Integrated Treatment of Aqueous Extract of Solanum nigrum-Potentiated Cisplatin- and Doxorubicin-Induced Cytotoxicity in Human Hepatocellular Carcinoma Cells - PubMed (original) (raw)

Integrated Treatment of Aqueous Extract of Solanum nigrum-Potentiated Cisplatin- and Doxorubicin-Induced Cytotoxicity in Human Hepatocellular Carcinoma Cells

Chien-Kai Wang et al. Evid Based Complement Alternat Med. 2015.

Abstract

Chemotherapy is the main approach for treating advanced and recurrent hepatocellular carcinoma (HCC), but the clinical performance of chemotherapy is limited by a relatively low response rate, drug resistance, and adverse effects that severely affect the quality of life of patients. The aqueous extract of Solanum nigrum (AE-SN) is a crucial ingredient in some traditional Chinese medicine (TCM) formulas for treating cancer patients and exhibits antitumor effects in human HCC cells. Therefore, this study examined the tumor-suppression efficiency of AE-SN integrated with a standard chemotherapeutic drug, namely, cisplatin or doxorubicin, in human HCC cells, namely, Hep3B and HepJ5. The results suggested that the integrated treatment with AE-SN-potentiated cisplatin and doxorubicin induced cytotoxicity through the cleavage of caspase-7 and accumulation of microtubule-associated protein-1 light chain-3 A/1B II (LC-3 A/B II), which were associated with apoptotic and autophagic cell death, respectively, in both the Hep3B and HepJ5 cells. In conclusion, AE-SN can potentially be used in novel integrated chemotherapy with cisplatin or doxorubicin to treat HCC patients.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Extracted ion chromatography of solamargine. (a) The parent ion of purified solamargine was fragmented into two daughter ions (blue and red peaks). (b) Fragmented ions presented in AE-SN.

Figure 2

Figure 2

AE-SN treatment inhibited Hep3B and HepJ5 cell growth. (a) Hep3B and HepJ5 cells were treated with 0.1 to 2 mg/mL of AE-SN for 48 h, and the cell viability was determined using an MTT assay. The data are presented as the mean ± standard deviation. (b) Hep3B and HepJ5 cells were treated with 1.0 mg/mL of AE-SN for 48 h, and the cell size distribution was determined according to the cell diameter by using a Scepter cell counter. Arrows indicate a cell diameter of 12 _μ_m.

Figure 3

Figure 3

AE-SN-potentiated cisplatin and doxorubicin induced cytotoxicity in Hep3B and HepJ5 cells but had no effect on normal human pulmonary fibroblasts (WI-38 cells). (a–c) Cells were treated with 0 to 20 _μ_M cisplatin and 0, 0.5, or 1.0 mg/mL of AE-SN for 48 h. (d–f) Cells were treated with 0 to 10 _μ_M doxorubicin and 0, 0.5, or 1.0 mg/mL of AE-SN for 48 h. The cell viability was determined using an MTT assay; the data are presented as the mean ± standard deviation.

Figure 4

Figure 4

AE-SN-activated programmed cell death in Hep3B and HepJ5 cells. (a) Hep3B and (b) HepJ5 cells were treated with a control medium for 48 h. (c) Hep3B and (d) HepJ5 cells were treated with 1.0 mg/mL of AE-SN for 48 h. Arrows indicate the morphological changes present in the AE-SN-treated cells (100x magnification).

Figure 5

Figure 5

Activation of selected protein markers in HCC cells treated with AE-SN and either cisplatin or doxorubicin. (a) Cells were treated with a control medium, namely, 5 _μ_M cisplatin or 2 _μ_M doxorubicin with 0 or 1.0 mg/mL of AE-SN for 48 h. The activation of LC-3 A/B and caspase-7 was determined using western blotting analysis. GAPDH served as an internal control. (b) Semiquantitation of the LC-3 A/B II and cleaved caspase-7 in the Hep3B and HepJ5 cells. The data are presented as the mean ± standard deviation. ∗ indicates statistical significance in comparison with the previous group, namely, Con versus AESN (vehicle control versus AE-SN), Cs versus Cs + AESN, and Dx versus Dx + AESN (two-tailed Student's _t_-test, P < 0.05).

Figure 6

Figure 6

Illustration of the integrated-cell-death mechanism activated by AE-SN and either cisplatin or doxorubicin in HCC cells.

References

    1. El-Serag H. B. Hepatocellular carcinoma. New England Journal of Medicine. 2011;365(12):1118–1127. doi: 10.1056/NEJMra1001683. -DOI -PubMed
    1. Wang Z., Li J., Ji Y., An P., Zhang S., Li Z. Traditional herbal medicine: a review of potential of inhibitory hepatocellular carcinoma in basic research and clinical trial. Evidence-Based Complementary and Alternative Medicine. 2013;2013:7. doi: 10.1155/2013/268963.268963 -DOI -PMC -PubMed
    1. Ernst E., Cassileth B. R. The prevalence of complementary/alternative medicine in cancer: a systematic review. Cancer. 1998;83(4):777–782. doi: 10.1002/(sici)1097-0142(19980815)83:4x0003C;777::aid-cncr22x003E;3.0.co;2-o. -DOI -PubMed
    1. Yang G., Li X., Wang L., et al. Traditional chinese medicine in cancer care: a review of case series published in the chinese literature. Evidence-Based Complementary and Alternative Medicine. 2012;2012:8. doi: 10.1155/2012/751046.751046 -DOI -PMC -PubMed
    1. Dai Z. J., Wang X. J., Li Z. F., et al. Scutellaria barbate extract induces apoptosis of hepatoma H22 cells via the mitochondrial pathway involving caspase-3. World Journal of Gastroenterology. 2008;14(48):7321–7328. doi: 10.3748/wjg.14.7321. -DOI -PMC -PubMed

LinkOut - more resources