JOURNAL ARTICLE

Oridonin induced A375-S2 cell apoptosis via bax-regulated caspase pathway activation, dependent on the cytochrome c/caspase-9 apoptosome

Chun-Ling Zhang, Li-Jun Wu, Shin-Ichi Tashiro, Satoshi Onodera, Takashi Ikejima
Journal of Asian Natural Products Research 2004, 6 (2): 127-38
15008459
Two diterpenoids, oridonin (1) and ponicidin (2), were isolated from the 95% ethanol extract of Rabdosia rubescens and were evaluated for antiproliferative activity on cancer cells and human peripheral blood mononuclear cells (PBMC) in vitro. Oridonin has much more potent cytotoxic effects on four tumor cells (human melanoma A375-S2, human cervical cancer HeLa, human breast adenocarcinoma MCF-7, murine fibrosarcoma L929) than does ponicidin. The growth-inhibitory activity of oridonin for A375-S2 cells was more potent than that for the other cell lines, with an IC50 of 15.1 +/- 1.2 micromol L(-1). Treatment with oridonin (34.3 micromol L(-1)) for 12 h significantly inhibited A375-S2 cell growth, and showed weaker cytotoxicity against PBMC. By contrast, ponicidin markedly inhibited the growth of PBMC under the same conditions. When caspases-3 and -8 were activated at early stages after treatment of A375-S2 cells with oridonin (34.3 micromol L(-1)), apoptotic bodies were formed, nuclear damage was observed by Hoechst 33258 staining and DNA fragmentation was exhibited. In addition, oridonin increased the expression of the apoptosis inducer, Bax, promoted the release of cytochrome c without affecting Bcl-2 expression, and activated down-stream caspase-9 in the mitochondrial pathway. These observations indicated that an appropriate dose of oridonin gave an initial premitochondrial phase that involved the Bcl-2 family of the pro-apoptotic protein Bax that required the participation of caspase-9 and caspase-3. However, on treatment with oridonin (137.4 micromol L(-1)) for 12 h, the majority of A375-S2 cells underwent necrosis as measured by an LDH activity-based assay. Our results suggest that oridonin induces A375-S2 cell death on the balance of apoptosis and necrosis.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
15008459
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"