• BMB Reports
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• v.53 no.10
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• pp.512-520
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• 2020

T-cell-based cancer immunotherapies, such as immune checkpoint blockers (ICBs) and chimeric antigen receptor (CAR)-T-cells, have significant anti-tumor effects against certain types of cancer, providing a new paradigm for cancer treatment. However, the activity of tumor infiltrating T-cells (TILs) can be effectively neutralized in the tumor microenvironment (TME) of most solid tumors, rich in various immunosuppressive factors and cells. Therefore, to improve the clinical outcomes of established T-cell-based immunotherapy, adjuvants that can comprehensively relieve multiple immunosuppressive mechanisms of TME are needed. In this regard, recent studies have revealed that metformin has several beneficial effects on anti-tumor immunity. In this mini-review, we understand the immunosuppressive properties of TME and how metformin comprehensively enhances anti-tumor immunity. Finally, we will discuss this old friend's potential as an adjuvant for cancer immunotherapy.

• IMMUNE NETWORK
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• v.5 no.2
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• pp.110-116
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• 2005

Background: As an attempt to develop a strategy to improve the protective immune response to GM-CSF-secreting CT26 (GM-CSF/CT26) tumor vaccine, we have investigated whether the apoptogenic treatment of GM-CSF/CT26 prior to vaccination enhances the induction of anti-tumor immune response in mouse model. Methods: A carcinogeninduced mouse colorectal tumor, CT26 was transfected with GM-CSF gene using a retroviral vector to generate GM-CSF-secreting CT26 (CT26/GM-CSF). The CT26/GM-CSF was treated with ${\gamma}$-irradiation or mitomycin C to induce apoptosis and vaccinated into BALB/c mice. After 7 days, the mice were injected with a lethal dose of challenge live CT26 cells to examine the protective effect of tumor vaccination in vivo. Results: Although both apoptotic and necrotic CT26/GM-CSF vaccines were able to enhance anti-tumor immune response, apoptotic CT26/GM-CSF induced by pretreatment with ${\gamma}$-irradiation (50,000 rads) was the most potent in generating the anti-tumor immunity, and thus 100% of mice vaccinated with the apoptotic cells remained tumor free for more than 60 days after tumor challenge. Conclusion: Apoptogenic pretreatment of GM-CSF-secreting CT26 tumor vaccine by ${\gamma}$-irradiation (50,000 rads) resulted in a significant enhancement in inducing the protective anti-tumor immunity. A rapid induction of apoptosis of CT26/GM-CSF tumor vaccine at the vaccine site might be critical for the enhancement in anti-tumor immune response to tumor vaccine.

• Biomolecules & Therapeutics
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• v.13 no.2
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• pp.113-117
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• 2005

Organosulfur compounds have been shown to exert an anti-cancer activity. In an attempt to develop novel chemopreventive and anti-cancer agents for liver cancer, we synthesized allylthiopyridazine derivatives. We have previously shown that allylthiopyridazine derivatives exert inhibitory effects on proliferation, invasion and migration of SK-Hep-1 hepatocarcinoma cells in vitro. The in vivo anti-tumor effect of 3-methvl-6-allylthiopy-ridazine, named as K6, was also reported. In this study, we further investigated the preclinical anti-cancer efficacy of K6 for hepatocarcinoma using nude mice xenografted with Hep-G2 hepatocellular carcinoma cells. K6(20-100 mg/kg, orally administered everyday for 30 days) markedly decreased the tumor volume of Hep-G2 cell-transplanted nude mice as evidenced by ultrasonographic and plethysmogranhic analyses. The inhibitory effect on tumor volume was lower than that exerted by doxorubicin (2 mg/kg), intravenously injected) which was used as a positive control. This study shows that K6 efficiently suppresses xenograft tumor growth, revealing K6 as apotential anti-cancer agent for suppressing in vivo progression of liver cancer. Given that hepatocarcinoma is among the most prevalent and lethal malignancies and there is no effective treatment to date, our study may contribute to the potential drug development for liver cancer.

• Advances in Traditional Medicine
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• v.7 no.2
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• pp.133-140
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• 2007

Anti-tumor activity of Euphorbia hirta (50 mg/kg and 100 mg/kg) has been evaluated against Ehrlich's ascites carcinoma (EAC) in Swiss albino mice. Intraperitoneal (i.p) administration of Euphorbia hirta was effective in reducing solid tumor mass development induced by EAC cells. It exhibited significant anti-tumor activity in mice, when used at the dose of 100 mg/kg/day i.p., for 14days. The administration of Euphorbia hirta (100 mg/kg/day i.p.) resulted in an increase (P<0.001) of the life span (59.9%) of ascites tumor bearing mice as compared to the control group. After 14 days, on developed tumor masses, Euphorbia hirta administration brought about significant reduction in tumor volume and it reverse the changes in the hematological parameters, responding to tumor inoculation. The results are indicative of the anti-tumor activity of Euphorbia hirta against EAC induced tumor in a dose dependent manner.

• The Journal of Internal Korean Medicine
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• v.25 no.1
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• pp.92-105
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• 2004

In order to evaluate the anti-tumor and synergic effect of BoJungIkKeeHapDaeChilKi-Tang on doxorubicin, the inhibitory concentration(IC), IC50 and IC90 of single use of doxorubicin and BoJungIkKeeHapDaeChilKi-Tang with their concomitant treatment against MKN-45(Human stomach carcinoma) was observed using MTT(Microculture Tetrazolium test) assay. In addition, their anti-tumor effects were also observed in the xenograft nude mice models agianst MKN-45 cell lines. BoJungIkKeeHapDaeChilKi-Tang has only mimic direct anti-tumor effect against to MKN-45 cell lines but they were decreased general depressed signs induced by implantation of tumor cell lines and increased the total WBC and lymphocyte numbers. So, it is considered or expected that BoJungIkKeeHapDaeChilKi-Tang extracts were reduced by the critical toxicity of doxorubicin and shows favorable synergic effect with doxorubicin and BoJungIkKeeHapDaeChilKi-Tang extracts.

