We have recently reported that Ginsenoside Rh2 （G- Rh2） induces the activation of two initiator caspases, caspase-8 and caspase-9 in human cancer cells. How- ever, the molecular mechanism of its death-inducing funct...We have recently reported that Ginsenoside Rh2 （G- Rh2） induces the activation of two initiator caspases, caspase-8 and caspase-9 in human cancer cells. How- ever, the molecular mechanism of its death-inducing function remains unclear. Here we show that G-Rh2 stimulated the activation of both caspase-8 and cas- pase-9 simultaneously in HeLa cells. Under G-Rh2 treatment, membrane death receptors Fas and TNFR1 are remarkably upregulated. However, the induced expression of Fas but not TNFR1 was contributed to the apoptosis process, Moreover, significant increases in Fas expression and caspase-8 activity temporally coin- cided with an increase in p53 expression in p53-non- mutated HeLa and SK-HEP-1 cells upon G-Rh2 treat- ment. In contrast, Fas expression and caspase-8 activity remained constant with G-Rh2 treatment in p53-mutated SW480 and PC-3 cells. In addition, siRNA-mediated knockdown of p53 diminished G-Rh2-induced Fas expression and caspase-8 activation, These results indicated that G-Rh2-triggered extrinsic apoptosis relies on p53-mediated Fas over-expression. In the intrinsic apoptotic pathway, G-Rh2 induced strong and immedi- ate translocation of cytosolic BAK and BAX to the mitochondria, mitochondrial cytochrome c release, and subsequent caspase-9 activation both in HeLa and in SW480 ceils, p53-mediated Fas expression and sub- sequent downstream caspase-8 activation as well as p53-independent caspase-9 activation all contribute to the activation of the downstream effector caspase-3/-7, leading to tumor cell death. Taken together, we suggest that G-Rh2 induces cancer cell apoptosis in a multi-path manner and is therefore a promising candidate for anti- tumor drug development.展开更多
Five minor compounds isolated from the leaves of Panax ginseng C. A. Meyer were characterized as 20（R）-protopanaxatriol （1）, daucosterin （2）, 3β, 12β-dihydroxy-dammar-20 （22）, 24-diene-3-O-β-D-glucopyranosi...Five minor compounds isolated from the leaves of Panax ginseng C. A. Meyer were characterized as 20（R）-protopanaxatriol （1）, daucosterin （2）, 3β, 12β-dihydroxy-dammar-20 （22）, 24-diene-3-O-β-D-glucopyranoside （3）, 20 （R）-protopanaxadiol-3-O-β-D-glucopyranoside （4） and ginsenoside-Rh2 （5）, respectively, on the basis of spectral analyses and chemical evidence. The two new saponins, 3 and 4, were named as ginsenoside-Rh3 and 20（R）-ginsenoside-Rh2.Nine other major saponins obtained simultaneously were identical with ginsenoside-Rh1（6）,-Rg3 （7）, -Rg2 （8）, -Rg1 （9）,-Re（10）,-Rd （11）, -Rc （12）, -Rb2（13） and Rb1 （14）, respectively.展开更多
文摘We have recently reported that Ginsenoside Rh2 （G- Rh2） induces the activation of two initiator caspases, caspase-8 and caspase-9 in human cancer cells. How- ever, the molecular mechanism of its death-inducing function remains unclear. Here we show that G-Rh2 stimulated the activation of both caspase-8 and cas- pase-9 simultaneously in HeLa cells. Under G-Rh2 treatment, membrane death receptors Fas and TNFR1 are remarkably upregulated. However, the induced expression of Fas but not TNFR1 was contributed to the apoptosis process, Moreover, significant increases in Fas expression and caspase-8 activity temporally coin- cided with an increase in p53 expression in p53-non- mutated HeLa and SK-HEP-1 cells upon G-Rh2 treat- ment. In contrast, Fas expression and caspase-8 activity remained constant with G-Rh2 treatment in p53-mutated SW480 and PC-3 cells. In addition, siRNA-mediated knockdown of p53 diminished G-Rh2-induced Fas expression and caspase-8 activation, These results indicated that G-Rh2-triggered extrinsic apoptosis relies on p53-mediated Fas over-expression. In the intrinsic apoptotic pathway, G-Rh2 induced strong and immedi- ate translocation of cytosolic BAK and BAX to the mitochondria, mitochondrial cytochrome c release, and subsequent caspase-9 activation both in HeLa and in SW480 ceils, p53-mediated Fas expression and sub- sequent downstream caspase-8 activation as well as p53-independent caspase-9 activation all contribute to the activation of the downstream effector caspase-3/-7, leading to tumor cell death. Taken together, we suggest that G-Rh2 induces cancer cell apoptosis in a multi-path manner and is therefore a promising candidate for anti- tumor drug development.
文摘Five minor compounds isolated from the leaves of Panax ginseng C. A. Meyer were characterized as 20（R）-protopanaxatriol （1）, daucosterin （2）, 3β, 12β-dihydroxy-dammar-20 （22）, 24-diene-3-O-β-D-glucopyranoside （3）, 20 （R）-protopanaxadiol-3-O-β-D-glucopyranoside （4） and ginsenoside-Rh2 （5）, respectively, on the basis of spectral analyses and chemical evidence. The two new saponins, 3 and 4, were named as ginsenoside-Rh3 and 20（R）-ginsenoside-Rh2.Nine other major saponins obtained simultaneously were identical with ginsenoside-Rh1（6）,-Rg3 （7）, -Rg2 （8）, -Rg1 （9）,-Re（10）,-Rd （11）, -Rc （12）, -Rb2（13） and Rb1 （14）, respectively.
