Recombinant Human Interleukin-24 Suppresses Gastric Carcinoma Cell Growth<i>In Vitro</i>and<i>In Vivo</i>

Su, Yan; Zhang, Haifeng; Xie, Yufeng; Sheng, Wei; Xiang, Jim; Ye, Zhenmin; Chen, Weichang; Yang, Jicheng

doi:10.3109/07357900903095672

Cited by 22 publications

(6 citation statements)

References 31 publications

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“…IL-24 is also known as melanoma differentiation-associated 7 (mda-7) due to its first discovery from human melanoma cells by combined treatment with IFN-β and MEZ (7). Studies have shown that the overproduction of IL-24 selectively inhibited cancer cell growth of diverse origins by inducing apoptosis with minimal toxicity to normal cells both in vitro and in vivo (8)(9)(10)(11)(12)(13)(14). This broad-spectrum antitumor activity of IL-24 is distinct from that of other extensively studied tumor-suppressor genes, and its growth-inhibition properties are independent of the status of p53, pRb, p21 or additional tumor-suppressor genes in cancer cells (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Interleukin-24 inhibits cell migration and invasion in the neuroblastoma cell line SH-SY5Y

et al. 2013

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Neuroblastomas are common pediatric solid tumors with a variable clinical course; approximately 50% of patients present with metastatic disease at diagnosis. The development of metastatic lesions often causes a fatal outcome. Therefore, the prevention of metastases during the early stage of tumor development is critical for the improvement of the prognosis of neuroblastoma patients. We previously observed the suppression of neuroblastoma growth in response to overexpression of interleukin-24 (IL-24) in vitro and in vivo. IL-24 exerts its tumor-suppressive effects by multiple mechanisms, including the balance of Bcl-2 family proteins toward the pro-apoptotic pathway and the activation of the caspase cascade. In this study, we used adenovirus-mediated IL-24 (Ad-IL24) to examine the effect of the ectopic production of IL-24 on cell migration and invasion in human neuroblastoma cells. We found that IL-24 effectively inhibits SH-SY5Y neuroblastoma cell migration and invasion by changing subcellular localization and cellular levels of β-catenin and regulating the levels of proteins associated with cell migration and invasion. Thus, IL-24 should be considered a therapeutic agent that can inhibit primary neuroblastoma growth and that may prevent metastasis.

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Section: Introductionmentioning

confidence: 99%

Interleukin-24 inhibits cell migration and invasion in the neuroblastoma cell line SH-SY5Y

et al. 2013

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“…Bacterially expressed rhIL-24 protein has also been demonstrated to exert cancer-specific killing activity, providing an alternate therapeutic reagent for cancer therapy (16). rhIL-24 protein has been previously demonstrated to exert in vitro and in vivo antitumor effects in lung cancer (21) and gastric cancer (22). In the present study, the antitumor activity of bacteria-and CHO mammalian cell-derived rhIL-24 protein, and pcDNA3-hIL-24 naked plasmid were assessed in the IL-20R1/IL-20R2-expressing MDA-MB-231 human breast cancer cell line in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Prokaryotically and eukaryotically expressed interleukin-24 induces breast cancer growth suppression via activation of apoptosis and inhibition of tumor angiogenesis

