• Applied Microscopy
• /
• v.38 no.3
• /
• pp.245-250
• /
• 2008

Etoposide (Eto) is chemotherapeutic compounds that is currently used in the treatment of metastatic prostate cancer but new therapeutic agents are needed for the treatment of androgen-independent prostate cancer. The objective of the present study was to determine whether vitamin C (VC), the antioxidant, plays a role in regulating the growth of prostate cancer cell lines and whether VC has synergistic effect to tumor cell killing by chemotherapeutic drugs. Androgen-dependent LNCaP and androgen-independent DU-145 prostate cancer cell lines were used in this study. Both cells presented increase of dose- and time-dependent cytotoxicity in Eto-treated cultures. The combined treatment with Eto and VC significantly increased the percentage of apoptotic cells compared to Eto-treated cells(p<0.05). The present findings demonstrated that VC inhibited the growth of prostate cancer cell lines by Eto-mediated cytotoxicity and induced apoptosis. These results suggest that the chemotherapeutic effect of Eto on prostate cancer can be enhanced by VC.

• Clinical and Experimental Pediatrics
• /
• v.57 no.10
• /
• pp.434-439
• /
• 2014

Treatment outcomes of pediatric cancers have improved greatly with the development of improved treatment protocols, new drugs, and better supportive measures, resulting in overall survival rates greater than 70%. Survival rates are highest in acute lymphoblastic leukemia, reaching more than 90%, owing to risk-based treatment through multicenter clinical trials and protocols developed to prevent central nervous system relapse and testicular relapse in boys. New drugs including clofarabine and nelarabine are currently being evaluated in clinical trials, and other targeted agents are continuously being developed. Chimeric antigen receptor-modified T cells are now attracting interest for the treatment of recurrent or refractory disease. Stem cell transplantation is still the most effective treatment for pediatric acute myeloid leukemia (AML). However, in order to reduce treatment-related death after stem cell transplantation, there is need for improved treatments. New drugs and targeted agents are also needed for improved outcome of AML. Surgery and radiation therapy have been the mainstay for brain tumor treatment. However, chemotherapy is becoming more important for patients who are not eligible for radiotherapy owing to age. Stem cell transplant as a means of high dose chemotherapy and stem cell rescue is a new treatment modality and is often repeated for improved survival. Drugs such as temozolomide are new chemotherapeutic options. In order to achieve 100% cure in children with pediatric cancer, every possible treatment modality and effort should be considered.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.1
• /
• pp.131-133
• /
• 2016

Background: Combination chemotherapy regimes are common treatments for cancer. The aim of this study was to evaluation the effect of individual chemotherapeutic agents in comparison with a first line chemotherapy regime treatment in the AGS gastric cancer cell line by MTT assay. Materials and Methods: In this experimental study, AGS cells were grown in RPMI-1640 supplemented with 10% fetal calf serum and 100 IU/ml penicillin, and $10{\mu}g/ml$ streptomycinin, under a humidified condition at $37^{\circ}C$ with 5% CO2. All cells were washed with PBS and detached with trypsin, centrifuged and 8000 cells re-plated on to 96- well plates. LD50 doses of Epirubicin, Cisplatin and 5-fluorouracil were added to each well in mono or triple therapy. Anti-proliferative activities were determined by MTT assay after 24, 48 or 72 h. Results: Results of MTT assays showed that there were no significant differences among 3 drugs in monotherapy (p=0.088), but there was significant difference between combination therapy with epirubicin (P=0.031) and 5FU (p=0.013) on cell survival at 24 h. After 48 and 72 hours, cell viability showed significant differences between the 3 drugs (p=0.048 and P=0.000 for 48 and 72 h, respectively) and there was significant difference between combination therapy with epirubicin (P=0.035 and P=0.002 for 48 and 72 h, respectively). Conclusions: The results showed no significant differences between these chemotherapy drugs each given alone, but combination therapy with 3 drugs had significant effects on cell viability in comparison with epirubicin alone.

