Anticancer Activity and Underlying Mechanism of Phytochemicals against Multiple Myeloma.

Multiple myeloma (MM)-a common hematologic malignancy of plasma cells-accounts for substantial mortality and morbidity rates. Due to the advent of novel therapies such as immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and monoclonal antibodies (mAbs), response rates were increased and free survival and overall survival have been elevated. However, adverse events including toxicity, neuropathy or continuous relapse are still problems. Thus, development of novel drugs which have less side effects and more effective is needed. This review aims to recapitulate the pharmacologic anti-MM mechanisms of various phytochemicals, elucidating their molecular targets. Keywords related to MM and natural products were searched in PUBMED/MEDLINE. Phytochemicals have been reported to display a variety of anti-MM activities, including apoptosis, cell cycle arrest, antiangiogenesis, and miRNA modulation. Some phytochemicals sensitize the conventional therapies such as dexamethasone. Also, there are clinical trials with phytochemicals such as agaricus, curcumin, and Neovastat regarding MM treatment. Taken together, this review elucidated and categorized the evidences that natural products and their bioactive compounds could be potent drugs in treating MM.

MiR-657/ATF2 Signaling Pathway Has a Critical Role in Spatholobus suberectus Dunn Extract-Induced Apoptosis in U266 and U937 Cells.

Though Spatholobus suberectus Dunn (SSD) has been reported to have anti-virus, anti-osteoclastogenesis, and anti-inflammation activities, its underlying anti-cancer mechanism has never been elucidated in association with the role of miR-657 in endoplasmic reticulum (ER) stress-related apoptosis to date. SSD treatment exerted cytotoxicity in U266 and U937 cells in a dose-dependent manner. Also, apoptosis-related proteins such as PARP, procaspase-3, and Bax were regulated by SSD treatment. Furthermore, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay revealed that a number of apoptotic bodies were increased by SSD. Interestingly, the ER stress-related proteins such as p-ATF2 and CHOP were elevated by SSD. Interestingly, reactive oxygen species (ROS) generation and cytotoxicity by SSD treatment were significantly reduced by N-Acetyl-L-cysteine (NAC). Among the microRNAs (miRNAs) regulated by SSD treatment, miR-657 was most significantly reduced by SSD treatment. However, an miR-657 mimic reversed SSD-induced apoptosis by the attenuation of the expression of p-ATF2, CHOP, and PARP cleavage. Overall, these findings provide scientific evidence that miR657 is an onco-miRNA targeting the ER stress signal pathway and SSD induces apoptosis via the inhibition of miR-657, ROS, and the activation of p-ATF2 and CHOP as a potent anti-cancer agent for myeloid-originated hematological cancer.

Psychophysical and psychophysiological effects of heat stimulation by electric moxibustion.

OBJECTIVES: Traditional moxibustion might be not safe due to the excessive heat stimulation or toxic chemical components involved. Electric moxibustion (EM), which has been recently developed as an alternative, offers adjustable and constant heat stimulation. This study aimed to investigate the psychophysical and psychophysiological responses to EM heat stimulation. METHODS: Twenty-seven healthy volunteers received two different levels of heat stimulation using EM. High-temperature (HT) and medium-temperature (MT) heat stimulations were randomly delivered at the TE5 acupoint on the left or right arm. Participants rated the intensity and the spatial information of the heat sensations immediately after each EM stimulation. Local blood flow around the acupoint was measured with Laser Doppler perfusion imaging before and after heat stimulation. RESULTS: Both HT-EM and MT-EM induced considerable heat sensations and enhanced local blood flow around the acupoints. HT-EM resulted in greater heat sensation compared to MT-EM. HT-EM induced a higher increase in local blood flow around the stimulation site compared to MT-EM. No remarkable adverse effects were noted. CONCLUSION: Two different levels of EM heat stimulation induced two different levels of heat sensations and enhanced local blood flow. This preliminary study suggests that the newly developed EM can be further applied to examine the effectiveness of moxibustion in clinical trials.

miR-211 Plays a Critical Role in Cnidium officinale Makino Extract-Induced, ROS/ER Stress-Mediated Apoptosis in U937 and U266 Cells.

Though Cnidium officinale Makino (COM) was known to have anti-angiogenic, anti-oxidant, neuroprotective, and anti-cancer effects, the underlying anticancer mechanism of COM using endoplasmic reticulum (ER) stress and miRNA remained unclear until now. Thus, in the current study, the inhibitory mechanism of COM in lymphoma and multiple myeloma (MM) cells was elucidated. COM exerted cytotoxicity in U937 and U266 but not Raw264.7 cells. COM treatment increased the expression of ER stress-related proteins such as p-protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), p-eukaryotic initiation factor (p-eIF2α), and activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP). COM also cleaved poly (ADP-ribose) polymerase (PARP) in a dose-dependent manner in both cells. Also, reactive oxygen species (ROS) generation was elevated by COM treatment. Conversely, the apoptotic effect of COM treatment was blocked by N-acetyl-l-cysteine (NAC) pretreatment. Also, the pro-survival miRNA, miR-211 was decreased by COM treatment in U937 and U266 cells. miR-211 mimic attenuated COM-induced apoptosis. Taken together, these results support the scientific evidence that COM induces apoptosis via ROS generation/CHOP activation and miR-211 suppression in U937 and U266 cells.

Review of Natural Product-Derived Compounds as Potent Antiglioblastoma Drugs.

Common care for glioblastoma multiforme (GBM) is a surgical resection followed by radiotherapy and temozolomide- (TMZ-) based chemotherapy. Unfortunately, these therapies remain inadequate involving severe mortality and recurrence. Recently, new approaches discovering combinations of multiple inhibitors have been proposed along with the identification of key driver mutations that are specific to each patient. To date, this approach is still limited by the lack of effective therapy. Hopefully, novel compounds derived from natural products are suggested as potential solutions. Inhibitory effects of natural products on angiogenesis and metastasis and cancer suppressive effect of altering miRNA expression are provident discoveries. Angelica sinensis accelerates apoptosis by their key substances influencing factors of apoptosis pathways. Brazilin displays antitumor features by making influence on reactive oxygen species (ROS) intensity. Sargassum serratifolium, flavonoids, and so on have antimetastasis effect. Ficus carica controls miRNA that inhibits translation of certain secretory pathway proteins during the UPR. Serratia marcescens and patupilone (EPO 906) are physically assessed materials through clinical trials related to GBM progression. Consequently, our review puts emphasis on the potential of natural products in GBM treatment by regulating multiple malignant cancer-related pathway solving pending problem such as reducing toxicity and side effect.