Efficacy studies of Sclerotium rolfsii lectin on breast cancer using NOD SCID mouse model

Chem Biol Drug Des. 2018 Aug;92(2):1488-1496. doi: 10.1111/cbdd.13314. Epub 2018 May 31.

Abstract

Expression of altered glycans such as TF, Tn, and sTn antigens has been observed in a number of carcinomas which are targeted in cancer therapy. Sclerotium rolfsii lectin (SRL) is known to recognize TF and its substituted forms. Clinical potential of SRL has been demonstrated by studying its interaction with different types of cancer cells. Here we report, in vitro studies of SRL on breast cancer MDA-MB-468 cells and in vivo studies with MCF-7 xenografts. In vitro growth inhibitory studies of SRL on metastatic triple negative breast cancer MDA-MB-468 cells were performed by MTT assay, flow cytometry, adhesion, and CAM assay. In vivo efficacy studies of SRL were performed using NOD SCID mice bearing MCF-7 xenografts. SRL has strong binding to MDA-MB-468 cells with MFI of 85.5 and has growth inhibitory effect with IC50 of 32 μg/ml at 48 hr. SRL has antiangiogenesis effect and also anti adhesive effect with fibronectin and collagen at 20 μg/ml by 36% and 42%, respectively. In vivo efficacy studies of SRL on NOD SCID mice bearing MCF-7 xenogratfs revealed 61.77% and 75.71% tumor regressing effect, respectively, at 20 and 30 mg/kg body weight without any toxicity. All these results substantiate clinical potential of SRL on breast cancer.

Keywords: MCF-7; MDA-MB-468; Sclerotium rolfsii lectin; breast cancer; efficacy; tumor regression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Basidiomycota / metabolism*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Models, Animal
  • Female
  • Kidney / drug effects
  • Kidney / pathology
  • Lectins / pharmacology
  • Lectins / therapeutic use*
  • Liver / drug effects
  • Liver / pathology
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neovascularization, Physiologic / drug effects
  • Transplantation, Heterologous

Substances

  • Antineoplastic Agents
  • Lectins