Cytotoxic oleane-type triterpene saponins from Glochidion eriocarpum.
The anticancer activity of ten compounds from the aerial parts of Glochidion eriocarpum were evaluated on two human cancer cell lines, HL-60 and HCT-116. Compounds 1-4 displayed highly potent cytotoxic activity on the HCT-116 cancer cell line with IC(50) values ranging of 0.41∼1.16 μM. Compounds 1-4 significantly inhibited the HL-60 cell line with IC(50) values ranging of 4.51∼6.33 μM. These results suggested that the benzoyl group at the C-22 position in oleane-type triterpene saponins was essential for cytotoxicity towards tumor cells. Moreover, compounds 2 and 3 showed more potent cytotoxicity than compounds 1 and 4 against HL-60 and HCT-116 cells. With respect to the mechanism underlying cytotoxicity, compounds 1-4 increased chromatin condensation, a typical apoptotic characteristic in HL-60 and HCT-116 cells. In the mechanism of apoptosis induction, compounds 1-4 reduced Bcl-2 expression, whereas the expression of Bax was increased compared to controls in HCT-116 cells. In addition, compounds 1-4 decreased the level of procaspase-3. The cleavage of poly (ADP-ribose) polymerase (PARP), a vital substrate of effector caspase, was observed in HCT-116 cells. Furthermore, the induction of apoptosis was also accompanied by an activation of extracellular signal-regulated kinase (ERK) and p38 kinase in HCT-116 cells. These findings provide evidence demonstrating that the pro-apoptotic effects of compounds 1-4 are mediated through the activation of ERK and p38 in HCT-116 cells.
College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea.
Nguyen Xuan
NX
Nhiem
Vu Kim
VK
Thu
Phan
P
Van Kiem
Chau
C
Van Minh
Bui Huu
BH
Tai
Tran Hong
TH
Quang
Nguyen Xuan
NX
Cuong
Pham Hai
PH
Yen
Hye-Jin
HJ
Boo
Jung-Il
JI
Kang
Hee-Kyoung
HK
Kang
Young Ho
YH
Kim
D017209:Apoptosis / Q000187:drug effects; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D019665:Euphorbiaceae / Q000737:chemistry; D045325:HCT116 Cells; D018922:HL-60 Cells; D006801:Humans; D035261:Plant Components, Aerial / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*
D003603:Cytotoxins; D010936:Plant Extracts; D012503:Saponins; D014315:Triterpenes