• Journal of Ginseng Research
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• v.47 no.2
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• pp.173-182
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• 2023

Cancer is a global public health issue that becomes the second primary cause of death globally. Considering the side effects of radio- or chemo-therapy, natural phytochemicals are promising alternatives for therapeutic interventions to alleviate the side effects and complications. Ginsenoside Rh2 (GRh2) is the main phytochemical extracted from Panax ginseng C.A. Meyer with anticancer activity. GRh2 could induce apoptosis and autophagy of cancer cells and inhibit proliferation, metastasis, invasion, and angiogenesis in vitro and in vivo. In addition, GRh2 could be used as an adjuvant to chemotherapeutics to enhance the anticancer effect and reverse the adverse effects. Here we summarized the understanding of the molecular mechanisms underlying the anticancer effects of GRh2 and proposed future directions to promote the development and application of GRh2.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2599-2605
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• 2013

The study aimed to evaluate immune-stimulating effects of a well-known Thai folkloric remedy when used for adjuvant therapy with conventional chemotherapeutics for treatment of breast cancer. Immunostimulating influence of the remedy (215 mg/kg body weight per day) on NK cell activity and TNF-${\alpha}$ release from the monocytes/macrophages were investigated in a total of 15 healthy women and 13 female patients with breast cancer (Group 1). The effect of breast tumor surgery on NK cell activity was further investigated in 18 female patients with breast cancer (Group 2). NK cell cytotoxic activity was determined by chromium release cytotoxic assay using K562, an erythroleukemic cell line. TNF-${\alpha}$ release from monocytes/macrophages separated from blood samples was determined through a biological assay using actinomycin D-treated L929 mouse fibroblast cells in the presence and absence of LPS. Baseline NK cell activity of the monocytes/macrophages separated from Group 2 patients expressed as %cytotoxicity was significantly lower than in the healthy subjects at E:T ratios of 100:1 and 25:1. In healthy subjects, there was no change in NK cell cytotoxic activity (%cytotoxicity or LU) following 1 and 2 weeks of treatment with the remedy compared with the baseline at various E:T ratios but the binding activity (%binding) was significantly increased after 2 weeks of treatment. The addition of one or two conventional chemotherapeutic regimens did not significantly reduce the NK cytotoxic activity but did affect release of TNF-${\alpha}$ in both unstimulated and LPS-stimulated samples. Surgery produced a significant suppressive effect on NK cell activity. The use of the remedy as an adjunct therapy may improve therapeutic efficacy and safety profiles of conventional chemotherapeutic regimens through stimulation of the immune system in cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5785-5790
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• 2012

The use of chemotherapeutics induces cardiotoxicity and affects immune functions, therefore development of combinatorial agents against cardiotoxicity and immunosuppression needs to be explored. Previous studies of the hexane insoluble fraction (HIF) of an ethanolic extract of Ficus septica leaves showed anticancer effects singly and in combination with doxorubicin on T47D breast cancer cells. In this present study, it was evaluated for its immunomodulatory activities in doxorubicin-treated rats. Thirty male Sprague Dawley rats were divided into five groups consisting of six rats each as follows: Group 1, receiving oral saline 10 ml/kg BW (control group); Group 2, receiving HIF dose 750 mg/kg BW orally, once daily; Group 3, receiving HIF dose 1.500 mg/kg BW orally, once daily; Group 4, given oral saline 10 ml/kg BW (normal group); Group 5, receiving HIF dose 1.500 mg/kg BW orally, once daily. The rats of group 1-3 were intramuscularly administered with doxorubicin at a dose of 4.67 mg/kg BW at the days 1 and 4 to suppress immune functions. Concomitantly, the rats were treated with saline or HIF for seven consecutive days (1 to 7). Treatment of HIF succeeded in reducing side effects of doxorubicin based on increasing lymphocyte density and phagocytosis activity and capacity of macrophages, as well as increasing the CD8+ blood level and decreasing spleen IL-10 expression. Hexane insoluble fraction of of ethanolic extract of Ficus septica leaves has potential as a protective agent combined with doxorubicin.