• Journal of Life Science
• /
• v.21 no.11
• /
• pp.1641-1651
• /
• 2011

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L) is a recently identified member of the TNF ligand family that can initiate apoptosis through the activation of their death receptors. TRAIL has been paid attention as a potential anti-cancer drug, because it selectively induces apoptosis in tumor cells in vitro and in vivo but not in most normal cells. However, recent studies have shown that some cancer cells including malignant renal cell carcinoma and hepatocellular carcinoma, are resistant to the apoptotic effects of TRAIL. Therefore, single treatment with TRAIL may not be sufficient for the treatment of various malignant tumor cells. Understanding the molecular mechanisms of TRAIL resistance and identification of sensitizers capable of overcoming TRAIL resistance in cancer cells is needed for the establishment of more effective TRAIL-based cancer therapies. Chemotherapeutic drugs induce apoptosis and the upregulation of death receptors or activation of intracellular signaling pathways of TRAIL. Numerous chemotherapeutic drugs have been shown to sensitize tumor cells to TRAIL-mediated apoptosis. In this study, we summarize biological agents and drugs that sensitize tumors to TRAIL-mediated apoptosis and discuss the potential molecular basis for their sensitization.

• Journal of Microbiology and Biotechnology
• /
• v.30 no.1
• /
• pp.101-108
• /
• 2020

Infections by herpes simplex viruses have an immense impact on humans, ranging from self-limiting, benign illness to serious, life-threatening diseases. While nucleoside analog drugs are available, resistance has been increasing and currently no vaccine exists. Ginsenosides derived from Panax ginseng have been documented to inhibit several viruses and bolster immune defenses. This study evaluated 12 of the most relevant ginsenosides from P. ginseng for toxicities and inhibition of herpes simplex viruses types 1 and 2 in Vero cells. The effects of test compounds and virus infection were determined using a PrestoBlue cell viability assay. Time course studies were also conducted to better understand at what points the virus life cycle was affected. Non-toxic concentrations of the ginsenosides were determined and ranged from 12.5 μM to greater than 100 μM. Ginsenoside 20(S)-Rg3 demonstrated the greatest inhibitory effect and was active against both HSV-1 and HSV-2 with an IC₅₀ of approximately 35 μM. The most dramatic inhibition-over 100% compared to controls-occurred when the virus was exposed to 20(S)-Rg3 for 4 h prior to being added to cells. 20(S)-Rg3 holds promise as a potential chemotherapeutic agent against herpes simplex viruses and, when used together with valacyclovir, may prevent increased resistance to drugs.

• Biomedical Science Letters
• /
• v.29 no.3
• /
• pp.178-183
• /
• 2023

Natural killer (NK) cells are innate cytotoxic lymphoid cells that actively prevent neoplastic development, growth, and metastatic dissemination in a process called cancer immunosurveillance. Regulation of the cytotoxic activity of NK cells relies on integrated interactions between inhibitory receptors and numerous activating receptors that act in tandem to eliminate tumor cells efficiently. Conventional chemotherapy is designed to produce an anti-proliferative or cytotoxic effect on early tumor cell division. Therapies designed to kill cancer cells and simultaneously maintain host anti-tumor immunity are attractive strategies for controlling tumor growth. Depending on the drug and dose used, several chemotherapeutic agents cause DNA damage and cancer cell death through apoptosis, immunogenic cell death, or other forms of non-killing (i.e., mitotic catastrophe, senescence, autophagy). Among stress-induced immunostimulatory proteins, changes in the expression levels of NK cell activating and inhibitory ligands and tumor cell death receptors play an important role in the detection and elimination by innate immune effectors including NK cells. Therefore, we will address how these cytotoxic lymphocytes sense and respond to high and low concentrations of drug-induced stress to the drug cisplatin, among the various types of drugs that contribute to their anticancer activity.

• Journal of Korean Neurosurgical Society
• /
• v.42 no.5
• /
• pp.392-399
• /
• 2007

