Cytotoxic activity of maytanprine isolated from Maytenus diversifolia in human leukemia K562 cells.
We examined the cytotoxic effect of maytanprine isolated from the methanol extract of Maytenus diversifolia on human leukemia K562 cells using a flow cytometer and compared its cytotoxicity with that of maytansine, a potent cytotoxic maytansinoid. Maytanprine at concentrations of 0.03 nM or more (up to 1 nM) attenuated cell growth with decreasing cell viability and increased the population of shrunken cells in a concentration-dependent manner. Complete inhibition of growth by maytanprine was observed at concentrations of 0.3 nM or more. The compound at 0.03 nM markedly decreased the population at G0G1 phase in the cell cycle, but only slightly decreased that in the G2M phase, suggesting the possibility that it inhibits or delays cell division, and increased the population of cells with hypodiploidal DNA (apoptotic cells). The potency of maytanprine in inhibiting cell growth was greater than that of maytansine, although the inhibitory action of maytanprine was similar to that of maytansine. The results suggest that maytanprine exerts a potent inhibitory action on the growth of human leukemia K562 cells. M. diversifolia is one natural source of maytanprine, which is more cytotoxic than maytansine.
Nakao
Hiromi
H
Laboratories of Cell Signaling and Bioorganic Chemistry, Faculty of Integrated Arts and Sciences, The University of Tokushima, Tokushima, Japan.
Senokuchi
Kaori
K
Umebayashi
Chisato
C
Kanemaru
Kaori
K
Masuda
Toshiya
T
Oyama
Yasuo
Y
Yonemori
Shigetomo
S
D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D020014:K562 Cells; D008453:Maytansine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology*
D000970:Antineoplastic Agents; D008453:Maytansine; C033351:maytanprine