Effective melanoma inhibition by synthetic pentacyclic triterpenoid 2-(3-phenylprop-2-en-1-ylidene)-22β-hydroxy-3-oxoolean-12-en-28-oic acid: an in vitro and in vivo study.

Abstract

The C-2 arylidene analog (compound 3) of pentacyclic triterpenoid Lantadene A (compound 1) was synthesized and evaluated by the National Cancer Institute, USA, for in vitro cytotoxicity against a panel of melanoma cancer cell lines: LOX IMVI, MALME-3M, M14, MDA-MB-435, SK-MEL-2, SK-MEL-28, SK-MEL-5, UACC-257 UACC-62 and B16F10. Compound 3 showed enhanced cytotoxicity compared with compound 1 and the standard drug cisplatin. At the same time, compound 3 showed selective toxicity toward cancer cells and was inactive (i.e., nontoxic) against normal cells (VERO). Compound 3 induced sub-G1 cell cycle arrest and apoptosis in B16F10 cells by down-regulating NF-κB, c-jun, Bcl-2, and by activating caspase-3 and Bax expression. Compound 3 also demonstrated beneficial effects in a clinically relevant B16F10 allograft mice model, with significant reduction of tumor growth/tumor weight in vivo. Compound 3 improved the survival rate in comparison to the control group and the cisplatin group. At the same time, compound 3 had a better safety profile than cisplatin in terms of hematological parameters and liver enzyme levels.

• Authors: Navin Kumar Tailor, Hong Boon Lee, Manu Sharma
• Journal: Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer (J Environ Pathol Toxicol Oncol) Vol. 32 Issue 1 Pg. 59-72 ( 2013) ISSN: 2162-6537 [Electronic] United States
• PMID: 23758153 (Publication Type: Comparative Study, Journal Article)

Chemical References

• NF-kappa B
• Pentacyclic Triterpenes
• Proto-Oncogene Proteins c-bcl-2
• Proto-Oncogene Proteins c-jun
• bcl-2-Associated X Protein
• Oleanolic Acid
• rehmannic acid
• Caspase 3

Topics

• Animals
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cells, Cultured
• Chlorocebus aethiops
• DNA Fragmentation (drug effects)
• Disease Models, Animal
• In Vitro Techniques
• Male
• Melanoma (drug therapy, mortality, pathology)
• Mice
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• Oleanolic Acid (analogs & derivatives, pharmacology, therapeutic use)
• Pentacyclic Triterpenes (pharmacology, therapeutic use)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Proto-Oncogene Proteins c-jun (metabolism)
• Skin Neoplasms (drug therapy, mortality, pathology)
• Survival Rate
• Transplantation, Homologous
• Vero Cells
• bcl-2-Associated X Protein (metabolism)