In vivo and In vitro effect of a nutrient mixture on human hepatocarcinoma cell line SK-HEP-1.
Long-term survival of patients with hepatocellular carcinoma (HCC), a common cancer worldwide, remains poor, due to metastasis and recurrence.


OBJECTIVE
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.
Roomi
M W
MW
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050, USA.
Roomi
N W
NW
Kalinovsky
T
T
Niedzwiecki
A
A
Rath
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000494:pharmacology*; D028241:Camellia sinensis; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019587:Dietary Supplements; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D008239:Lysine / Q000494:pharmacology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D011392:Proline / Q000494:pharmacology*; D013662:Tea; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D010936:Plant Extracts; D013662:Tea; D011392:Proline; D020782:Matrix Metalloproteinases; D008239:Lysine; D001205:Ascorbic Acid