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

• Journal of Microbiology and Biotechnology
• /
• v.25 no.7
• /
• pp.1036-1046
• /
• 2015

Extracts from Asian medicinal herbs are known to be successful therapeutic agents against cancer. In this study, the effects of three types of herbal extracts on anti-tumor growth were examined. Among the three types of herbal extracts, H9 showed stronger anti-tumor growth effects than H5 and H11 in vivo. To find the molecular mechanism by which H9 inhibited the proliferation of breast cancer cell lines, the levels of apoptotic markers were examined. Proapoptotic markers, including cleaved PARP and cleaved caspases 3 and 9, were increased, whereas the anti-apoptotic marker Bcl-2 was decreased by H9 treatment. Next, the combined effect of H9 with the chemotherapeutic drugs doxorubicin/cyclophosphamide (AC) on tumor growth was examined using 4T1-tumor-bearing mice. The combined treatment of H9 with AC did not show additive or synergetic anti-tumor growth effects. However, when tumor-bearing mice were co-treated with H9 and the targeted anti-tumor drug trastuzumab, a delay in tumor growth was observed. The combined treatment of H9 and trastuzumab caused an increase of natural killer (NK) cells and a decrease of myeloid-derived suppressor cells (MDSC). Taken together, H9 induces the apoptotic death of tumor cells while increasing anti-tumor immune activity through the enhancement of NK activity and diminishment of MDSC.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
• /
• v.9 no.1
• /
• pp.53-63
• /
• 2003

This study was analyzed the effects of blood-activating and stasis-eliminating herbs on anti-tumor and hematogenic metastasis. The metastasis and recurrence of tumor was the basis of yudok(yudu) on remained tumor cell and stagnation of blood, thermotoxo, phlegm, asthenia of healthy enerngy, stagnation of vital energy. Malignant tumor is caused by carcinogen and go through the progress of initiation, promotion, progression, it is closely related with Eohyul$(y{\grave{u}}xi {\breve{e}})$. Symptoms of blood stasis disease are purplish tongue, mass, fixed stabbing pain, ecchymosis of nail, hypodermic petechia, dermal thesaurismosis, melena, ecchymoma, disturbance of circulation. Effects on the therapy of activating blood circulation and congestion are anti-tumor, anti-coagulation, anti-hemolysis, anti-solution, anti-inflammation, anti-infection, control of blood circulations, control of connective tissue metabolism and control of immunity. They can directly kill the cancer cells entering the blood circulation, inhibit the formation of tumor embody and reduce the blood hyperviscosity. It is suggested that these herbs can be used to prevent and treat blood metastasis of cancer under the guidance of syndrome differentiation.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.18
• /
• pp.8119-8126
• /
• 2016

Cancer is a leading cause of death worldwide. Due to the toxic side effects of the commonly used chemotherapeutic drug cyclophosphamide (CTX), the use of herbal medicines with fewer side effects but having potential use as inducing anti-cancer outcomes in situ has become increasingly popular. The present study sought to investigate the effects of a methanolic extract of Bauhinia tomentosa against Dalton's ascites lymphoma (DAL) induced ascites as well as solid tumors in BALB/c mice. Specifically, B. tomentosa extract was administered intraperitonealy (IP) at 10 mg/kg. BW body weight starting just after tumor cell implantation and thereafter for 10 consecutive days. In the ascites tumor model hosts, administration of extract resulted in a 52% increase in the life span. In solid tumor models, co-administration of extract and CTX significantly reduced tumor volume (relative to in untreated hosts) by 73% compared to just by 52% when the extract alone was provided. Co-administration of the extract also mitigated CTX-induced toxicity, including decreases in WBC count, and in bone marrow cellularity and ${\alpha}$-esterase activity. Extract treatment also attenuated any increases in serum levels of $TNF{\alpha}$, iNOS, IL-$1{\beta}$, IL-6, GM-CSF, and VEGF seen in tumor-bearing hosts. This study confirmed that, the potent antitumor activity of B.tomentosa extract may be associated with immune modulatory effects by regulating anti-oxidants and cytokine levels.

