The cytotoxicity of naturally occurring styryl lactones.
We extracted and isolated three natural styryl lactones from Goniothalamus griffithii Hook f. Thoms and investigated their cytotoxicity on a panel of three hepatocyte cell lines, HepG2, drug resistant HepG2 (HepG2-R) and primary cultured normal mice hepatocyte in order to find candidates of potential anti-cancer drugs which have low toxicity on normal cells and high effect on tumors or drug resistant tumors. All the three styryl lactones showed evident cytotoxic activities on both HepG2 and HepG2-R cell lines; however, gonithalamin and goniodiol shows less toxicity on normal mice hepatocyte as the IC(50) values of them on normal mice hepatocyte were about three times of that on HepG2. Morphological observation and cell cycle analysis were employed to elucidate the mechanisms of cytotoxicity of the tested compounds. Many apoptotic cells were observed in gonithalamin- and altholactone-treated cells, whereas, cells with chromosomes gathered at the equator were easily found in goniodiol-treated cultures. The analysis of cell cycle showed that G(2)/M arrest contributed to goniothalimin- and gonidiol-caused cell death and apoptosis was the cause of gonithalamin- and altholactone-induced cell death. Our results suggest that the three styryl lactones may be prospectively developed into anti-tumor drugs, especially on treating drug-resistance tumor after structure modification.
Tian
Ze
Z
Institute of Medicinal Plant, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, PR China.
Chen
Sibao
S
Zhang
Yaòu
Y
Huang
Minghui
M
Shi
Lin
L
Huang
Feng
F
Fong
Chichun
C
Yang
Mengsu
M
Xiao
Peigen
P
D000818:Animals; D029061:Annonaceae / Q000737:chemistry; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D005434:Flow Cytometry / Q000379:methods; D005663:Furans / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D006248:Harringtonines / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D051379:Mice; D011753:Pyrones / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods
D005663:Furans; D006248:Harringtonines; D007783:Lactones; D011753:Pyrones; C459359:altholactone; C446739:goniodiol; C509543:gonithalamin; C062500:harringtonin