Hesperidin, a flavonoid derived from citrus fruits, has been reported to show various biological effects including anticancer activity. This study investigated whether hesperidin affected the proliferation of MCF-7 human breast cancer cells transfected with green fluorescent protein (GFP)/alpha-tubulin (MCF-7-GFP-Tubulin cells), androgen-independent PC-3 and DU-145 prostate cancer cells, and androgen-dependent LNCaP prostate cancer cells. The results were as follows. (1) Hesperidin inhibited the proliferation of MCF-7-GFP-Tubulin cells, probably not through an antimitotic mechanism. (2) Hesperidin also inhibited both basal and testosterone-induced proliferation of LNCaP cells. (3) However, hesperidin did not significantly affect the cell proliferation of two hormone-independent prostate cancer cells, PC-3 and DU-145. It is concluded that hesperidin can inhibit the proliferation of breast cancer cells through mechanisms other than antimitosis and it is suggested that hesperidin be further investigated for the possible interaction with androgenic receptors and involvement in signaling pathway after receptor binding in prostate cancer cells through future research.

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Purpose: Niclosamide, an FDA-approved anthelmintic drug, has been characterized as a potent Wnt inhibitor that can suppress tumor growth and cancer stem-like cell (CSC) populations. However, the underlying molecular mechanisms remain poorly understood. This study aimed to examine how Wnt inhibition by niclosamide preferentially targets CSCs.Experimental Design: The mechanistic role of niclosamide in CSC inhibition was examined in public databases, human colorectal cancer cells, colorectal cancer xenografts, and azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colorectal cancer model.Results: Niclosamide suppresses CSC populations and their self-renewal activities in colorectal cancer cells, and this CSCtargeting effect leads to irreversible disruption of tumorinitiating potential in vivo. Mechanistically, niclosamide downregulates multiple signaling components of the Wnt pathway, specifically lymphoid enhancer-binding factor 1 (LEF1) expression, which is critical for regulating stemness. Subsequently, we identified that the doublecortin-like kinase 1 (DCLK1)-B is a target of LEF1 and upregulates cancer stemness in colorectal cancer cells. We first documented that niclosamide blocks the transcription of DCLK1-B by interrupting the binding of LEF1 to DCLK1-B promoter. DCLK1-B depletion impairs cancer stemness resulting in reduced survival potential and increased apoptosis, thus sensitizing colorectal cancer to chemoradiation.Conclusions: Disruption of the LEF1/DCLK1-B axis by niclosamide eradicates cancer stemness and elicits therapeutic effects on colorectal cancer initiation, progression, and resistance. These findings provide a preclinical rationale to broaden the clinical evaluation of niclosamide for the treatment of colorectal cancer.

In this study, there was a 2-month interval between the lowest value of the maximal amplitude of the surface electromyography and the maximal clinical effects following botulinum toxin A injection, and there was similarity between the recovery of the masseter function and the diminution of the clinical effect. The clinical effect of botulinum toxin A persisted for 12 months after treatment on physical measurements, and the authors felt that this long-lasting effect of botulinum toxin A beyond expectation could be explained by incomplete recovery of muscle function.

Ossification of the posterior longitudinal ligament (OPLL) can be defined as an ectopic ossification in the tissues of spinal ligament showing a hyperostotic condition. OPLL is developed mostly in the cervical spine and clinical presentations of OPLL are majorly myelopathy and/or radiculopathy, with serious neurological pathology resulting in paralysis of extremities and disturbances of motility lowering the quality of life. OPLL is known to be an idiopathic and multifactorial disease, which genetic factors and non-genetic factors including diet, obesity, physical strain on the posterior longitudinal ligament, age, and diabetes mellitus, are involved into the pathogenesis. Up to now, surgical management by decompressing the spinal cord is regarded as standard treatment for OPLL, although there might be the risk of development of reprogression of ossification. The molecular pathogenesis and efficient therapeutic strategy, especially pharmacotherapy and/or preventive intervention, of OPLL has not been clearly elucidated and suggested. Therefore, in this review, we tried to give an overview to the present research results on OPLL, in order to shed light on the potential pharmacotherapy based on molecular pathophysiologic aspect of OPLL, especially on the genetic/genomic factors involved into the etiology of OPLL.

In this study, we investigated whether apigenin and wogonin affect MUC5AC mucin production and gene expression induced by phorbol ester (phorbol 12-myristate 13-acetate, PMA) or epidermal growth factor (EGF) from human airway epithelial cells. Confluent NCI-H292 cells were pretreated with each agent for 30 min and then stimulated with PMA or EGF for 24 h, respectively. MUC5AC mucin gene expression and mucin protein production were measured by reverse transcription polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA). The results were as follows: (i) apigenin and wogonin were found to inhibit the production of MUC5AC mucin protein induced by PMA or EGF; (ii) both compounds also inhibited the expression of MUC5AC mucin gene induced by PMA or EGF. These results suggest that apigenin and wogonin can inhibit mucin gene expression and production of mucin protein, by directly acting on airway epithelial cells.

This study investigated whether genistein and curcumin affect epidermal growth factor (EGF)-induced MUC5AC mucin production and gene expression from human airway epithelial cells. Confluent NCI-H292 cells were pretreated with each agent for 30 min and then stimulated with EGF for 24 h. The MUC5AC mucin gene expression and mucin protein production were measured by reverse transcription - polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The results were as follows: (1) genistein and curcumin inhibited the production of MUC5AC mucin protein induced by EGF, dose-dependently; (2) genistein and curcumin also inhibited the expression of MUC5AC mucin gene induced by EGF. This result suggests that genistein and curcumin can regulate mucin gene expression and production of mucin protein induced by EGF, by directly acting on airway epithelial cells.

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