4'-O-Alkyaloenin derivatives and their sulfates directed toward overcoming multidrug resistance in tumor cells.

Abstract

The cytotoxic effects on HCT 116, Hep G2 and HCT 116/VCR 100-1-1 cell lines of synthetic 4'-O-alkylaloenins (2-17), 4'-O-benzylaloenin (18) and 4'-O-allylaloenin (19) were examined by MTT assay, and compared with that of aloenin (1) isolated from Aloe arborescens Mill. Var. natalensis Berger which showed no marked effect (IC50 value: > 100 microM). The cytotoxic effects of 4'-O-alkylaloenin sulfates (21-29) were also examined on the same cell lines. The introduction of a longer alkyl group at the O-4' position of 1 resulted in a higher cytotoxic action on HCT 116 and Hep G2 cells. Among 4'-O-alkylaloenins 2-17, 4'-O-tetradecylaloenin 14 was the most cytotoxic to both on HCT 116 cells (IC50 value: 5.3+/-2.3 microM) and Hep G2 cells (IC50 value: 4.0+/-0.6 microM). Also among 4'-O-alkylaloenin sulfates 21-29, 4'-O-dodecylaloenin sulfate 29 was the most cytotoxic to both on HCT 116 (IC50 value: 4.8+/-0.2 microM) and Hep G2 cells (IC50 value: 4.0+/-0.5 microM). 4'-O-Alkylaloenins 7-14 and 4'-O-alkylaloenin sulfates 24-29 were also cytotoxic to Hep G2 and HCT 116/VCR 100-1-1 cell lines, which overexpress P-glycoprotein, as well as HCT 116 cell lines which scarcely express it.

• Authors: Guang-Zhu Jin, Hong-Ji Quan, Jyunichi Koyanagi, Kazuhiro Takeuchi, Yoshihiko Miura, Fusao Komada, Setsuo Saito
• Journal: Cancer letters (Cancer Lett) Vol. 218 Issue 1 Pg. 15-20 (Jan 31 2005) ISSN: 0304-3835 [Print] Ireland
• PMID: 15639336 (Publication Type: Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Coloring Agents
• Glucosides
• Sulfates
• Tetrazolium Salts
• Thiazoles
• aloenin
• thiazolyl blue

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• Carcinoma, Hepatocellular (pathology)
• Colorectal Neoplasms
• Coloring Agents (chemistry)
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Drug Screening Assays, Antitumor
• Glucosides (chemistry, pharmacology)
• Humans
• Liver Neoplasms (pathology)
• Sulfates
• Tetrazolium Salts (chemistry)
• Thiazoles (chemistry)
• Tumor Cells, Cultured