• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.3
• /
• pp.1703-1706
• /
• 2013

Lung cancer remains a deadly disease with unsatisfactory overall survival. Resveratrol (Res) has the potential to inhibit growth of several types of cancer such as prostate and colorectal examples. In the current study, we evaluated in vitro and in vivo anticancer efficiency of Res in a xenograft model with A549 cells. Cell inhibition effects of Res were measured by MTT assay. Apoptotis of A549 cells was assessed with reference to caspase-3 activity and growth curves of tumor volume and bodyweight of the mice were measured every two days. In vitro cytotoxicity evaluation indicated Res to exert dose-dependent cell inhibition effects against A549 cells with activation of caspase-3. In vivo evaluation showed Res to effectively inhibit the growth of lung cancer in a dose-dependent manner in nude mice. Therefore, we believe that Res might be a promising phytomedicine for cancer therapy and further efforts are needed to explore this potential therapeutic strategy.

• BMB Reports
• /
• v.39 no.5
• /
• pp.479-491
• /
• 2006

Heme oxygenase (HO), the rate limiting enzyme in the breakdown of heme into carbon monoxide (CO), iron and bilirubin, has recently received overwhelming research attention. To date three mammalian HO isozymes have been identified, and the only inducible form is HO-1 while HO-2 and HO-3 are constitutively expressed. Advances in unveiling signal transduction network indicate that a battery of redox-sensitive transcription factors, such as activator protein-1 (AP-1), nuclear factor-kappa B (NF-${\kappa}B$) and nuclear factor E2-related factor-2 (Nrf2), and their upstream kinases including mitogen-activated protein kinases play an important regulatory role in HO-1 gene induction. The products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin have been shown to exert protective effects in several organs against oxidative and other noxious stimuli. In this context, it is interesting to note that induction of HO-1 expression contributes to protection against liver damage induced by several chemical compounds such as acetaminophen, carbon tetrachloride and heavy metals, suggesting HO-1 induction as an important cellular endeavor for hepatoprotection. The focus of this review is on the significance of targeted induction of HO-1 as a potential therapeutic strategy to protect against chemically-induced liver injury as well as hepatocarcinogenesis.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.11
• /
• pp.6863-6867
• /
• 2013

Phyllanthus emblica (PE) is known to exhibit various pharmacological properties. This study aimed to evaluate the antimetastatic potential of a PE aqueous extract. Cytotoxicity to human fibrosarcoma cells, HT1080, was determined by viability assay using the 3-(4,5-dimethylthiazol,2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent. Cell migration and invasion were investigated using chemotaxis chambers containing membranes precoated with collagen IV and Matrigel, respectively. Cell attachment onto normal surfaces of cell culture plates was tested to determine the cell-adhesion capability. The molecular mechanism of antimetastatic activity was assessed by measuring the gene expression of matrix metalloproteinases, MMP2, and MMP9, using reverse transcription-polymerase chain reaction (RT-PCR) assay. The mRNA levels of both genes were significantly down-regulated after pretreatment with PE extract for 5 days. Our findings show the antimetastatic function of PE extract in reducing cell proliferation, migration, invasion, and adhesion in both dose- and time-dependent manners, especially growth arrest with low $IC_{50}$ value. A decrease in the expression of both MMP2 and MMP9 seems to be the cellular mechanism for antimetastasis in this case. There is a high potential to use PE extracts clinically as an optional adjuvant therapeutic drug for therapeutic intervention strategies in cancer therapy or chemoprevention.

• Biomolecules & Therapeutics
• /
• v.26 no.1
• /
• pp.29-38
• /
• 2018

During cancer progression, cancer cells are repeatedly exposed to metabolic stress conditions in a resource-limited environment which they must escape. Increasing evidence indicates the importance of nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis in the survival of cancer cells under metabolic stress conditions, such as metabolic resource limitation and therapeutic intervention. NADPH is essential for scavenging of reactive oxygen species (ROS) mainly derived from oxidative phosphorylation required for ATP generation. Thus, metabolic reprogramming of NADPH homeostasis is an important step in cancer progression as well as in combinational therapeutic approaches. In mammalian, the pentose phosphate pathway (PPP) and one-carbon metabolism are major sources of NADPH production. In this review, we focus on the importance of glucose flux control towards PPP regulated by oncogenic pathways and the potential therein for metabolic targeting as a cancer therapy. We also summarize the role of Snail (Snai1), an important regulator of the epithelial mesenchymal transition (EMT), in controlling glucose flux towards PPP and thus potentiating cancer cell survival under oxidative and metabolic stress.

