Inhibition of breast tumor growth in mice after treatment with ceramide analog 315

Anticancer Drugs. 2018 Oct;29(9):898-903. doi: 10.1097/CAD.0000000000000675.

Abstract

The aim of this study was to evaluate the anticancer and antitumor activities of ceramide analog 315 in nude mice. Nude mice (n=10) were injected bilaterally with 5×10 MDA-MB-231 cells on each side. Tumors were allowed to form for 2 weeks. The mice were then divided into two groups (n=5 in each group). The control group mice were injected with 25 μl of dimethyl sulfoxide and the treatment group mice were injected with 10 mg/kg of analog 315 (in dimethyl sulfoxide, 25 μl volume) every day for a period of 3 weeks. Animal weights and tumors were measured every week for 3 weeks. At the end of the experimental period, control animals had retained excess fluid, and showed larger tumor sizes compared with the treated group (2.95 vs. 1.67 g). A 45% reduction in tumor size and 80% decrease in tumor volume were observed in the treatment group. There was a significant increase in the weights of liver (10%) and spleen (19%) between the control and treated animals. Hematoxylin and Eosin staining of MDA-MB-231 tumor sections revealed more acellular necrotic regions in tumors from the treatment groups compared with the ones from the control group. Ki67, a proliferation marker was higher in number in control tumor section (71.8±12.8) compared to the treatment tumor section (37.4±10.4) (P<0.001). Photomicrographs showed metastatic tumor burden in kidney, lungs, and spleen collected from the control group mice bearing MDA-MB-231 tumors. Treatment group mice showed normal microscopic tissue architecture. Overall, our study showed tumor growth inhibition and antimetastatic effects for the novel ceramide analog 315.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Ceramides / chemistry
  • Ceramides / pharmacology*
  • Dimethyl Sulfoxide / administration & dosage
  • Female
  • Humans
  • Ki-67 Antigen / metabolism
  • Kidney Neoplasms / prevention & control
  • Kidney Neoplasms / secondary
  • Lung Neoplasms / prevention & control
  • Lung Neoplasms / secondary
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis / prevention & control
  • Splenic Neoplasms / prevention & control
  • Splenic Neoplasms / secondary
  • Tumor Burden / drug effects*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Ceramides
  • Ki-67 Antigen
  • Dimethyl Sulfoxide