Growth inhibitory effect of Scrophularia oxysepala extract on mouse mammary carcinoma 4T1 cells in vitro and in vivo systems

Biomed Pharmacother. 2017 Jan:85:718-724. doi: 10.1016/j.biopha.2016.11.086. Epub 2016 Dec 4.

Abstract

Introduction: Medical plants have been intensively studied as a source of antitumor compounds. In the present study, we determine the effect of Scrophularia oxysepala on triggering apoptosis and diminishing growth, size and weight of the tumor in the allograft model of Balb/c mice.

Material & methods: The cytotoxic effects of Scrophularia oxysepala extract on 4T1 cells were studied using MTT (3-[4,5-dimethyl-2-thiazolyl]-2, 5 diphenyl tetrazolium bromide) assay and Trypan blue staining. DNA fragmentation assay was done for apoptosis detection. After the establishment of tumor in Balb/c mice, two groups of mice were received the extract at two doses of 50 and 100mg/kg respectively using intraperitoneal injection once every two days for 28 days. In order to assess the induction of apoptosis in cancer cells, the TUNEL assay was carried out in tumoral tissues. Moreover, the Ki67 test was used to evaluate tumor proliferation.

Results: According to the findings, the Scrophularia oxysepala extract inhibited cell growth. In vivo results showed that tumor size in mice treated with the extract was significantly reduced. The weight of tumor mass in treated mice after resection was less than the control group. According to the TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) assay results, the herbal extract induced apoptosis in tumoral cells. Ki67 test also demonstrated that administration of the extract suppressed the growth of tumor cells.

Conclusion: Our data well approved the anti-proliferative effect of Scrophularia oxysepala extract, and clearly showed that, the plant extract can decrease the growth of breast cancer cells in tumor mass. Thus it may represent an ideal therapeutic tool for breast cancer.

Keywords: 4T1; Apoptosis; Cytotoxicity; Mouse breast cancer; Scrophularia oxysepala extract.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 9 / genetics
  • Caspase 9 / metabolism
  • Cell Line
  • Dose-Response Relationship, Drug
  • Female
  • Fibroblasts / drug effects
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Mammary Neoplasms, Animal / drug therapy*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms, Experimental / drug therapy*
  • Phytotherapy
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Scrophularia / chemistry*

Substances

  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Bcl2 protein, mouse
  • Caspase 3
  • Caspase 9