• Journal of Yeungnam Medical Science
• /
• v.30 no.1
• /
• pp.4-9
• /
• 2013

Leptin, a 16-kDa cytokine, is secreted by adipose tissue in response to the surplus of fat store. Thereby, the brain is informed about the body's energy status. In the hypothalamus, leptin triggers specific neuronal subpopulations (e.g., POMC and NPY neurons) and activates several intracellular signaling events, including the JAK/STAT, MAPK, PI3K, and mTOR pathway, which eventually translates into decreased food intake and increased energy expenditure. Leptin signal is inhibited by a feedback inhibitory pathway mediated by SOCS3. PTP1B involves another inhibitory pathway of leptin. Leptin potently promotes fat mass loss and body weight reduction in lean subjects. However, it is not widely used in the clinical field because of leptin resistance, which is a common feature of obesity characterized by hyperleptinemia and the failure of exogenous leptin administration to provide therapeutic benefit in rodents and humans. The potential mechanisms of leptin resistance include the following: 1) increases in circulating leptin-binding proteins, 2) reduced transport of leptin across the blood-brain barrier, 3) decreased leptin receptor-B (LRB), and/or 4) the provocation of processes that diminish cellular leptin signaling (inflammation, endoplasmic reticulum stress, feedback inhibition, etc.). Thus, interference of the cellular mechanisms that attenuate leptin signaling improves leptin action in cells and animal models, suggesting the potential utility of these processes as points of therapeutic intervention. Various experimental trials and compounds that improve leptin resistance are introduced in this paper.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.13
• /
• pp.5325-5329
• /
• 2015

Farnesiferol C is a natural compound with various anti-cancer properties that belongs to the class of sesquiterpene coumarins. However, the low bioavailability of farnesiferol C limits its therapeutic potential. Here, we overcame this problem utilizing dendrosome nano-particles and evaluated the anti-cancer effect of dendrosomal farnesiferol C (DFC) on the AGS gastric cancer cell line. The 3-(4,5-dimethyl-thiazol-2yl)-2,5- diphenyl tetrazolium bromide (MTT) assay and reverse transcriptase-polymerase chain reaction (RT-PCR) were respectively used to detect the anti-proliferative properties of DFC and expression ratio of Bax/Bcl-2 as a hallmark of apoptosis. Compared to the void farnesiferol C (FC), our data showed that DFC significantly suppresses the proliferation of AGS cells in a time- and dose-dependent manner (P<0.01). Also, DFC meaningfully increased the expression ratio of Bax/Bcl-2 in AGS cells (P<0.01). The findings demonstrate that our nano-based formulation of farnesiferol C could be considered as a potential therapeutic agent in cancer targeting.

• Molecules and Cells
• /
• v.43 no.2
• /
• pp.198-202
• /
• 2020

Comprehensive inhibition of RUNX1, RUNX2, and RUNX3 led to marked cell suppression compared with inhibition of RUNX1 alone, clarifying that the RUNX family members are important for proliferation and maintenance of diverse cancers, and "cluster regulation of RUNX (CROX)" is a very effective strategy to suppress cancer cells. Recent studies reported by us and other groups suggested that wild-type RUNX1 is needed for survival and proliferation of certain types of leukemia, lung cancer, gastric cancer, etc. and for their one of metastatic target sites such as born marrow endothelial niche, suggesting that RUNX1 often functions oncogenic manners in cancer cells. In this review, we describe the significance and paradoxical requirement of RUNX1 tumor suppressor in leukemia and even solid cancers based on recent our findings such as "genetic compensation of RUNX family transcription factors (the compensation mechanism for the total level of RUNX family protein expression)", "RUNX1 inhibition-induced inhibitory effects on leukemia cells and on solid cancers through p53 activation", and "autonomous feedback loop of RUNX1-p53-CBFB in acute myeloid leukemia cells". Taken together, these findings identify a crucial role for the RUNX cluster in the maintenance and progression of cancers and suggest that modulation of the RUNX cluster using the pyrrole-imidazole polyamide gene-switch technology is a potential novel therapeutic approach to control cancers.

