Cancer cells can acquire an anticancer, drug-resistant phenotype following chemotherapy, which is tightly linked to cancer malignancy and patient survival rates. Therefore, the identification of options to treat chemotherapy‑resistant cancer cells is an urgent requirement. Rubus coreanus Miquel (RCM) has long been used as a source of food. In addition, it has been reported that RCM has effective functions against particular diseases, including cancer and inflammation. In the present study, it was demonstrated that RCM extract caused the apoptotic cell death of doxorubicin‑resistant NCI/ADR‑RES ovarian cancer cells by phosphorylating c‑Jun N‑terminal kinase (JNK). The RCM‑mediated reduction of cell viability showed no synergism with doxorubicin. In addition, ellagic acid and quercetin, which are phytochemicals found in RCM, also caused apoptosis of the NCI/ADR‑RES cells. In subsequent investigations of the RCM‑altered signaling pathway, RCM extract, ellagic acid and quercetin were found to commonly induce the phosphorylation of JNK and AKT. Additionally, the inhibition of JNK with SP600125 repressed the apoptotic cell death induced by RCM extract, ellagic acid and quercetin, and the inhibition of JNK appeared to switch apoptosis to necrosis. JNK inhibition also reduced the phosphorylation of AKT, which was induced by RCM extract, ellagic acid and quercetin, suggesting that the phosphorylation of JNK is required for AKT phosphorylation in RCM‑, ellagic acid‑ or quercetin‑induced apoptotic cell death. Therefore, the data obtained in the present study led to the conclusion that RCM caused apoptosis of doxorubicin‑resistant NCI/ADR-RES ovarian cancer cells via JNK phosphorylation, and suggested that RCM may be effective in the treatment of chemotherapy‑resistant cancer cells.

Progression of chronic myeloid leukemia, marked by the oncogenic Bcr-Abl mutation, is tightly associated with an alteration of the p53 pathway. It is known that butein extracted from various plants represses cancer growth. Although the anticancer effects of butein are widely accepted, the mechanisms by which butein induces apoptosis of chronic myeloid leukemia cells remains to be elucidated. The present study demonstrated that butein-induced apoptosis was mediated by p53. KBM5 chronic myeloid leukemia (CML) cells expressing wild-type p53 were more sensitive to butein compared with p53-null K562 CML cells in terms of apoptotic cell death. In addition, butein arrested KBM5 cells at S-phase and altered the expression levels of certain cyclins and the p53-downstream targets, MDM2 and p21. In addition, while butein reduced the protein expression of MDM2 in the KBM5 and K562 cells, it resulted in proteasome-independent MDM2 degradation in p53-expressing KBM5 cells, however, not in p53-null K562 cells. Therefore, the present study suggested that p53 causes the butein-mediated apoptosis of leukemic cells.

Chemotherapy frequently causes anorexia in cancer patients, which has been associated with poor disease prognosis. Several therapeutic strategies for the treatment of chemotherapy‑induced anorexia are available; however, their adverse effects limit their clinical use. Herbal medicines have a long history of use for the treatment of various diseases, including cancer, and recent research has demonstrated their safety and efficacy. In the present study, combinations of herbal medicines were designed based on traditional Korean medicine, and their effects were investigated on chemotherapy‑induced anorexia. Herbal mixtures were extracted, composed of Atractylodes japonica, Angelica gigas, Astragalus membranaceus, Lonicera japonica Thunb., Taraxacum platycarpum H. Dahlstedt and Prunella vulgaris var. asiatica (Nakai) Hara. The mixtures were termed LCBP‑Anocure‑16001‑3 (LA16001, LA16002, LA16003). A cisplatin‑induced anorexic mouse model was used to evaluate the putative effects of the extracts on chemotherapy‑induced anorexia. Treatment with LA16001 was revealed to prevent body weight loss, and all three extracts were demonstrated to improve food intake. When the molecular mechanisms underlying the orexigenic effects of LA16001 were investigated, altered expression levels of ghrelin, leptin and interleukin‑6 were revealed. Furthermore, LA16001 was reported to induce phosphorylation of Janus kinase 1 and signal transducer and activator of transcription 3. In addition, LA16001 administration increased the number of white blood cells and neutrophils. These results suggested that the herbal formula LA16001 may be able to prevent chemotherapy‑induced anorexia and may have potential as a novel therapeutic strategy for the adjuvant treatment of patients with cancer.

