Genistein, a major isoflavone compound in soybeans, has been shown to have biological activities including anti‐cancer activates. In the present, we investigated the anti‐leukemia activity of ...genistein on HL‐60 cells in vitro. The percentage of viable cell, cell cycle distribution, apoptotic cell death, reactive oxygen species (ROS), and Ca2+ production and the level of ΔΨm were measured by flow cytometric assay. Cell apoptosis and endoplasmic reticulum (ER) stress associated protein expressions were examined by Western blotting assay. Calpain 1, GRP78, and GADD153 expression were measured by confocal laser microscopy. Results indicated that genistein‐induced cell morphological changes, decreased the total viable cells, induced G2/M phase arrest and DNA damage and fragmentation (cell apoptosis) in HL‐60 cells. Genistein promoted ROS and Ca2+ productions and decreased the level of ΔΨm in HL‐60 cells. Western blotting assay demonstrated that genistein increased ER stress‐associated protein expression such as IRE‐1α, Calpain 1, GRP78, GADD153, caspase‐7, caspase‐4, and ATF‐6α at 20‐50 μM treatment and increased apoptosis associated protein expression such as pro‐apoptotic protein Bax, PARP‐cleavage, caspase‐9, and ‐3, but decreased anti‐apoptotic protein such as Bcl‐2 and Bid in HL‐60 cells. Calpain 1, GRP78, and GADD153 were increased in HL‐60 cells after exposure to 40 μM of genistein. In animal xenografted model, mice were intraperitoneally injected with genistein (0, 0.2, and 0.4 mg/kg) for 28 days and the body weight and tumor volume were recorded. Results showed that genistein did not affect the body weights but significantly reduced the tumor weight in 0.4 mg/kg genistein‐treated group. Genistein also increased the expressions of ATF‐6α, GRP78, Bax, Bad, and Bak in tumor. In conclusion, genistein decreased cell number through G2/M phase arrest and the induction of cell apoptosis through ER stress‐ and mitochondria‐dependent pathways in HL‐60 cells and suppressed tumor properties in vivo.
Benzyl isothiocyanate (BITC), a member of isothiocyanates (ITCs), has been shown to induce cell death in many human cancer cells, but there is no further report to show BITC suppresses glioblastoma ...multiforme cells in vivo. In the present study, we investigate the effects of BITC on the inhibition of GBM 8401/luc2 cell generated tumor on athymic nude mice. We established a luciferase expressing stable clone named as GBM 8401/luc2. Thirty male mice were inoculated subcutaneously with GBM 8401/luc2 cells to generate xenograft tumor mice model. Group I was treated with 110 μL phosphate‐buffered solution plus 10 μL dimethyl sulfoxide, Group II‐III with BITC (5 or 10 μmol/100 μL/day, relatively). Mice were given oral treatment of BITC by gavage for 21 days. Results showed that BITC did not affect the body weights. After anesthetized, the photons emitted from mice tumor were detected with Xenogen IVIS imaging system 200 and higher dose of BITC have low total photon flux than that of lower dose of BITC. Results also showed that higher dose of BITC have low total tumor volumes and weights than that of low dose of BITC. Isolated tumors were investigated by immunohistochemical analysis and results showed that BITC at both dose of treatment weakly stained with anti‐MCL1 and ‐XIAP. However, both dose of BITC treatments have strong signals of caspase‐3 and Bax. Overall, these data demonstrated that BITC suppressed tumor properties in vivo. Overall, based on these observations, BITC can be used against human glioblastoma multiforme in the future.
Abstract Curcumin, a major component of the Curcuma species, is known to have antioxidant, anti-inflammatory properties and induce apoptosis of cancer cells, however, the precise molecular mechanisms ...of apoptosis in vitro are unclear. In this study, we showed that curcumin, a plant product containing the phenolic phytochemical, caused DNA damage and endoplasmic reticulum (ER) stress and mitochondrial-dependent-induced apoptosis through the activation of caspase-3 at a treatment concentration of 30 μM in human lung cancer A-549 cells. In contrast, treatment with 5–10 μM of curcumin did not induce significant apoptosis, but rather induced G2/M-phase arrest in A-549 cells. Flow cytometric analysis indicated that curcumin directly increased intracellular oxidative stress based on the cell permeable dye, 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) acting as an indicator of reactive oxygen species (ROS) generation. GADD153 and GRP78 were increased by curcumin which was indicative of ER stress. Curcumin increased Ca2+ levels and the mitochondrial membrane potential (Δ Ψm ), was decreased in A-549 cells. Overall, our results demonstrated that curcumin treatment causes cell death by activating pathways inducing G2/M-phase arrest and apoptosis.