• The Journal of Korean Medicine
• /
• v.25 no.2
• /
• pp.98-109
• /
• 2004

Objectives : To evaluate the anti-tumor and synergic effect of Soonkiwhajungtang with doxorubicin. Methods : The inhibitory concentration (IC), $IC_{50}$ and $IC_{90}$ of single use of doxorubicin and Soonkiwhajungtang with their concomitant treatment against MKN-45 (human stomach carcinoma) cell line were observed using MTT (microculture tetrazolium test) assay. In addition, their anti-tumor effects were also observed in xenograft nude mice models against the MKN-45 cell line. Results : Soonkiwhajungtang has only minimal direct anti-tumor effect against MKN-45 cell line but it reduced general depressed signs induced by implantation of the tumor cell lines and increased the total WBC and lymphocyte numbers. Conclusions : It is considered or expected that Soonkiwhajungtang extract reduces the critical toxicity of doxorubicin and has favorable synergic anti-tumor effect when administered concomitantly with doxorubicin.

• The Journal of Korean Medicine
• /
• v.25 no.2
• /
• pp.9-21
• /
• 2004

Objectives : To evaluate the anti-tumor and synergic effect of Bojungikkeehapdaechilki-tang (BJDC) with doxorubicin. Methods : The inhibitory concentration (IC), $IC_{50}{\;}and{\;}IC_{90}$ of single use of doxorubicin and BIDC with their concomitant treatment against Colon-26 (murine rectum carcinoma) cell line were observed using MTT (microculture tetrazolium test) assay. In addition, their anti-tumor effects were also observed in xenograft nude mice models against Colon-26 cell line. Results : BJDC had only minimal direct anti-tumor effect against Colon-26 cell line but it reduced general depressed signs induced by implantation of the tumor cell lines and increased the total WBC and lymphocyte numbers. Conclusions : It is considered or expected that BJDC extract is reducing the critical toxicity of doxorubicin and has favorable synergic anti-tumor effect when administered conconitently with doxorubicin.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.22 no.2
• /
• pp.39-49
• /
• 2009

Objective : Phyllostachyos Folium (PF) has been used to treat patients with febrile disease consuming the body fluids marked by fever with restlessness, thirst etc. In the theory of herbology, PF can clear away heat and promote the production of the body fluids, relieve restlessness. Recently PF is known to have anti-bacterial, anti-oxidantic effects. Methods : The present study was carried out to investigate the effects of PF on solid tumor in mice in terms of immune-potentiating and direct cytotoxic action of PF in vitro and vivo study. The present author investigated thymocyte and splenocyte proliferation to confirm immune-potentiating activity of PF and also investigated tumor/body weight ratio and survival rates in tumor bearing mice. Result : In this study, administration of PF decreased tumor/body weight ratio significantly, and prolonged survival duration compared to non-treated control. In addition, treatment with PF suppressed proliferation rate of Sarcoma 180 (S-180) cells significantly, and elevated proliferation rates of thymocytes isolated from normal mice. These results were co-related with in vivo study. Conclusion : In conclusion, these results suggest that PF is useful to treat patient with solid tumor, because PF has direct toxic action for tumor cell and immune -potentiating action for T cells. Further study will need to elucidate exact mechanisms related in anti-cancer action of PF.

