IFN-β Induces Caspase-Mediated Apoptosis by Disrupting Mitochondria in Human Advanced Stage Colon Cancer Cell Lines

Juang, Shin‐Hun; Wei, Sung‐Jen; Hung, Yi Mei; Hsu, Chiung-Yueh; Yang, Da; Liu, Ko Jiunn; Chen, Wei Shone; Yang, Wei‐Pang

doi:10.1089/107999004323034105

Cited by 35 publications

(30 citation statements)

References 39 publications

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“…Recently, a number of such gene products and inhibitors for growth factors are increasingly tested in clinical trials [26, 27]. IFN-β is a cytokine that robustly induces caspase-mediated apoptosis of cancer cells through activating different pathways such as mitochondrial and Jak-Stat signaling [28, 29]. IFN-β is also a potent inhibitor of proliferation of many cancer cell lines in vitro [30].…”

Section: Discussionmentioning

confidence: 99%

Human umbilical cord matrix-derived stem cells expressing interferon-β gene inhibit breast cancer cells via apoptosis

et al. 2016

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Human umbilical cord mesenchymal stem cells (hUCMSCs) derived from the umbilical cord matrix have been reported to be used as anti-tumor gene carrier for attenuation of tumor growth, which extends the half-life and lowers the unexpected cytotoxicity of the gene in vivo. Interferon-β (IFNβ) is known to possess robust antitumor effects on different types of cancer cell lines in vitro. The present study was aimed to investigate the anti-tumor effect of IFNβ gene-transfected hUCMSCs (IFNβ-hUCMSCs) on breast cancer cells with emphasis on triple negative breast carcinoma. Our findings revealed that the co-culture of IFNβ-hUCMSCs with the human triple negative breast carcinoma cell lines MDA-MB-231 or Hs578T significantly inhibited growth of both carcinoma cells. In addition, the culture medium conditioned by these cells also significantly suppressed the growth and induced apoptosis of both carcinoma cells. Further investigation showed that the suppressed growth and the apoptosis induced by co-culture of IFNβ-hUCMSCs or conditioned medium were abolished by pretreating anti-IFNβ neutralizing antibody. These findings indicate that IFNβ-hUCMSCs triggered cell death of breast carcinoma cells through IFN-β production, thereby induced apoptosis and suppressed tumor cell growth. In conclusion, we demonstrated that IFNβ-hUCMSCs inhibited the growth of breast cancer cells through apoptosis. with potent anti-cancer activity, it represents as an anti-cancer cytotherapeutic modality against breast cancer.

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Section: Discussionmentioning

confidence: 99%

Human umbilical cord matrix-derived stem cells expressing interferon-β gene inhibit breast cancer cells via apoptosis

et al. 2016

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“…Indeed, a number of such gene products and inhibitors for growth factors are in clinical trials [21–23]. It is well known that the cytokine IFN-β induces apoptosis in cancer cells mainly by disrupting mitochondria and activating the caspase cascade [24]. IFN-β is also a potent inhibitor of proliferation of many cancer cell lines in vitro [2, 25].…”

Section: Discussionmentioning

confidence: 99%

Human umbilical cord matrix-derived stem cells expressing interferon-β gene significantly attenuate bronchioloalveolar carcinoma xenografts in SCID mice

et al. 2010

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SummaryMesenchymal stem cells derived from the human umbilical cord matrix (hUCMSCs) have great potential for therapeutic use for multiple diseases. The strategy that uses therapeutic gene-transfected hUCMSCs as cellular vehicles for targeted biologic agent delivery has solved the problem of short half life or excessive toxicity of biological agent(s) in vivo. Interferon-β (IFN-β) has demonstrated a potent anti-tumor effect on many types of cancer cell lines in vitro. The aim of this study was to determine the anti-cancer effect of IFN-β gene-transfected hUCMSCs (IFN-β-hUCMSCs) on cells derived from bronchioloalveolar carcinoma, a subset of lung adenocarcinoma that is difficult to treat. The co-culture of a small number of IFN-β-hUCMSCs with the human bronchioloalveolar carcinoma cell lines H358 or SW1573 significantly inhibited growth of both types of carcinoma cell lines. The culture medium conditioned by these cells also significantly attenuated the growth of both carcinoma cells, but this attenuation was abolished by adding anti-IFN-β antibody. Finally, systemic administration of IFN-β-hUCMSCs through the tail vein markedly attenuated growth of orthotopic H358 bronchioloalveolar carcinoma xenografts in SCID mice by increasing apoptosis. These results clearly indicate that IFN-β-hUCMSCs caused cell death of bronchioloalveolar carcinoma cells through IFN-β production, thereby attenuating tumor growth in vivo. These results indicate that IFN-β-hUCMSCs are a powerful anti-cancer cytotherapeutic tool for bronchioloalveolar carcinoma.

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“…7 IFN-b induces apoptosis in cancer cells mainly by disrupting mitochondria and activation of the caspase cascade. 25 It also is a potent inhibitor of proliferation for many cancer cells in vitro. 18,19 However, it cannot be used effectively as cancer therapy because the maximum tolerated dose is not high enough to attain these effects when given systemically [26][27][28] and it has a short half-life.…”

Section: Discussionmentioning

confidence: 99%

Development of human umbilical cord matrix stem cell-based gene therapy for experimental lung tumors

et al. 2007

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Umbilical cord matrix stem (UCMS) cells are unique stem cells derived from Wharton's jelly, which have been shown to express genes characteristic of primitive stem cells. To test the safety of these cells, human UCMS cells were injected both intravenously and subcutaneously in large numbers into severe combined immunodeficiency (SCID) mice and multiple tissues were examined for evidence of tumor formation. UCMS cells did not form gross or histological teratomas up to 50 days posttransplantation. Next, to evaluate whether UCMS cells could selectively engraft in xenotransplanted tumors, MDA 231 cells were intravenously transplanted into SCID mice, followed by intravenous transplantation of UCMS cells 1 and 2 weeks later. UCMS cells were found near or within lung tumors but not in other tissues. Finally, UCMS cells were engineered to express human interferon beta -designated 'UCMSÀIFN-b'. UCMSÀIFN-b cells were intravenously transplanted at multiple intervals into SCID mice bearing MDA 231 tumors and their effect on tumors was examined. UCMSÀIFN-b cells significantly reduced MDA 231 tumor burden in SCID mouse lungs indicated by wet weight. These results clearly indicate safety and usability of UCMS cells in cancer gene therapy. Thus, UCMS cells can potentially be used for targeted delivery of cancer therapeutics.

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IFN-β Induces Caspase-Mediated Apoptosis by Disrupting Mitochondria in Human Advanced Stage Colon Cancer Cell Lines

Cited by 35 publications

References 39 publications

Human umbilical cord matrix-derived stem cells expressing interferon-β gene inhibit breast cancer cells via apoptosis

Human umbilical cord matrix-derived stem cells expressing interferon-β gene inhibit breast cancer cells via apoptosis

Human umbilical cord matrix-derived stem cells expressing interferon-β gene significantly attenuate bronchioloalveolar carcinoma xenografts in SCID mice

Development of human umbilical cord matrix stem cell-based gene therapy for experimental lung tumors

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