Diterpenoid Tanshinones, the extract from Danshen (Radix Salviae Miltiorrhizae) induced apoptosis in nine human cancer cell lines

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• 作者：Shen Li^a ; ^b ; Lou Zhaohuan^c ; Zhang Guangshun^d ; Xu Guanhua^e ; Zhang Guangji^d ; ^{zgj@zcmu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Tanshinone ; Salviae Miltiorrhiza ; Antineoplastic agents ; Apoptosis ; Cell line ; tumor
• 刊名：Journal of Traditional Chinese Medicine
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：36
• 期：4
• 页码：514-521
• 全文大小：1145 K

文摘

To identify the active anti-tumor constituents in the extract from Danshen (Radix Salviae Miltiorrhizae) and investigate the mechanisms underlying the actions.

Methods

First, we introduced a two-step counter-current chromatography to extract the therapeutically active diterpenoid, tanshinone from Danshen (Radix Salviae Miltiorrhizae). The cholecystokinin (CCK-8) method was used to evaluate the inhibitory effect of diterpenoid tanshinone in liver cancer QGY-7703, lung cancer PC9, lung cancer A549, gastric cancer MKN-45, gastric cancer HGC-27, colon cancer HCT116, myeloma cellU266/RPMI8226, and human breast cancer MCF-7 in vitro. Fluorescence staining was used to observe the cytotoxicity ofditerpenoid tanshinone on PC9 cells. The Western blot was used to detect apoptosis-related protein poly ADP-ribose polymerase (PARP), cysteinyl aspartate specific proteinase3/9 (caspase3/9), and cleaved-cysteinyl aspartate specific proteinase3/9 (cleaved-caspase3/9). The endoplasmic reticulum stress-related activating transcription factor 4 (ATF4), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), and phosphorylated jun amino-terminal kinase (p-JNK), and caspase-12 were also analyzed using the Western blot.

Results

Diterpenoid tanshinone inhibited the nine human tumor cell lines, with an IC50 of 4.37–29 μg/mL, with the PC9 and MCF-7 displaying the lowest values. Fluorescence staining showed a lethal effect of diterpenoid tanshinone on PC9 cells. The Western blot showed that the expression of caspase3/9 protein and ATF-4 protein decreased gradually. However, the PARP, cleaved-caspase 3/9 and the expression of p-eIF2 α, P-JNK, and caspase-12 increased gradually, in a dose-dependent fashion.

Conclusion

We successfully introduced a two-step counter-current chromatography method to extract diterpenoid tanshinone, and demonstrated its antitumor activity. Diterpenoid tanshinone can induce apoptosis in nine human cancer cell lines.