Objective : Arsenic trioxide ($As_2O_3$) has been used as an anticancer agent in traditional Chinese medicine for thousand years and berberine is an isoquinoline alkaloid present that has indicated significant antimicrobial activity. We have examined the combined anticancer effects of $As_2O_3$ and berberine against the human neuroblastoma (HNB) SH-SY5Y cells in vitro, and to elucidate underlying molecular mechanism. Methods : HNB SH-SY5Y cells were treated with $2\;{\mu}M\;As_2O_3$ and $75\;{\mu}g/ml$ berberine, and their survival, cell death mechanism as well as synergistic cytotoxic effects were estimated by using MTT assay, DAPI staining, agarose gel electrophoresis, flow cytometric analysis, and western blot analysis. Results : The combined treatment of two drugs also markedly decreased cell viability. The cytotoxic effects of two drugs were revealed as apoptosis characterized by chromatin condensation, DNA fragmentation, and the loss of mitochondrial membrane potential. The apoptotic cytotoxicity was accompanied by activation of caspase-3 protease as well as decreased the expression of Bcl-2, Bid, and Bcl-x/L. In addition, the cells treated with combination of two drugs also showed significantly increased intracellular reactive oxygen species levels and lipid peroxidation compared to cells $As_2O_3$or berberine only. Conclusion : Combined treatment of $As_2O_3$ with berberine induced activation of apoptotic signaling pathways in HNB SH-SY5Y cells. These results suggest that the possibility of the combined treatment of two chemotherapeutic agents with low concentration improving cytotoxic effect for cancer cells with minimal side effects.

• Natural Product Sciences
• /
• v.26 no.1
• /
• pp.28-49
• /
• 2020

The efficacy and side effects associated with anticancer drugs have attracted an extensive research focus. Onconephrology is an evolving field of nephrology that deals with the study of kidney diseases in cancer patients. Most renal diseases in cancer patients are unique, and management of renal disease can be challenging especially in the presence of continuing use of the nephrotoxic drugs. Cisplatin is one of the most important chemotherapeutic agents used in the treatment of various malignancies, such as head, neck, ovarian, and cervical cancers. The major limitation in the clinical use of cisplatin is its tendency to induce adverse effects, such as nephrotoxicity. Recently, plant-derived phytochemicals have emerged as novel agents providing protection against cisplatin-induced renal cytotoxicity. Owing to the diversity of phytochemicals, they cover a wide spectrum of therapeutic indications in cancer and inflammation and have been a productive source of lead compounds for the development of novel medications. Of these agents, the effectiveness of triterpenoids, isolated from various medicinal plants, against cisplatin-induced renal cytotoxicity has been reported most frequently compared to other phytochemicals. Triterpenes are one of the most numerous and diverse groups of plant natural products. Triterpenes ameliorate cisplatin-induced renal damage through multiple pathways by inhibiting reactive oxygen species, inflammation, down-regulation of the MAPK, apoptosis, and NF-κB signaling pathways and upregulation of Nrf2-mediated antioxidant defense mechanisms. Here, we reviewed recent findings on the natural compounds with protective potential in cisplatin-induced renal cytotoxicity, provided an overview of the protective effects and mechanisms that have been identified to date, and discussed strategies to reduce renal cytotoxicity induced by anticancer drugs.

• 제어로봇시스템학회:학술대회논문집
• /
• 2004.08a
• /
• pp.330-335
• /
• 2004

Phase specific models for cancer chemotherapy are described as optimal control problems. We review earlier results on scheduling optimal therapies when the controls represent the effectiveness of chemotherapeutic agents, or, equivalently, when the simplifying assumption is made that drugs act instantaneously. In this paper we discuss how to incorporate more realistic medical aspects which hitherto have been neglected in the models. They include pharmacokinetic equations (PK) which model the drug's plasma concentration and various pharmacodynamic models (PD) which describe the effect the concentrations have on cells. We also briefly discuss the important medical issue of drug resistance.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.19
• /
• pp.8007-8018
• /
• 2014

Cervical cancer is the most common gynecologic malignancy worldwide and development of new therapeutic strategies and anticancer agents is an urgent priority. Plants have remained an important source in the search for novel cytotoxic compounds and several polyphenolic flavonoids possess antitumor properties. In this review article, data about potential anticarcinogenic activity of common natural flavonoids on various human cervical cancer cell lines are compiled and analyzed showing perspectives for the use of these secondary metabolites in the treatment of cervical carcinoma as well as in the development of novel chemotherapeutic drugs. Such anticancer effects of flavonoids seem to differentially depend on the cellular type and origin of cervical carcinoma creating possibilities for specific targeting in the future. Besides the cytotoxic activity per se, several flavonoids can also contribute to the increase in efficacy of conventional therapies rendering tumor cells more sensitive to standard chemotherapeutics and irradiation. Although the current knowledge is still rather scarce and further studies are certainly needed, it is clear that natural flavonoids may have a great potential to benefit cervical cancer patients.