Shikonin, a Chinese plant-derived naphthoquinone, induces apoptosis in hepatocellular carcinoma cells through reactive oxygen species: A potential new treatment for hepatocellular carcinoma

Gong, Kan; Li, Wenhua

doi:10.1016/j.freeradbiomed.2011.09.018

Cited by 129 publications

(97 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Shikonin, a natural naphthoquinone isolated from the herb Lithospermum erythrorhizon, has been found to inhibit tumor growth and induce cell cycle arrest and apoptosis of various cancer cells, including HCC, through reactive oxygen species (Gong and Li, 2011). Our data presented here show that shikonin also has the ability to enhance rAAV vector-mediated transgene expression through its proteasome inhibitor activity.…”

Section: Discussionmentioning

confidence: 59%

“…It is worth noticing that most natural drugs are multifunctional (Ling et al, 2014b) and therefore have the potential to play an additive, even synergistic, effect on rAAV vector-based cancer gene therapy. For instance, shikonin, a major component of Lithospermum erythrorhizon, was reported to have various biological activities, including proteasome inhibitor activity (Yang et al, 2009), as well as activities to induce apoptosis in HCC cells through reactive oxygen species (Gong and Li, 2011).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

SelectiveIn VivoTargeting of Human Liver Tumors by Optimized AAV3 Vectors in a Murine Xenograft Model

et al. 2014

View full text Add to dashboard Cite

Current challenges for recombinant adeno-associated virus (rAAV) vector-based cancer treatment include the low efficiency and the lack of specificity in vivo. rAAV serotype 3 (rAAV3) vectors have previously been shown to be ineffective in normal mouse tissues following systemic administration. In the present study, we report that rAAV3 vectors can efficiently target and transduce various human liver cancer cells in vivo. Elimination of specific surface-exposed serine and threonine residues on rAAV3 capsids results in further augmentation in the transduction efficiency of these vectors, without any change in the viral tropism and cellular receptor interactions. In addition, we have identified a potential chemotherapy drug, shikonin, as a multifunctional compound to inhibit liver tumor growth as well as to significantly enhance the efficacy of rAAV vector-based gene therapy in vivo. Furthermore, we also document that suppression of tumorigenesis in a human liver cancer xenograft model can be achieved through systemic administration of the optimized rAAV3 vectors carrying a therapeutic gene, and shikonin at a dose that does not lead to liver damage. Our research provides a novel means to achieve not only targeted delivery but also the potential for gene therapy of human liver cancer.

show abstract

Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

SelectiveIn VivoTargeting of Human Liver Tumors by Optimized AAV3 Vectors in a Murine Xenograft Model

et al. 2014

View full text Add to dashboard Cite

show abstract

“…HCC is responsible for ~600,000 deaths annually worldwide (1,2). This is related to various biological predisposing factors such as hepatitis B, hepatitis C and liver cirrhosis, all of which can progress into hepatocellular carcinoma (3).…”

Section: Bioactive Chemical Constituents Of Curcuma Longa L Rhizomesmentioning

confidence: 99%

Bioactive chemical constituents of Curcuma longa L. rhizomes extract inhibit the growth of human hepatoma cell line (HepG2)

et al. 2016

View full text Add to dashboard Cite

The present study was designed to identify the chemical constituents of the methanolic extract of Curcuma longa L. rhizomes and their inhibitory effect on a hepatoma cell line. The methanolic extract was subjected to GC-MS analysis to identify the volatile constituents and the other part of the same extract was subjected to liquid column chromatographic separation to isolate curcumin. The inhibition of cell growth in the hepatoma cell line and the cytopathological changes were studied. GC-MS analysis showed the presence of fifty compounds in the methanolic extract of C. longa. The major compounds were ar-turmerone (20.50 %), β-sesquiphellandrene (5.20 %) and curcumenol (5.11 %). Curcumin was identified using IR, 1H and 13C NMR. The inhibition of cell growth by curcumin (IC50 = 41.69 ± 2.87 μg mL-1) was much more effective than that of methanolic extract (IC50 = 196.12 ± 5.25 μg mL-1). Degenerative and apoptotic changes were more evident in curcumin- treated hepatoma cells than in those treated with the methanol extract. Antitumor potential of the methanolic extract may be attributed to the presence of sesquiterpenes and phenolic constituents including curcumin (0.051 %, 511.39 μg g-1 dried methanol extract) in C. longa rhizomes.