• The Journal of Internal Korean Medicine
• /
• v.25 no.4
• /
• pp.242-251
• /
• 2004

In this piece of research, Prunellae spica is added to Sambonggangyongbaneotang for one group and Trionycis carapax is added to Sambonggangyongbaneotang for the other group. With these two different prescriptions, the degrees of tumor suppression are compared to develop a better prescription. SKH = Sambonggangyongbaneo-tang + Prunellae Spica SKB = Sambonggangyongbaneo-tang + Trionycis Carapax The results were as follows: 1. SKH and SKB demonstrated anti-tumor effects against tumor advancement of S-180 2. SKH and SKB showed on elevation of macrophage for tumor-bearing mice. 3. $100{\mu}g/ml,\;500{\mu}g/ml$ of SKH and $500{\mu}g/ml$ of SKB demonstrated a rise in alkaline phosphates of B-Lymphocyte in the spleen in tumor-bearing mice. Results support a role for both SKH and SKB for anti-tumor effects via endorsement of macrophage and encouragement of B-lymphocyte toward S-180.

• Journal of Ginseng Research
• /
• v.35 no.4
• /
• pp.462-470
• /
• 2011

Myeloid-derived suppressor cells (MDSCs) actively suppress immune cells and have been considered as an impediment to successful cancer immunotherapy. Many approaches have been made to overcome such immunosuppressive factors and to exert effective anti-tumor effects, but the possibility of using medicinal plants for this purpose has been overlooked. Korean red ginseng (KRG) is widely known to possess a variety of pharmacological properties, including immunoboosting and anti-tumor activities. However, little has been done to assess the anti-tumor activity of KRG on MDSCs. Therefore, we examined the effects of KRG on MDSCs in tumor-bearing mice and evaluated immunostimulatory and anti-tumor activities of KRG through MDSC modulation. The data show that intraperitoneal administration of KRG compromises MDSC function and induces T cell proliferation and the secretion of IL-2 and IFN-${\gamma}$, while it does not exhibit direct cytotoxicity on tumor cells and reduced MDSC accumulation. MDSCs isolated from KRG-treated mice also express significantly lower levels of inducible nitric oxide synthase and IL-10 accompanied by a decrease in nitric oxide production compared with control. Taken together, the present study demonstrates that KRG enhances T cell function by inhibiting the immunosuppressive activity of MDSCs and suggests that although KRG alone does not exhibit direct anti-tumor effects, the use of KRG together with conventional chemo- or immunotherapy may provide better outcomes to cancer patients through MDSC modulation.

• Journal of Ginseng Research
• /
• v.46 no.1
• /
• pp.167-174
• /
• 2022

Background: 20(S)-protopanaxadiol (20(S)-PPD), one of the main active metabolites of ginseng, performs a broad spectrum of anti-tumor effects. Our aims are to search out new strategies to enhance anti-tumor effects of natural products, including 20(S)-PPD. In recent years, fasting has been shown to be multi-functional on tumor progression. Here, the effects of fasting combined with 20(S)-PPD on hepatocellular carcinoma growth, apoptosis, migration, invasion and cell cycle were explored. Methods: CCK-8 assay, trypan blue dye exclusion test, imagings photographed by HoloMonitorTM M4, transwell assay and flow cytometry assay were performed for functional analyses on cell proliferation, morphology, migration, invasion, apoptosis, necrosis and cell cycle. The expressions of genes on protein levels were tested by western blot. Tumor-bearing mice were used to evaluate the effects of intermittent fasting combined with 20(S)-PPD. Results: We firstly confirmed that fasting-mimicking increased the anti-proliferation effect of 20(S)-PPD in human HepG2 cells in vitro. In fasting-mimicking culturing medium, the apoptosis and necrosis induced by 20(S)-PPD increased and more cells were arrested at G0-G1 phase. Meanwhile, invasion and migration of cells were decreased by down-regulating the expressions of matrix metalloproteinase (MMP)-2 and MMP-9 in fasting-mimicking medium. Furthermore, the in vivo study confirmed that intermittent fasting enhanced the tumor growth inhibition of 20(S)-PPD in H22 tumor-bearing mice without obvious side effects. Conclusion: Fasting significantly sensitized HCC cells to 20(S)-PPD in vivo and in vitro. These data indicated that dietary restriction can be one of the potential strategies of chinese medicine or its active metabolites against hepatocellular carcinoma.