng ; Dan, Tu D. ; Sarich, Mak ; Monti, Daniel A. ; Cristofanilli, Massimo ; Simone, Nicole L. / Caloric restriction counteracts chemotherapy-induced inflammation and increases response to therapy in a triple negative breast cancer model. In: Cell Cycle. 2018 ; Vol. 17, No. 13. pp. 1536-1544.
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AU - Simone, Brittany A.

AU - Palagani, Ajay

AU - Strickland, Kimberly

AU - Ko, Kevin

AU - Jin, Lianjin

AU - Lim, Meng Kieng

AU - Dan, Tu D.

AU - Sarich, Mak

AU - Monti, Daniel A.

AU - Cristofanilli, Massimo

AU - Simone, Nicole L.

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AB - Triple negative breast cancer (TNBC) is a heterogeneous disease that has no available targeted therapies. Previously, we have shown that caloric restriction (CR) can augment the effects of radiation therapy in a TNBC mouse model. To build upon this, we now present data regarding the combination of chemotherapy and CR in the same 4T1 model. Chemotherapy can induce inflammation that breeds resistance to therapy. We propose CR as a mechanism to decrease chemotherapy-induced inflammation and increase efficacy of therapy. 12-week old Balb/c mice were orthotopically injected with a syngeneic triple negative breast cancer cell line (4T1) and were treated in one of six cohorts: ad lib fed (AL), 30% reduction in calorie intake (CR), cisplatin or docetaxol alone or a combination CR+cisplatin/docetaxol. Mice in the cohorts receiving chemotherapy+CR had longer overall survival (12 ± 2 days) as compared to the AL group. These mice also demonstrated less lung metastases at the final time point of in vivo imaging. In addition, downregulation of the IGF-1R and IRS signaling pathways were noted most significantly in those mice receiving combination therapy. Lastly, serum from these mice demonstrated an increase in inflammatory cytokines TNF-α and IL-1β in response to chemotherapy alone. This increase was dampened by the addition of CR. Taken together, these data suggest that while chemotherapy is effective in TNBC, it can cause inflammation, which can be a driver of resistance to therapy. This chemotherapy-induced inflammation can be reversed with the use of CR as a nontoxic adjunct to treatment.

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