• Integrative Medicine Research
• /
• v.5 no.3
• /
• pp.176-181
• /
• 2016

Recent studies have focused on evidence-based interventions to prevent mobility decline and enhance physical performance in older adults. Several modalities, in addition to traditional strengthening programs, have been designed to manage age-related functional decline more effectively. In this study, we reviewed the current relevant literatures to assess the therapeutic potential of eccentric exercises for age-related muscle atrophy (sarcopenia). Age-related changes in human skeletal muscle, and their relationship with physical performance, are discussed with reference to in vitro physiologic and human biomechanics studies. An overview of issues relevant to sarcopenia is provided in the context of the recent consensus on the diagnosis and management of the condition. A decline in mobility among the aging population is closely linked with changes in the muscle force-velocity relationship. Interventions based specifically on increasing velocity and eccentric strength can improve function more effectively compared with traditional strengthening programs. Eccentric strengthening programs are introduced as a specific method for improving both muscle force and velocity. To be more effective, exercise interventions for older adults should focus on enhancing the muscle force-velocity relationship. Exercises that can be performed easily, and that utilize eccentric strength (which is relatively spared during the aging process), are needed to improve both muscle force and velocity.

• Biomolecules & Therapeutics
• /
• v.27 no.5
• /
• pp.466-473
• /
• 2019

Angelica gigas has been used as a Korean traditional medicine for pain relief and gynecological health. Although the extracts are reported to have an anti-inflammatory property, the bioactive compounds of the herbal plant and the effect on T cell responses are unclear. In this study, we identified decursinol angelate (DA) as an immunomodulatory ingredient of A. gigas and demonstrated its suppressive effect on type 17 helper T (Th17) cell responses. Helper T cell culture experiments revealed that DA impeded the differentiation of Th17 cells and IL-17 production without affecting the survival and proliferation of CD4 T cells. By using a dextran sodium sulfate (DSS)-induced colitis model, we determined the therapeutic potential of DA for the treatment of ulcerative colitis. DA treatment attenuated the severity of colitis including a reduction in weight loss, colon shortening, and protection from colonic tissue damage induced by DSS administration. Intriguingly, Th17 cells concurrently with neutrophils in the colitis tissues were significantly decreased by the DA treatment. Overall, our experimental evidence reveals for the first time that DA is an anti-inflammatory compound to modulate inflammatory T cells, and suggests DA as a potential therapeutic agent to manage inflammatory conditions associated with Th17 cell responses.

• Molecules and Cells
• /
• v.42 no.9
• /
• pp.628-636
• /
• 2019

Altered genetic features in cancer cells lead to a high rate of aerobic glycolysis and metabolic reprogramming that is essential for increased cancer cell viability and rapid proliferation. Pyruvate kinase muscle (PKM) is a rate-limiting enzyme in the final step of glycolysis. Herein, we report that PKM is a potential therapeutic target in triple-negative breast cancer (TNBC) cells. We found that PKM1 or PKM2 is highly expressed in TNBC tissues or cells. Knockdown of PKM significantly suppressed cell proliferation and migration, and strongly reduced S phase and induced G2 phase cell cycle arrest by reducing phosphorylation of the CDC2 protein in TNBC cells. Additionally, knockdown of PKM significantly suppressed $NF-{\kappa}B$ (nuclear factor kappa-light-chain-enhancer of activated B cells) activity by reducing the phosphorylation of p65 at serine 536, and also decreased the expression of $NF-{\kappa}B$ target genes. Taken together, PKM is a potential target that may have therapeutic implications for TNBC cells.