• Journal of the Korean Society of Food Science and Nutrition
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• v.23 no.6
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• pp.922-926
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• 1994

This study was carried out to detemrine the efficacy of combined treatment of cyclophosphamide with tubericin-3 and or picibanil. One hundred sixty sarcoma-180 bearing mice were divided eight groups. Each group received saline, tubercin-3, picibanil , and cyclophosphamide along and/or received cyclophosphamide with tubercin-3 , with picibanil or with both tubercin-3 and picinanil, respectively.Average surviving time of each group of animals was as follows ; control was 10.9days, tubercin-3 was 15.1 days. picibanil was 12.6 days, and cylophosphamide was 17.9 days, In combined therapyy that cylophosphamide injected with tubercin-3 , the surviving time was 26.8 days an din the case of other therapy that cyclophosphamide injected with tubercin-3, the surviving time was 26.8 days an din the case of other therapy that cyclophosphamide injected with picibanil, the surviving time was 21.9 day and cyclophosphamide treated with both turbercin03 and picibanil, the surviving time was found to be 18.2 days, conclusively , the therapeutic potentiation seemed to be extended when combined tretment of the chemotherapeutics cyclophosphamide with either one of immunotherapeutics tubericin-3 or picibanil was tried, Combinatin of tubercin-3 and picibanil showed to be atagonistic each other. Yield of ascites fluid were determined 7 days after injectino of sarcoma-180 ascites tumor cells. Adminitration of cyclophosphamide, tubercin-3 , and picibanil alone and their various combinations reduced the yield of ascites fluid except for picibanil group.

• Parasites, Hosts and Diseases
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• v.31 no.3
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• pp.277-284
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• 1993

Leishmaniasis is one of the important tropical diseases in the world. Although it is not prevalent In Korea, imported cases have been recorded. The karyotype of Leishmcnic sp. has been observed to be variable by localities or by strains, but the karyotype of a strain is known to be stable. This study was performed to observe if the karyotype of a Leishmonio sp. would be changed under some stressful conditions. The karyotype, analyzed by pulsed Held gradient gel electrophoresis, was not grossly changed by heat shock, chemotherapeutics, UV illumination, and gamma irradiation. Radiation destroyed the chromosomes mechanically but subcultured organisms after irradiation showed unaffected karyotype. The present findings suggest that the karyotype of a Leishmnnia strain is so stable that it is not altered by temporary stimulation with heat, drugs, and radiation.

• Biomolecules & Therapeutics
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• v.11 no.2
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• pp.85-90
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• 2003

Microtubule-binding molecules have been developed as anti-cancer agents to overcome the toxicities of current chemotherapeutics and also have potential for use as anti-angiogenic agents. In this work, we examined the effect of novel triazine compounds, Tubulyzines (microTUBUle LYsing triaZINE), derived from the orthogonal synthesis of a triazine library, on endothelial progenitor cell differentiation. When mononuclear cells isolated from human cord blood were cultured on fibronectin-coated plates for 7 days, all the Tubulyzine compounds A, B, and C (TA, TB, and TC) tested decreased the number of adherent cells in a dose-dependent manner in a coo. centration ranges of 2-5 to $80\mu\textrm{M}$. TA ($IC_{50}$=$20\mu\textrm{M}$) showed slightly more potent activity than TB and TC. Adherent cells treated with TA also exhibited a lower level of ability to ac-LDL uptake, with low ratios of positive cells out of total adherent cells, in a dose-dependent manner and weak expression of endothelial lineage markers, KDR, CD31, and vWF at $20\mu\textrm{M}$. Therefore, these results suggest that tubulyzine A (TA) can be effectively used for the inhibition of new vessel growth by inhibiting differentiation of endothelial progenitor cells.

• Biomolecules & Therapeutics
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• v.22 no.2
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• pp.114-121
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• 2014

Refractoriness of acute myeloid leukemia (AML) cells to chemotherapeutics represents a major clinical barrier. Suicide gene therapy for cancer has been attractive but with limited clinical efficacy. In this study, we investigated the potential application of herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) based system to inhibit chemoresistant AML cells. We first generated Ara-C resistant K562 cells and doxorubicin-resistant THP-1 cells. We found that the HSV-TK/GCV anticancer system suppressed drug resistant leukemic cells in culture. Chemoresistant AML cell lines displayed similar sensitivity to HSV-TK/GCV. Moreover, HSV-TK/GCV killing of leukemic cells was augmented to a mild but significant extent by all-trans retinoic acid (ATRA) with concomitant upregulation of Connexin 43, a major component of gap junctions. Interestingly, HSV-TK/GCV killing was enhanced by expression of vesicular stomatitis virus G glycoprotein (VSV-G), a fusogenic membrane protein, which also increased leukemic cell fusion. Co-culture resistant cells expressing HSV-TK and cells stably transduced with VSV-G showed that expression of VSV-G could promote the bystander killing effect of HSV-TK/GCV. Furthermore, combination of HSV-TK/GCV with VSV-G plus ATRA produced more pronounced antileukemia effect. These results suggest that the HSV-TK/GCV system in combination with fusogenic membrane proteins and/or ATRA could provide a strategy to mitigate the chemoresistance of AML.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2739-2744
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• 2012

