In vivo and In vitro effect of a nutrient mixture on human hepatocarcinoma cell line SK-HEP-1

Exp Oncol. 2010 Jul;32(2):84-91.

Abstract

Long-term survival of patients with hepatocellular carcinoma (HCC), a common cancer worldwide, remains poor, due to metastasis and recurrence.

Aim: To investigate the effect of a novel nutrient mixture (NM) containing ascorbic acid, lysine, proline, and green tea extract on human HCC cell line Sk-Hep-1 In vivo and In vitro.

Methods: After one week of isolation, 5-6 week old male athymic nude mice were inoculated with 3 x 10(6) SK-Hep-1 cells subcutaneously and randomly divided into two groups; group A was fed a regular diet and group B a regular diet supplemented with 0.5% NM. Four weeks later, the mice were sacrificed and their tumors were excised, weighed and processed for histology. We also tested the effect of NM In vitro on SK-Hep-1 cells, measuring cell proliferation by MTT assay, invasion through Matrigel, apoptosis by green caspase detection kit, MMP secretion by zymography, and morphology by H&E staining.

Results: NM inhibited tumor weight and burden of SK-Hep-1 xenografts by 42% and 33% respectively. In vitro , NM exhibited 33% toxicity over the control at 500 and 1,000 microg/ml concentration. Zymography demonstrated MMP-2 and MMP-9 secretion which was inhibited by NM in a dose dependent fashion, with virtual total inhibition at 1000 microg/ml. Invasion through Matrigel was inhibited at 100, 500 and 1,000 microg/ml by 53%, 83% and 100% respectively. NM induced slight apoptosis at 100 microg/ml, and profound apoptosis at 500 microg/ml and 1000 microg/ml concentration.

Conclusions: These results suggest that NM has therapeutic potential in treatment of HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Ascorbic Acid / pharmacology*
  • Camellia sinensis
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dietary Supplements
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / pathology
  • Lysine / pharmacology*
  • Male
  • Matrix Metalloproteinases / drug effects
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / pathology
  • Plant Extracts / pharmacology*
  • Proline / pharmacology*
  • Tea
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Plant Extracts
  • Tea
  • Proline
  • Matrix Metalloproteinases
  • Lysine
  • Ascorbic Acid