Evaluation of the antiproliferative activity of 106 marine microbial metabolites against human lung cancer cells and potential antiproliferative mechanism of purpuride G.

A total of 106 marine microbial metabolites were evaluated for their antiproliferative activity against human lung cancer cells. Results showed that 23 compounds exhibited activity in inhibiting the proliferation of A549 and H157 cells with IC50 values ranging from 1.5 to 48.2 µM. Pyrrospirone F, chrysophanol, physcion, and purpuride G are the four most active compounds with IC50 values of 1.5-7.3 µM. Further investigation of purpuride G (a newly discovered sesquiterpene lactone) demonstrated its potent antiproliferative activity against six different lung cancer cells of A549, H157, H460, H1299, H1703, and PC9 with IC50 values of 2.1-3.3 µM. The antiproliferative activity of purpuride G against cancer cells is related to block cell cycle, induce apoptosis through regulating the apoptotic proteins Bcl-2 and Bax, and inhibit glycolysis by downregulating two key glycolytic enzymes of hexokinase 2 and pyruvate kinase M2.

Antiproliferative Activity and Potential Mechanism of Marine-Sourced Streptoglutarimide H against Lung Cancer Cells.

In 2019, streptoglutarimide H (SGH) was characterized as a new glutarimide from the secondary metabolites produced by a marine-derived actinomycete Streptomyces sp. ZZ741 and shown to have in vitro antiglioma activity. However, the antiproliferative activity and potential mechanism of SGH against lung cancer cells have not yet been characterized. This study demonstrated that SGH significantly inhibited the proliferation of different lung cancer cells. In terms of mechanism of action, SGH downregulated cell cycle- and nucleotide synthesis-related proteins to block cell cycle at G0/G1 phase, reduced the expression levels of glycolytic metabolic enzymes to inhibit glycolysis, and downregulated the important cancer transcription factor c-Myc and the therapeutic target deubiquitinase USP28. Potent anticancer activity and multiple mechanisms indicated SGH to be a novel antitumor compound against lung cancer cells.

Antileukemic effect of caffeic acid 3,4-dihydroxyphenetyl ester. Evidences for its mechanisms of action.

BACKGROUND: Caffeic acid 3,4-dihydroxyphenethyl ester (CADPE) is a natural polyphenolic ester isolated as a minor component from a water extract of the Chinese medicine Zhongjiefeng [Sarcandra glabra (Thunb.) Nakai (Chloranthaceae)] and has previously shown to have activity against solid tumors through the modulation of multiple targets or signal pathways. However, the activity and potential mechanism of CADPE against leukemia cells have not yet been characterized. PURPOSE: To investigate whether and how CADPE kills leukemia cells. METHOD: (1) The activity of CADPE inhibiting the growth of different leukemia cell lines was evaluated by MTT assay; (2) Cell cycle arrest and apoptosis induced by CADPE were determined by flow cytometry with FlowJo software for quantification; (3) The protein levels were analyzed by Western blot and ubiquitin-binding c-Myc was acquired by co-immunoprecipitation. RESULTS: CADPE exerted potent activity against different leukemia cell lines with low toxicity in normal cells. In terms of mechanism of action, CADPE promoted ubiquitin-proteasome-dependent degradation of c-Myc through activating glycogen synthase kinase-3ß (GSK3ß) and downregulating deubiquitinating enzyme USP28 to trigger the interaction of c-Myc with ubiquitin ligase Fbw7, resulting in the downregulation of cell cycle regulators and anti-apoptotic proteins and consequently, cell cycle arrest and cell apoptosis. CONCLUSION: CADPE is a novel c-Myc inhibitor with high activity and a unique mechanism for killing leukemia cells.

A small natural molecule CADPE kills residual colorectal cancer cells by inhibiting key transcription factors and translation initiation factors.

Residual disease is the major cause for colorectal cancer (CRC) relapse. Herein, we explore whether and how a natural molecule CADPE killed heterogenic populations in a panel of CRC cell lines with KRAS/BRAF mutations that are natively resistant to EGFR- or VEGFR-targeted therapy, without sparing persistent cells, a reservoir of the disease relapse. Results showed that CADPE killed the tumor bulk and residual cells in the panel of CRC cell lines, rapidly inactivated c-Myc, STAT3, and NF-κB, and then decreased the protein levels of key signaling molecules for CRC, such as ß-catenin, Notch1, and the nodes of mTOR pathways; eukaryotic translation initiation factors (eIF4F); anti-apoptotic proteins (Bcl-xl, Mcl-1, and survivin); and stemness-supporting molecules (CD133, Bim-1, and VEGF). In terms of mechanism of action, concurrent downregulation of Mcl-1, Bcl-xl, and survivin was necessary for CADPE to kill CRC bulk cells, while additional depletion of CD133 and VEGF proteins was required for killing the residual CRC cells. Moreover, the disabled c-Myc, STAT3, NF-κB, and eIF4F were associated with the broadly decreased levels of anti-apoptosis proteins and pro-stemness proteins. Consistently, CADPE suppressed CRC tumor growth associated with robust apoptosis and depleted levels of c-Myc, STAT3, NF-κB, eIF4F, anti-apoptotic proteins, and pro-stemness proteins. Our findings showed the promise of CADPE for treating CRC and suggested a rational polytherapy that disables c-Myc, STAT3, NF-κB, and eIF4F for killing CRC residual disease.

Blood donation and health status based on SF-36: The mediating effect of cognition in blood donation.

OBJECTIVE: The relationship among blood donation, cognition in blood donation and health condition of blood donors remains unclear. Based on our hypothesis, this study aimed to explore the mediating effect of cognition in blood donation on the relationship between blood donation and blood donors' health status. METHODS: A total of 837 participants who had prior experience in donating whole blood were recruited into a cross-sectional survey. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Questionnaire on Cognition in Non-remunerated Blood Donation were used to evaluate the health status and the level of cognition in blood donation, respectively. Blood donation referred to the cumulative times of blood donation. The mediating effect of cognition in blood donation was analyzed by applying a path model. RESULTS: The results revealed that blood donation was positively related to the physical component summary (PCS) and mental component summary (MCS) of SF-36, and cognition in blood donation was shown to have a partial mediating effect on the relationship between blood donation and both PCS and MCS. The effect size of cognition in blood donation was 24.63% in PCS and 26.72% in MCS. CONCLUSIONS: Blood donation is positively correlated with SF-36 outcomes (PCS and MCS) of blood donors, and cognition in blood donation plays a partial mediating effect in the relationship between blood donation and PCS and MCS.