Antcins are newly identified steroid-like compounds from Taiwan's endemic medicinal mushrooms
and
. Scientific studies of the past two decades confirmed that antcins have various pharmacological ...activities, including potent anti-oxidant and anti-inflammatory effects. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease-2019 (COVID-19) pandemic and is characterized as a significant threat to global public health. It was recently identified that SARS-CoV-2 required angiotensin converting enzyme 2 (ACE2), a receptor which supports host cell entry and disease onset. Here, we report a novel function of antcins, in which antcins exhibit inhibitory effects on ACE2. Compared to the untreated control group, treatment with various antcins (antcin-A, antcin-B, antcin-C, antcin-H, antcin-I, and antcin-M) significantly inhibited ACE2 activity in cultured human epithelial cells. Indeed, among the investigated antcins, antcin-A, antcin-B, antcin-C, and antcin-I showed a pronounceable inhibition against ACE2. These findings suggest that antcins could be novel anti-ACE2 agents to prevent SARS-CoV-2 host cell entry and the following disease onset.
The cytostatic drug from natural products has acted as a chemotherapeutic agent used in treatment of a wide variety of cancers. Apigenin, a type of flavonoid, exhibits anticancer actions, but there ...is no report to show that apigenin induced apoptosis in osteosarcoma cells. The aim of this study was to investigate the effects of apigenin on U-2 OS human osteosarcoma cells and clarify that the apigenin-induced apoptosis-associated signals. The cytotoxic effects of apigenin were examined by culturing U-2 OS cells with or without apigenin. The percentage of viable cells via PI staining, apoptotic cells, productions of ROS and Ca2+, and the level of mitochondrial membrane potential (ΔΨm) were assayed by flow cytometry. The levels of apoptosis-related proteins were measured by immunoblotting. Results indicated that apigenin significantly decreased cell viability. Apigenin effectively induced apoptosis through the activations of caspase-3, -8, -9, and BAX and promoted the release of AIF in U-2 OS cells. In nude mice bearing U-2 OS xenograft tumors, apigenin inhibited tumor growth. In conclusion, apigenin has anticancer properties for induction of cell apoptosis in U-2 OS cells and suppresses the xenograft tumor growth. These findings offer novel information that apigenin possibly possesses anticancer activity in human osteosarcoma.
Small ubiquitin‐like modifier (SUMO) conjugation, or SUMOylation, is a reversible post‐translational modification that is important for regulation of many cellular processes including cell division ...cycle in the eukaryotic kingdom. However, only a portion of the components of the Chlamydomonas SUMOylation system are known and their functions and regulation investigated. The present studies are aimed at extending discovery and characterization of new components and improving the annotation and nomenclature of all known proteins and genes involved in the system. Even though only one copy of the heterodimerized SUMO‐activating enzyme, SAE1 and SAE2, was identified, the number of SUMO‐conjugating enzymes (SCEs) and SUMO proteases/isopeptidase was expanded in Chlamydomonas. Using the reconstituted SUMOylation system, we showed that SCE1, SCE2, and SCE3 have SUMO‐conjugating activity. In addition to SUMOylation, components required for other post‐translational modifications such as NEDDylation, URMylation, and UFMylation, were confirmed to be present in Chlamydomonas. Our data also showed that besides isopeptidase activity, the SUMO protease domain of SUPPRESSOR OF MAT3 7/SENTRIN‐SPECIFIC PROTEASE 1 (SMT7/SENP1) has endopeptidase activity that is capable of processing SUMO precursors. Moreover, the key cell cycle regulators of Chlamydomonas E2F1, DP1, CDKG1, CYCD2, and CYCD3 were SUMOylated in vitro, suggesting SUMOylation may be part of regulatory pathway modulating cell cycle regulators.
