Cytotoxic effects induced by interferon-ω gene lipofection through ROS generation and mitochondrial membrane potential disruption in feline mammary carcinoma cells

Villaverde, Marcela Solange; Targovnik, Alexandra Marisa; Miranda, Magdalena; Finocchiaro, Liliana M.E.; Glikin, Gerardo C.

doi:10.1016/j.cyto.2016.05.018

Cited by 8 publications

(19 citation statements)

References 31 publications

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“…Accumulation of intracellular ROS typically depolarizes mitochondrial membrane potential (MMP)45. Thus, we detected the MMP of SGC-7901 gastric cancer cells after treatment of SHK.…”

Section: Resultsmentioning

confidence: 97%

Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species

Liang

Cai

Chen³

et al. 2016

Sci Rep

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The prognosis of gastric cancer remains poor due to clinical drug resistance. Novel drugs are urgently needed. Shikonin (SHK), a natural naphthoquinone, has been reported to trigger cell death and overcome drug resistance in anti-tumour therapy. In this study, we investigated the effectiveness and molecular mechanisms of SHK in treatment with gastric cancer. In vitro, SHK suppresses proliferation and triggers cell death of gastric cancer cells but leads minor damage to gastric epithelial cells. SHK induces the generation of intracellular reactive oxygen species (ROS), depolarizes the mitochondrial membrane potential (MMP) and ultimately triggers mitochondria-mediated apoptosis. We confirmed that SHK induces apoptosis of gastric cancer cells not only in a caspase-dependent manner which releases Cytochrome C and triggers the caspase cascade, but also in a caspase-independent manner which mediates the nuclear translocation of apoptosis-inducing factor and Endonuclease G. Furthermore, we demonstrated that SHK enhanced the chemotherapeutic sensitivity of 5-fluorouracil and oxaliplatin in vitro and in vivo. Taken together, our data show that SHK may be a novel therapeutic agent in the clinical treatment of gastric cancer.

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“…Accumulation of intracellular ROS typically depolarizes mitochondrial membrane potential (MMP)45. Thus, we detected the MMP of SGC-7901 gastric cancer cells after treatment of SHK.…”

Section: Resultsmentioning

confidence: 97%

Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species

Liang

Cai

Chen³

et al. 2016

Sci Rep

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“…The accumulation of intracellular ROS could be generated not only by abnormal metabolism but also by exogenous sources of drugs. ROS contain reactive chemical oxygen that could activate mitochondria-dependent apoptosis [ 28 – 30 ]. Previous studies have reported that shikonin induces the accumulation of ROS in some tumor cells [ 12 , 31 ].…”

Section: Resultsmentioning

confidence: 99%

Shikonin induces ROS-based mitochondria-mediated apoptosis in colon cancer

et al. 2017

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Colon cancer is the third most common malignancy worldwide, and chemotherapy is a widely used strategy in clinical therapy. Chemotherapy-resistant of colon cancer is the main cause of recurrence and progression. Novel drugs with efficacy and safety in treating colon cancer are urgently needed. Shikonin, a naphthoquinone derived from the roots of the herbal plant Lithospermum erythrorhizon, has been determined to be a potent anti-tumor agent. The aim of the present study was to detect the underlying anti-tumor mechanism of shikonin in colon cancer. We found that shikonin suppressed the growth of colon cancer cells in a dose-dependent manner in vitro and in vivo. Shikonin induced mitochondria-mediated apoptosis, which was regulated by Bcl-2 family proteins. Shikonin increased the generation of intracellular ROS, which played an upstream role in shikonin-induced apoptosis. Our data indicated that generation of ROS, down-regulated expression of Bcl-2 and Bcl-xL, depolarization of the mitochondrial membrane potential and activation of the caspase cascade were components of the programmed event of shikonin-induced apoptosis in colon cancer cells. In addition, shikonin presented minimal toxicity to non-neoplastic colon cells and no liver injury in xenograft models, showing safety in the control of colon cancer cell growth in vitro and in vivo. Taken together, our findings suggest that shikonin might serve as a potential novel therapeutic drug in the treatment of human colon cancer.

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“…apoptosis, necrosis, and early senescence) of human IFNβ gene lipofection showed the same or a superior effect to that of high doses of the exogenously applied recombinant IFNβ protein [76]. Based on these findings, the researchers also found that fIFN-ω lipofection and expression is equal to or more effective than rFIFN-ω protein at suppressing cell growth by inducing ROS generation, mitochondrial potential disruption and calcium uptake [77]. These kinds of approaches may offer equal or superior biological activities with less adverse effects for the treatment of some diseases.…”

Section: Biological Activities Of Type I Ifnsmentioning

confidence: 97%

Type I Interferons: Distinct Biological Activities and Current Applications for Viral Infection

Gong

Zhao

et al. 2018

Cell Physiol Biochem

141

116

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The interferons (IFNs) are a primary defense against pathogens because of the strong antiviral activities they induce. IFNs can be classified into three groups: type I, type II and type III, according to their genetic, structural, and functional characteristics and their receptors on the cell surface. The type I IFNs are the largest group and include IFN-α, IFN-β, IFN-ε, IFN-ω, IFN-κ, IFN-δ, IFN-τ and IFN-ζ. The use of IFNs for the treatment of viral infectious diseases on their antiviral activity may become an important therapeutic option, for example, IFN-α is well known for the successful treatment of hepatitis B and C virus infections, and interest is increasing in the antiviral efficacy of other novel IFN classes and their potential applications. Therefore, in this review, we summarize the recent progress in the study of the biological activities of all the type I IFN classes and their potential applications in the treatment of infections with immunodeficiency virus, hepatitis viruses, and influenza viruses.

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Cytotoxic effects induced by interferon-ω gene lipofection through ROS generation and mitochondrial membrane potential disruption in feline mammary carcinoma cells

Cited by 8 publications

References 31 publications

Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species

Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species

Shikonin induces ROS-based mitochondria-mediated apoptosis in colon cancer

Type I Interferons: Distinct Biological Activities and Current Applications for Viral Infection

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