Background: Renal-cell carcinoma (RCC) is resistant to almost all chemotherapeutics and radiation therapy. ${\beta}$-Elemene, a promising anticancer drug extracted from a traditional Chinese medicine, has been shown to be effective against various tumors. In the present study, anti-tumor effects on RCC cells and the involved mechanisms were investigated. Methods: Human RCC 786-0 cells were treated with different concentrations of ${\beta}$-elemene, and cell viability and apoptosis were measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry, respectively. Protein expression was assayed by western blotting. Autophagy was evaluated by transmission electron microscopy. Results: ${\beta}$-Elemene inhibited the viability of 786-0 cells in a dose- and time-dependent manner. The anti-tumor effect was associated with induction of apoptosis. Further study showed that ${\beta}$-elemene inhibited the MAPK/ERK as well as PI3K/Akt/mTOR signalling pathways. Moreover, robust autophagy was observed in cells treated with ${\beta}$-elemene. Combined treatment of ${\beta}$-elemene with autophagy inhibitors 3-methyladenine or chlorochine significantly enhanced the anti-tumor effects. Conclusions: Our data provide first evidence that ${\beta}$-elemene can inhibit the proliferation of RCC 786-0 cells by inducing apoptosis as well as protective autophagy. The anti-tumor effect was associated with the inhibition of MAPK/ERK and PI3K/Akt/mTOR signalling pathway. Inhibition of autophagy might be a useful way to enhance the anti-tumor effect of ${\beta}$-elemene on 786-0 cells.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2911-2916
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• 2014

Oxaliplatin is a first-line therapy for colorectal cancer, but cancer cell resistance to the drug compromises its efficacy. To explore mechanisms of drug resistance, we treated colorectal cancer cells (HCT116 and SW620) long-term with oxaliplatin and established stable oxaliplatin-resistant lines (HCT116-OX and SW620-OX). Compared with parental cell lines, $IC_{50}$s for various chemotherapeutic agents (oxaliplatin, cisplatin and doxorubicin) were increased in oxaliplatin-resistant cell lines and this was accompanied by activation of nuclear factor erythroid-2 p45-related factor 2 (Nrf2) and NADPH quinone oxidoreductase 1 (NQO1). Furthermore, luteolin inhibited the Nrf2 pathway in oxaliplatin-resistant cell lines in a dose-dependent manner. Luteolin also inhibited Nrf2 target gene [NQO1, heme oxygenase-1 (HO-1) and $GST{\alpha}1/2$] expression and decreased reduced glutathione in wild type mouse small intestinal cells. There was no apparent effect in Nrf2-/- mice. Luteolin combined with other chemotherapeutics had greater anti-cancer activity in resistant cell lines (combined index values below 1), indicating a synergistic effect. Therefore, adaptive activation of Nrf2 may contribute to the development of acquired drug-resistance and luteolin could restore sensitivity of oxaliplatin-resistant cell lines to chemotherapeutic drugs. Inhibition of the Nrf2 pathway may be the mechanism for this restored therapeutic response.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4659-4664
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• 2015

Background: ABC proteins are one key type of transport superfamilies which undertake majority of drug transport, which affect the osteosarcoma response to chemotherapeutics. Previous studies have suggested the association between ABC polymorphisms and osteosarcoma response. However, the results of previous studies remain controversial. Therefore, we perform a meta-analysis to get a more precise estimation of this association. The association between ABC polymorphisms and osteosarcoma response was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Three polymorphisms of ABC including ABCB1 rs1128503, ABCC3 rs4148416 and ABCC2 rs717620 polymorphism were investigated. Overall, significant association was observed between ABCC3 rs4148416 polymorphism and osteosarcoma response under allele contrast (T vs. C: OR=1.73, 95%CI=1.09-2.74, P=0.019), homozygote comparison (TT vs. CC: OR=2.00, 95%CI=1.25-3.23, P=0.004), recessive genetic model (TT vs. TC/CC: OR=1.80, 95%CI=1.14-2.84, P=0.011) and dominant genetic model (TT/TC vs. CC: OR=1.70, 95%CI=1.20-2.42, P=0.003). Moreover, significant association was also observed in Caucasian population rather than Asian population for ABCB1 rs1128503 polymorphism. We conclude that ABCC3 rs4148416 polymorphism was significantly associated with poor osteosarcoma response and ABCB1 rs1128503 polymorphism was significantly associated with good osteosarcoma response in Caucasian population rather than Asian population.