show abstract

“…Many studies showed that some chemotherapeutic agents activated intracellular ROS accumulation and subsequently induced apoptosis in certain types of cancer cells (Loor et al, 2010;Gong and Li, 2011). The excessive production of ROS often leads to mitochondrial depolarization.…”

Section: Ros Generation and Mitochondrial Depolarization Are Involvedmentioning

confidence: 99%

ABT‐263 enhances sorafenib‐induced apoptosis associated with Akt activity and the expression of Bax and p21⁽^CIP1/WAF1⁾ in human cancer cells

Chen

Wan

et al. 2014

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

BACKGROUND AND PURPOSESorafenib, a potent inhibitor that targets several kinases associated with tumourigenesis and cell survival, has been approved for clinical treatment as a single agent. However, combining sorafenib with other agents improves its anti-tumour efficacy in various preclinical tumour models. ABT-263, a second-generation BH3 mimic, binds to the anti-apoptotic family members Bcl-2, Bcl-xL and Bcl-w, and has been demonstrated to enhance TNFSF10 (TRAIL)-induced apoptosis in human hepatocarcinoma cells. Hence, we investigated the effects of ABT-263 treatment combined with sorafenib. EXPERIMENTAL APPROACHThe effects of ABT-263 combined with sorafenib were investigated in vitro, on cell viability, clone formation and apoptosis, and the mechanism examined using western blot and flow cytometry. This combination was also evaluated in vivo, in a mouse xenograft model; tumour growth, volume and weights were measured and a TUNEL assay performed. KEY RESULTSABT-263 enhanced sorafenib-induced apoptosis while sparing non-tumourigenic cells. Although ABT-263 plus sorafenib significantly stimulated intracellular reactive oxygen species production and subsequent mitochondrial depolarization, this was not sufficient to trigger cell apoptosis. ABT-263 plus sorafenib significantly decreased Akt activity, which was, at least partly, involved in its effect on apoptosis. Bax and p21 (CIP1/WAF1) were shown to play a critical role in ABT-263 plus sorafenib-induced apoptosis. Combining sorafenib with ABT-263 dramatically increased its efficacy in vivo. CONCLUSION AND IMPLICATIONSThe anti-tumour activity of ABT-263 plus sorafenib may involve the induction of intrinsic cell apoptosis via inhibition of Akt, and reduced Bax and p21 expression. Our findings offer a novel effective therapeutic strategy for tumour treatment. AbbreviationsΔΨm, mitochondrial membrane potential; CsA, cyclosporine A; NAC, N-acetyl-L-cysteine; PI, propidium iodide; ROS, reactive oxygen species BJP British Journal of Pharmacology

show abstract

Shikonin, a Chinese plant-derived naphthoquinone, induces apoptosis in hepatocellular carcinoma cells through reactive oxygen species: A potential new treatment for hepatocellular carcinoma

Cited by 129 publications

References 45 publications

SelectiveIn VivoTargeting of Human Liver Tumors by Optimized AAV3 Vectors in a Murine Xenograft Model

SelectiveIn VivoTargeting of Human Liver Tumors by Optimized AAV3 Vectors in a Murine Xenograft Model

Bioactive chemical constituents of Curcuma longa L. rhizomes extract inhibit the growth of human hepatoma cell line (HepG2)

ABT‐263 enhances sorafenib‐induced apoptosis associated with Akt activity and the expression of Bax and p21⁽^CIP1/WAF1⁾ in human cancer cells

Contact Info

Product

Resources

About

Shikonin, a Chinese plant-derived naphthoquinone, induces apoptosis in hepatocellular carcinoma cells through reactive oxygen species: A potential new treatment for hepatocellular carcinoma

Cited by 129 publications

References 45 publications

SelectiveIn VivoTargeting of Human Liver Tumors by Optimized AAV3 Vectors in a Murine Xenograft Model

SelectiveIn VivoTargeting of Human Liver Tumors by Optimized AAV3 Vectors in a Murine Xenograft Model

Bioactive chemical constituents of Curcuma longa L. rhizomes extract inhibit the growth of human hepatoma cell line (HepG2)

ABT‐263 enhances sorafenib‐induced apoptosis associated with Akt activity and the expression of Bax and p21(CIP1/WAF1) in human cancer cells

Contact Info

Product

Resources

About

ABT‐263 enhances sorafenib‐induced apoptosis associated with Akt activity and the expression of Bax and p21⁽^CIP1/WAF1⁾ in human cancer cells