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Shikonin induces apoptosis in the human gastric cancer cells HGC-27 through mitochondria-mediated pathway.

Hou Y, Xu J, Liu X, Xia X, Li N, Bi X - Pharmacogn Mag (2015 Apr-Jun)

Bottom Line: In addition, shikonin also caused a significant reduction of the protein Survivin, while having little effect on the expression on X-linked inhibitor of apoptosis protein.Taken together, these results showed that the shikonin exhibited its anti-tumor activity against HGC-27 cells through inhibiting cell growth and promoting apoptosis by targeting mitochondrial-related signaling pathway.Our finding may represent a positive step in finding a natural and effective compound that could be important implication for future development of chemotherapeutic and/or chemopreventive agent against GC.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110004, P.R. China.

ABSTRACT

Background: Gastric cancer (GC) is one of the most frequently occurring digestive tract cancers and fewer chemotherapeutic drugs for GC have shown promising results. In this study, we investigated the anti-tumor activity of shikonin, a natural compound isolated from the Chinese plant Lithospermum erythrorhizon, against the human GC cell line HGC-27.

Materials and methods: HGC-27 cells treated with shikonin at a concentration of 30μM or above showed significant growth inhibition compared to control cells. Shikonin-treated cells also underwent apoptosis as detected by flow cytometric analysis and microscopic examination of cellular morphology. Further investigation into the underlying mechanism of apoptosis by western blot showed that the shikonin promoted the activation of poly-(ADP-ribose)-polymerase, caspase-3 and caspase-9 following 24 h or 48 h of treatment time, as well as the activation of caspase-8, but only after 48 h of treatment time. Furthermore, the levels of mitochondrial membrane potential, B-cell lymphoma 2 (Bcl-2) and Bcl-extra large were reduced following shikonin treatment while the level of Bax was increased. In addition, shikonin also caused a significant reduction of the protein Survivin, while having little effect on the expression on X-linked inhibitor of apoptosis protein.

Conclusion: Taken together, these results showed that the shikonin exhibited its anti-tumor activity against HGC-27 cells through inhibiting cell growth and promoting apoptosis by targeting mitochondrial-related signaling pathway. Our finding may represent a positive step in finding a natural and effective compound that could be important implication for future development of chemotherapeutic and/or chemopreventive agent against GC.

No MeSH data available.


Related in: MedlinePlus

Growth inhibition of HGC-27 cells by shikonin. HGC-27 cells were treated with different concentrations (1, 3, 10, 30 or 100 μM) of shikonin for 24 h and 48 h. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cell viability was expressed as a percentage of surviving cells relative to control cells (no treatment). Data are the mean ± SEM of three independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001 compared to control cells
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Figure 2: Growth inhibition of HGC-27 cells by shikonin. HGC-27 cells were treated with different concentrations (1, 3, 10, 30 or 100 μM) of shikonin for 24 h and 48 h. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cell viability was expressed as a percentage of surviving cells relative to control cells (no treatment). Data are the mean ± SEM of three independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001 compared to control cells

Mentions: The effect of shikonin on the growth of HGC-27 cells was investigated by MTT assay. Shikonin inhibited the growth of HGC-27 cells in a concentration-dependent manner [Figure 2]. Compared to control cells, significant inhibition occurred only at 10 μM and above. At 100 μM shikonin (the highest concentration tested), about 85% of growth was inhibited in the case of 24 h and exposure and 90% when the exposure time was increased to 48 h. Much more intense growth inhibition was also obtained at 48 h compared to 24 h when 30 μM shikonin was used (20% vs. 60%). Thus, the anti-growth effect of shikonin against HGC-27 cells also exhibited a time-dependent effect. The IC50 of a 24 h and 48 h time course for HGC-27 cells was 47.70 μM and 25.78 μM, respectively.


Shikonin induces apoptosis in the human gastric cancer cells HGC-27 through mitochondria-mediated pathway.

Hou Y, Xu J, Liu X, Xia X, Li N, Bi X - Pharmacogn Mag (2015 Apr-Jun)

Growth inhibition of HGC-27 cells by shikonin. HGC-27 cells were treated with different concentrations (1, 3, 10, 30 or 100 μM) of shikonin for 24 h and 48 h. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cell viability was expressed as a percentage of surviving cells relative to control cells (no treatment). Data are the mean ± SEM of three independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001 compared to control cells
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4378121&req=5

Figure 2: Growth inhibition of HGC-27 cells by shikonin. HGC-27 cells were treated with different concentrations (1, 3, 10, 30 or 100 μM) of shikonin for 24 h and 48 h. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cell viability was expressed as a percentage of surviving cells relative to control cells (no treatment). Data are the mean ± SEM of three independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001 compared to control cells
Mentions: The effect of shikonin on the growth of HGC-27 cells was investigated by MTT assay. Shikonin inhibited the growth of HGC-27 cells in a concentration-dependent manner [Figure 2]. Compared to control cells, significant inhibition occurred only at 10 μM and above. At 100 μM shikonin (the highest concentration tested), about 85% of growth was inhibited in the case of 24 h and exposure and 90% when the exposure time was increased to 48 h. Much more intense growth inhibition was also obtained at 48 h compared to 24 h when 30 μM shikonin was used (20% vs. 60%). Thus, the anti-growth effect of shikonin against HGC-27 cells also exhibited a time-dependent effect. The IC50 of a 24 h and 48 h time course for HGC-27 cells was 47.70 μM and 25.78 μM, respectively.

Bottom Line: In addition, shikonin also caused a significant reduction of the protein Survivin, while having little effect on the expression on X-linked inhibitor of apoptosis protein.Taken together, these results showed that the shikonin exhibited its anti-tumor activity against HGC-27 cells through inhibiting cell growth and promoting apoptosis by targeting mitochondrial-related signaling pathway.Our finding may represent a positive step in finding a natural and effective compound that could be important implication for future development of chemotherapeutic and/or chemopreventive agent against GC.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110004, P.R. China.

ABSTRACT

Background: Gastric cancer (GC) is one of the most frequently occurring digestive tract cancers and fewer chemotherapeutic drugs for GC have shown promising results. In this study, we investigated the anti-tumor activity of shikonin, a natural compound isolated from the Chinese plant Lithospermum erythrorhizon, against the human GC cell line HGC-27.

Materials and methods: HGC-27 cells treated with shikonin at a concentration of 30μM or above showed significant growth inhibition compared to control cells. Shikonin-treated cells also underwent apoptosis as detected by flow cytometric analysis and microscopic examination of cellular morphology. Further investigation into the underlying mechanism of apoptosis by western blot showed that the shikonin promoted the activation of poly-(ADP-ribose)-polymerase, caspase-3 and caspase-9 following 24 h or 48 h of treatment time, as well as the activation of caspase-8, but only after 48 h of treatment time. Furthermore, the levels of mitochondrial membrane potential, B-cell lymphoma 2 (Bcl-2) and Bcl-extra large were reduced following shikonin treatment while the level of Bax was increased. In addition, shikonin also caused a significant reduction of the protein Survivin, while having little effect on the expression on X-linked inhibitor of apoptosis protein.

Conclusion: Taken together, these results showed that the shikonin exhibited its anti-tumor activity against HGC-27 cells through inhibiting cell growth and promoting apoptosis by targeting mitochondrial-related signaling pathway. Our finding may represent a positive step in finding a natural and effective compound that could be important implication for future development of chemotherapeutic and/or chemopreventive agent against GC.

No MeSH data available.


Related in: MedlinePlus