Anticancer Activity of Neosetophomone B, An Aquatic Fungal Secondary Metabolite, Against Hematological Malignancie S

Cancer is one of the most life threatening diseases, causing nearly 13% death in the worldwide. Leukemia, cancer of the hematopoetic cells is the main cause of cancer death in adults and children. Therapeutic agents used in treatment of cancer are known to have narrow therapeutic window and tendency to develop resistance against some cancer cell lines thus, proposing a need to discover some novel agents to treat cancer. In the present study we investigated the anticancer activity of Neosetophomone B(NSP-B), an aquatic fungal metabolite isolated from Neosetophoma sp against leukemic cells (K562 and U937). MTT results demonstrated a dose dependent inhibition of cell proliferation in K562 and U937 cell lines. Annexin staining using flow cytometry indicated that NSP-B treatment cause a dose dependent apoptosis in leukemic cells.Western blot analysis showed that NSP-B mediated apoptosis involves sequential activation of caspase 9, 3 and poly (ADP-ribose) polymerase (PARP) cleavage. Furthermore NSP-B treatment of leukemic cells resulted in upregulation of pro-apoptotic proteins (Bax) with downregulation of anti-apoptotic proteins ( Bcl-2 ).Thus, present study focuses on exploring the mechanism of anticancer activity of NSP-B on leukemic cells, raising the possibility of its use as a novel therapeutic agent for hematological malignancies. Results: We sought to determine whether NSP-B suppresses the growth of leukemic cell lines. We tested a panel of leukemic cell lines with different doses of NSP-B. Cell viability decreased in a concentration-dependent manner in K562 and U937 cell lines. NSP-B induced apoptosis in K562 and U937 cell lines via downregulation of anti-apoptotic proteins and enhancement of pro-apoptotic proteins. NSP-B induced the activation of caspase cascade signaling pathway. Altogether our results suggest that the NSP-B plays an important role in apoptosis in leukemic cell lines .Conclusions: Our data provides insight on anticancer activities of NSP-B in leukemic cell lines (K562 and U937). NSP-B inhibit cell viability via inducing apoptosis. The NSP-B mediated apoptosis occurs via downregulation of anti-apoptotic proteins and enhancement of pro-apototic proteins, thereby activating the caspase-cascade signaling. Further studies are required to elicit role of NSP-B in regulating molecular pathway involved in the progression of cancer. Taken together, above results suggest that NSP-B may have a future therapeutic role in leukemia and possibly other hematological malignancies.

Stattic alleviates acute hepatic damage induced by LPS/d-galactosamine in mice

Increasing evidence indicates that signal transducer and activator of transcription 3 (STAT3), a vital transcription factor, plays crucial roles in the regulation of inflammation. STAT3 has become a novel therapeutic target for intervention in inflammation-related disorders. However, it remains unclear whether STAT3 plays a part in acute hepatic damage. To investigate the effects of STAT3 here, LPS/d-GalN-induced hepatic damage was induced in mice, the STAT3 inhibitor Stattic was administered, and the degree of liver injury, inflammation, and hepatocyte apoptosis were investigated. The results showed that Stattic mitigated the hepatic morphologic abnormalities and decreased the level of aminotransferase in LPS/D-GalN-insulted mice. The results also indicated that Stattic decreased the levels of TNF-α and IL-6, prevented the activation of the caspase cascade, suppressed cleavage of PARP, and decreased the quantity of TUNEL-positive cells. These results suggest that Stattic provided protective benefits in LPS/d-GalN-induced hepatic damage, and the protective effects might be associated with its anti-inflammatory and anti-apoptotic effects. Therefore, STAT3 might become a novel target for intervening in inflammation-based and apoptosis-based hepatic disorders.

A Tropical Lichen, Dirinaria consimilis Selectively Induces Apoptosis in MCF-7 Cells through the Regulation of p53 and Caspase-Cascade Pathway

Background: Breast cancer is the most leading cause of death, with 49.9% of crude incidence rate and 12.9% of crude mortality rate. Natural resources have been extensively used throughout history for better and safer treatment against various diseases. Objectives: The present study was aimed to investigate the antioxidant and anticancer potential of a tropical lichen Dirinaria consimilis (DCME) and its phytochemical analysis. Methods: The DCME was preliminarily evaluated for ROS, and RNS scavenging potential. Furthermore, DCME was evaluated for in vitro anticancer activity through cell proliferation assay, cell cycle analysis, annexin V/PI staining, morphological analysis, and western blotting study. Finally, the HPLC and LC-MS analyses were done to identify probable bioactive compounds. Results: The in vitro antioxidant studies showed promising ROS, and RNS scavenging potential of DCME. Moreover, the in vitro antiproliferative study bared the cytotoxic nature of DCME towards MCF-7 (IC50 - 98.58 ± 6.82μg/mL) and non-toxic towards WI-38 (IC50 - 685.85 ± 19.51μg/mL). Furthermore, the flow-cytometric analysis revealed the increase in sub G1 population as well as early apoptotic populations dose-dependently. The results from confocal microscopy showed the DNA fragmentation in MCF-7 upon DCME treatment. Finally, the western blotting study revealed the induction of tumor suppressor protein, p53, which results in increasing the Bax/Bcl-2 ratio and activation of caspase-cascade pathways. Conclusion: The activation of caspase-3, -8, -9 and PARP degradation led us to conclude that DCME induces apoptosis in MCF-7 through both intrinsic and extrinsic mechanisms. The LC-MS analysis showed the presence of various bioactive compounds.

Extract of Juniperus indica Bertol Synergizes with Cisplatin to Inhibit Oral Cancer Cell Growth via Repression of Cell Cycle Progression and Activation of the Caspase Cascade

Oral cancer—a type of head and neck cancer—is estimated to be the fifth most common cancer in Taiwan. However, efficacious therapies for oral cancer are still lacking due to drug resistance and recurrence. Consequently, the identification of new anticancer agents for clinical treatment is needed. Juniperus indica Bertol is a plant of the Juniperus genus often used as a treatment in traditional medicine due to its anti-inflammatory, antibacterial and diuretic functions. The biofunctions of Juniperus indica Bertol including its anticancer potential, have not been fully explored. As a result, the aim of this research was to investigate the anticancer activity of Juniperus indica Bertol extract (JIB extract) and determine whether JIB extract has synergistic effects with cisplatin in oral cancer. These results are the first to demonstrate that JIB extract exhibits anticancer capacity and synergizes with cisplatin to treat oral cancer. Our findings indicate that JIB extract has a potential to develop anticancer agent and chemo therapeutic adjuvant for oral cancer.