Abstract. Canonical WNT signaling promotes breast cancer progression. Although APC downregulated 1 (APCDD1) may inhibit canonical WNT signaling, its role in breast cancer remains to be fully understood. The present study demonstrated that APCDD1 suppressed in vitro breast cancer growth and metastasis by inhibiting canonical WNT signaling. The present study demonstrated that APCDD1 expression was negatively associated with breast cancer cell invasion, which was consistent with previous studies that indicated that APCDD1 expression was decreased in invasive ductal carcinoma compared with that in ductal carcinoma in situ. Furthermore, APCDD1 expression was negatively associated with nuclear β-catenin expression and transcription factor/lymphoid enhancer binding factor 1 transcriptional activity in the present study. Silencing APCDD1 in non-invasive breast cancer cells using lentiviral APCDD1 short hairpin RNAs enhanced migration and invasion, which may be mediated by canonical WNT signaling, whereas the overexpression of human influenza hemagglutinin-tagged APCDD1 in invasive breast cancer cells repressed these properties. Therefore, the present study suggested that APCDD1 regulated breast cancer progression by targeting canonical WNT signaling and modulating breast cancer cell invasion. IntroductionThe WNT signaling pathway is associated with numerous biological events, including embryonic development and adult tissue homeostasis. Therefore, abnormal WNT signaling is associated with diseases, including certain types of cancer (1,2). WNTs activate the canonical and non-canonical signaling pathways, which are mutually exclusive. The canonical WNT signaling pathway triggers β-catenin-dependent transcriptional regulation, whereas the non-canonical WNT signaling pathway activates the β-catenin-independent signaling pathway (1,2).The canonical WNT signaling pathway regulates normal breast development, and its deregulation is associated with breast cancer progression (3,4). WNTs aid in the generation of the canonical WNT signaling pathway by binding to the coreceptors LDL receptor-related protein (LRP)5/6 and frizzled on the cell surface, and activating the β-catenin/t-cell factor (TCF) complex (2). Overexpression of Wnt1, which may be induced by the integration of the mouse mammary tumor virus, triggers mammary tumor development (5,6). Autocrine WNT signaling regulates mammary epithelial cell fate by regulating renewal and the epithelial-to-mesenchymal transition (EMT), thereby affecting tumorigenesis and metastasis in a deregulated signaling state (7,8). Accordingly, the WNT-activated β-catenin/TCF complex potentiates breast cancer metastasis by altering the expression of genes associated with EMT (9,10).Previous studies have revealed multiple inhibitors of the canonical WNT signaling pathway, including secreted frizzled-related protein (SFRP), dickkopf (DKK), and WNT inhibitory factor (WIF) (2,11). In addition, APC downregulated 1 (APCDD1) may inhibit the canonical WNT signaling pathway by directly binding WNT3A and L...

Abstract. Cancer remains a leading cause of mortality worldwide, therefore food products are being investigated for potential prevention or treatment strategies. The ingredient, barley grass extract (Hordeum vulgare L.; Bex) is used to prevent or ameliorate various types of disease. In cancer, Bex has been revealed to inhibit tumor growth. However, its effect on cancer cells is yet to be clearly defined. In the present study, the effect of Bex on cancer cell growth was investigated. Bex inhibited the viabilities of breast and prostate cancer cells according to the results of MTT assays. Accordingly, Bex caused apoptosis, which was confirmed by Annexin V staining and western blot analysis for poly (ADP-ribose) polymerase and caspases. Furthermore, Bex increased the intracellular levels of reactive oxygen species (ROS), and N-acetyl-L-cystein blocked Bex-induced apoptosis. Therefore, the study demonstrated that Bex causes apoptosis of breast and prostate cancer cells by increasing intracellular ROS levels. IntroductionCancer is one of the leading causes of mortality worldwide (1,2). Despite numerous cancer studies and the development of various anti-cancer therapeutic agents, cancer remains dangerous. Anti-cancer therapeutic agents are chemically or biologically produced, and their effects are well defined (3-7). However, treatments continue to be associated with adverse effects and the majority of patients have an aversion to them (8).Herbal products have long been used to prevent or treat diseases, including cancer (9-12). Furthermore, certain anti-cancer therapeutic agents that are chemically produced originate from herbal products and their chemical characteristics are modified (7,(12)(13)(14). Typically, patients prefer to take herbal products (15-18); herbal products have historically been used as traditional medicines, such as traditional Chinese and Korean medicines, Kampo medicines and Ayurvedic medicine (13,14,19). Certain herbal products were demonstrated to treat cancer and/or reduce the side effects of cancer treatment (13,(15)(16)(17)(19)(20)(21). Therefore, herbal products are considered to be promising for cancer prevention and treatment.Barley grass extract (Hordeum vulgare L.; Bex) has long been used as a food product. Its biological effects have also been addressed by various in vitro and in vivo studies, although evidence there is limited evidence of the efficacy of Bex against specific conditions (22). The effect of Bex on the immune system was revealed in in vitro and in vivo experimental sets (23-25). Accordingly, Bex inhibited atopic dermatitis in NC/Nga mice by altering the expression levels of cytokines (26). Similarly, Bex repressed lipopolysaccharide-induced inflammation (27). Furthermore, its effect in type 2 diabetes was revealed in a genetically engineered mouse model and patients (28,29). Therefore, the effects of Bex on particular diseases have been demonstrated at least in experimental systems. A previous study revealed that Bex caused apoptosis of leukemia and lymphoma cell lines...