The number of people with metabolic syndrome (MetS) is increasing year by year, and MetS is associated with gut microbiota dysbiosis. The demand for health supplements to treat or prevent MetS is ...also growing.
Kaneh (CO) and
(TC) are endemic to Taiwan. Both have been shown to improve the symptoms of MetS, such as dyslipidemia and hyperglycemia. Herein, we investigated the effect of CO, TC and their formulations on diet-induced obese mice. Male C57BL/6J mice were fed with a high-fat diet (HFD) for 10 weeks to induce MetS. After that, the mice were fed with HFD supplemented with CO, TC, and various CO/TC formulations, respectively, for 14 weeks. The changes in physiological parameters and the composition of the gut microbiome were investigated. The results indicated that CO, TC, and their formulations effectively reduced hyperglycemia, and tended to alleviate MetS in obese mice. Moreover, we also observed that CO, TC, and their formulations improved gut microbiota dysbiosis by decreasing the Firmicutes-to-Bacteroidetes ratio and increasing the abundance of
spp. Our results revealed that CO and TC might have potential for use as a prebiotic dietary supplement to ameliorate obesity-related metabolic disorders and gut dysbiosis.
The objective of this study was to investigate the effects of tetrandrine (TET) on cell migration and invasion of nasopharyngeal carcinoma NPC‐TW 039 cells in vitro. TET at 1–10 μM did not change ...cell morphology and also did not decrease the total cell viability and proliferation in NPC‐TW 039 cells. It decreased the cell mobility based on decreased wound closure in NPC‐TW 039 cells by wound healing assay. TET suppressed the cell migration and invasion using transwell system. TET reduced MMP‐2 activities at 1–10 μM and these effects are in dose‐dependently. After exposed to various treatments, TET decreased the levels of p‐ERK, p‐JNK, p‐p38, RhoA, and NF‐κB at 48 hr. Based on these findings, we may suggest TET‐inhibited cell migration and invasion of NPC‐TW 039 cells via the suppression of MAPK and RhoA signaling pathways for inhibiting the MMP‐2 and ‐9 expression in vitro.
Practical applications
Tetrandrine (TET), a bis‐benzylisoquinoline alkaloid, is obtained from the dried root of Stephania tetrandra. TET has been shown to induce cancer cell apoptosis on human cancer cells but its anti‐metastasis effect on cell migration and invasion of nasopharyngeal carcinoma cells has not been investigated. Our results showed that TET significantly repressed the cell mobility, migration, and invasion of NPC‐TW 039 cells in vitro that involved in inhibiting RhoA, Ras accompanying with p38/MAPK signaling pathway. We conclude that TET may be the anticancer agents for nasopharyngeal carcinoma therapy in the future.
Tetrandrine (TET), a bis‐benzylisoquinoline alkaloid, is obtained from the dried root of Stephania tetrandra. TET significantly repressed the cell mobility, migration and invasion of NPC‐TW 039 cells in vitro that involved in inhibiting RhoA, Ras accompanying with p38/MAPK signaling pathway. We conclude that TET may be the anticancer agents for nasopharyngeal carcinoma therapy in the future.
Taiwanofungus camphoratus is a precious medicinal fungus endemic to Taiwan and has been used as traditional medicine for a long time. Many pharmacological studies have revealed that T. camphoratus ...possessed various biological activities, such as immunomodulatory effects, anticancer activity and liver protective function. The aim of this study is to investigate the non-specific and antigen (ovalbumin OVA)-specific immunomodulation effects of solid-state cultivated powder of T. camphoratus (Leader Antrodia cinnamomea LAC) in BABL/c male mice. In non-specific and antigen-specific immune function studies, 8-week-old mice were orally administered with LAC for 6 and 8 weeks, respectively. The results have shown that the proliferation of splenic immune cells, phagocytic activity of macrophages and cytolytic activity of natural killer cells were enhanced by LAC. Additionally, LAC increased the levels of IL-2, TNF-α, INF-γ, GM-CSF and serum OVA-IgG and OVA-IgM. These findings provided evidences that LAC had the immunomodulation effects on both antigen-specific and non-specific immune responses in mice.
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