Wei

Cao

Zhou

et al. 2014

Molecular Medicine Reports

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Melanoma differentiation‑associated‑7 (mda‑7)/interleukin‑24 (IL‑24), a unique cytokine‑tumor suppressor, exerts tumor‑selective killing activity in numerous types of cancer cell. Although eukaryotically and prokaryotically expressed recombinant human (rh)IL‑24 proteins have been previously shown to produce potent antitumor effects, to the best of our knowledge, no side‑by‑side study has been conducted that compares the two proteins directly. In the present study, rhIL‑24 protein was expressed in BL21 Escherichia coli transformed with the pET‑21a(+)‑hIL‑24 plasmid by isopropyl‑β‑D‑1‑thiogalactopyranoside induction. Following a denaturing and renaturing process, the soluble rhIL‑24 was purified using a Q‑Sepharose column. rhIL‑24 protein was also expressed in Chinese hamster ovary mammalian cells stably transfected with the pcDNA3‑hIL‑24 plasmid. The in vitro antitumor efficacies of the two treatments were compared using the MDA‑MB‑231 human breast cancer cell line. Furthermore, the therapeutic efficacies of the bacteria‑derived rhIL‑24 protein and the liposome‑coated pcDNA3‑hIL‑24 naked plasmid were evaluated in athymic nude mice with subcutaneously xenografted MDA‑MB‑231 cell tumors. The prokaryotically expressed/purified rhIL‑24 protein and the eukaryotically expressed rhIL‑24 in the cell supernate were revealed to be capable of efficiently suppressing MDA‑MB‑231 tumor growth in vitro. Similarly, the administration of bacteria‑derived rhIL‑24 protein and pcDNA3‑hIL‑24 naked plasmid also provided therapeutic benefits in the treatment of in vivo MDA‑MB‑231 xenografted tumors. The retarded in vitro and in vivo breast cancer growth elicited by rhIL‑24 was closely associated with the upregulation of the ratio of anti‑apoptotic B cell lymphoma 2 (Bcl‑2) to pro‑apoptotic Bcl‑2‑associated X protein (Bax), as well as the activation of caspase‑3 followed by marked induction of apoptosis, and the notable inhibition of tumor angiogenesis. Thus, the results of the present study indicate that prokaryotically expressed rhIL‑24 protein may be an alternate and promising antitumor agent in human breast cancer or other types of cancer.

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“…rmhTNF-α and RGD-rmhTNF-α were prepared by recombinant DNA technology and were purified from Escherichia coli cell extracts as previously described [20], [21]. rmhTNF-α and RGD-rmhTNF-α were purified to 97.5% and 95% purity, respectively, by high-performance liquid chromatography.…”

Section: Methodsmentioning

confidence: 99%

Tumor Vasculature-Targeted Recombinant Mutated Human TNF-α Enhanced the Antitumor Activity of Doxorubicin by Increasing Tumor Vessel Permeability in Mouse Xenograft Models

Jiang

Niu

et al. 2014

PLoS ONE

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ObjectiveIncreasing evidence suggests that, when used in combination, tumor necrosis factor-α (TNF-α) synergizes with traditional chemotherapeutic drugs to exert a heightened antitumor effect. The present study investigated the antitumor efficacy of recombinant mutated human TNF-α specifically targeted to the tumor vasculature (RGD-rmhTNF-α) combined with the chemotherapeutic agent doxorubicin in 2 murine allografted tumor models.MethodsMice bearing hepatoma or sarcoma allografted tumors were treated with various doses of RGD-rmhTNF-α alone or in combination with doxorubicin (2 mg/kg). We then evaluated tumor growth and tumor vessel permeability as well as intratumoral levels of RGD-rmhTNF-α and doxorubicin.ResultsRGD-rmhTNF-α treatment enhanced the permeability of the tumor vessels and increased intratumoral doxorubicin levels. In addition, intratumoral RGD-rmhTNF-α levels were significantly higher than that of rmhTNF-α. In both of the tested tumor models, administering RGD-rmhTNF-α in combination with doxorubicin resulted in an enhanced antitumor response compared to either treatment alone. Double-agent combination treatment of doxorubicin with 50,000 IU/kg RGD-rmhTNF-α induced stronger antitumor effects on H22 allografted tumor-bearing mice than the single doxorubicin agent alone. Moreover, doxorubicin with 10,000 IU/kg RGD-rmhTNF-α synergized to inhibit tumor growth in S180 allografted tumor-bearing mice.ConclusionsThese results suggest that targeted delivery of low doses of RGD-rmhTNF-α into the tumor vasculature increases the antitumor efficacy of chemotherapeutic drugs.

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Recombinant Human Interleukin-24 Suppresses Gastric Carcinoma Cell GrowthIn VitroandIn Vivo

Cited by 22 publications

References 31 publications

Interleukin-24 inhibits cell migration and invasion in the neuroblastoma cell line SH-SY5Y

Interleukin-24 inhibits cell migration and invasion in the neuroblastoma cell line SH-SY5Y

Prokaryotically and eukaryotically expressed interleukin-24 induces breast cancer growth suppression via activation of apoptosis and inhibition of tumor angiogenesis

Tumor Vasculature-Targeted Recombinant Mutated Human TNF-α Enhanced the Antitumor Activity of Doxorubicin by Increasing Tumor Vessel Permeability in Mouse Xenograft Models

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