• Herbal Formula Science
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• v.12 no.2
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• pp.119-137
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• 2004

In order to evaluate the anti-tumor and synergic effect of Soonkiwhajungtang with doxorubicin, the inhibitory concentration(IC), $IC_{50}\;and\;IC_{90}$ of single use of doxorubicin and Soonkiwhajungtang with their concomitant treatment against Colon-26(Murine Rectum Carcinoma) was observed using MTT(Microculture Tetrazolium test) assay. In addition, their anti-tumor effects were also observed in the xenograft nude mice models agianst to Colon-26 cell lines. Soonkiwhajungtang has only mimic direct anti-tumor effect against to Colon-26 cell lines but they were decreased general depressed signs induced by implantation of tumor cell lines and increased the total WBC and lymphocyte numbers. So, it is considered or expected that Soonkiwhajungtang extracts were reduced the critical toxicity of doxorubicin and shows favorable synergic effect with doxorubidn and Soonkiwhajungtang extracts.

• Herbal Formula Science
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• v.12 no.1
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• pp.131-148
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• 2004

In order to evaluate the anti-tumor and synergic effect of Bojungikkeehapdaechilkitang with doxorubicin, the inhibitory concentration(IC), $IC_{50}\;and\;IC_{90}$ of single use of doxorubicin and Bojungikkeehapdaechilkitang with their concomitant treatment against 3LL(Lewis lung carcinoma) was observed using MTT(Microculture Tetrazolium test) assay. In addition, their anti-tumor effects were also observed in the xenograft nude mice models agianst to 3LL cell lines. Bojungikkeehapdaechilkitang has only mimic direct anti-tumor effect against to 3LL cell lines but they were decreased general depressed signs induced by implantation of tumor cell lines and increased the total WBC and lymphocyte numbers. So, it is considered or expected that Bojungikkeehapdaechilkitang extracts were reduced the critical toxicity of doxorubicin and shows favorable synergic effect with doxorubicin and Bojungikkeehapdaechilkitang extracts.

• Advances in Traditional Medicine
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• v.7 no.5
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• pp.459-465
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• 2008

The present study was undertaken to investigate the effect of in vivo administration of neem oil intra-peritoneally (i.p.) to mice bearing a progressively growing transplantable T cell lymphoma of spontaneous origin, designated as Daltons lymphoma (DL), on the tumor growth. Mice were administered various doses of neem oil mixed in groundnut oil, which was used as a diluting vehicle or for administration to control DL-bearing mice. Administration of neem oil resulted in an acceleration of tumor growth along with a reduction in the survival time of the tumor-bearing host. Neem oil administered DL-bearing mice showed an augmented apoptosis in splenocytes, bone marrow cells and thymocytes along with an inhibition in the anti-tumor functions of tumor-associated macrophages. Thus this study gives an altogether a novel information that neem oil instead of the popular belief of being anti-tumor and immunoaugmentary may in some tumor-bearing conditions, behave in an opposite way leading to an accelarated tumor progression along with a collapse of the host's anti-tumor machinery. These observations will thus have long lasting clinical significance, suggesting caution in use of neem oil for treatment of cancer.

• Journal of Microbiology and Biotechnology
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• v.25 no.9
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• pp.1485-1492
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• 2015

Makgeolli is a traditional wine in Korea and has been traditionally believed to exhibit health benefits. However, the inhibitory effect of dealcoholized makgeolli (MK) on cancer has never been investigated scientifically. In this study, MK exhibited an anti-angiogenic effect by inhibiting tube formation in human umbilical vein endothelial cells, without cytotoxicity. Treatment with MK reduced the proliferation of AGS human gastric adenocarcinoma cells in a dose-dependent manner and increased the sub-G1 population. Next, we evaluated whether MK could induce apoptosis in AGS cells by using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay or Annexin V method. Treatment with MK at 500 and 1,000 μg/ml increased the number of TUNEL-positive AGS cells. Under the same conditions, MK-treated (500 and 1,000 μg/ml) cells showed significant induction of early or late apoptosis, compared with untreated cells (no induction). In addition, MK also induced phosphatase and tensin homolog (PTEN) expression in AGS cells. However, p53 expression in AGS cells was not changed by MK treatment. Furthermore, MK at 500 mg/kg·d reduced the tumor size and volume in AGS tumor xenografts. Taken together, MK may be useful for the prevention of cancer cell growth.

• The Journal of Internal Korean Medicine
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• v.25 no.2
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• pp.183-194
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• 2004

In order to evaluate the anti-tumor and synergic effect of Soonkiwhajungtang with doxorubicin, the inhibitory concentration(IC), IC50 and IC90 of single use of doxorubicin and Soonkiwhajungtang with their concomitant treatment against Colon-26(Murine Rectum Carcinoma) was observed using MTT(Microculture Tetrazolium test) assay. In addition, their anti-tumor effects were also observed in the xenograft nude mice models against 3LL cell lines. Soonkiwhajungtang may only mimic direct anti-tumor effects against 3LL cell lines, but signs of worsening induced by implantation of tumor cell lines generally decreased, while the total WBC and lymphocyte numbers increased. Therefore, experimentation suggests that Soonkiwhajungtang extracts reduced the critical toxicity of doxorubicin, and that Soonkiwhajungtang extracts have favorable synergic effects when combined with doxorubicin.