Reversal of multidrug resistance in human carcinoma cell line by agosterols, marine spongean sterols

✍ Scribed by Shunji Aoki; Andi Setiawan; Yasuhiro Yoshioka; Kouichi Higuchi; Ritsuko Fudetani; Zhe-Sheng Chen; Tomoyuki Sumizawa; Shin-ichi Akiyama; Motomasa Kobayashi

• Publisher: Elsevier Science
• Year: 1999
• Tongue: French
• Weight: 531 KB
• Volume: 55
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(99)00870-4

✦ Synopsis

We have isolated agosterol A (1) from a marine sponge of Spongia sp. as a reversing substance to multidrug resistance (MDR) in human carcinoma cell lines, KB-C2 and KB-CV60, overexpressing P-glycoprotein and MRP, respectively. Further investigation led us to isolate analogous sterols, agosterols B (2), C (5), A 4 (7), D 2 (10), A 5 (13) and C 6 ( 14) from the same sponge and determine their structures. From the structure-activity relationship study, each of the 3,4,6-acetoxyl groups and 11,22-hydroxyl groups was elucidated to be crucial for reversing MDR in tumor cells.