Caspase Cascade Activation During Apoptotic Cell Death of Human Lung Carcinoma Cells A549 Induced by Marine Sponge Callyspongia aerizusa.

INTRODUCTION: In this study, Callyspongia aerizusa (CA), one of the most popular marine sponges for cancer therapy research, was investigated for its phytochemical compounds and evaluated for its anticancer activity in various cell lines. Since lung cancer is the most frequently diagnosed cancer, a solution from this marine source is a good choice to address the resistance to anticancer agents. Elucidation of the underlying mechanism of cell death elicited by a CA extract in human lung carcinoma cells A549 was undertaken. METHODS: The presence of secondary metabolites in CA methanol extract was revealed by gas chromatography-mass spectrometry (GC-MS) and evaluated on four cancerous cell lines and a non-cancerous cell line using Cell Counting Kit-8. Since the activity of CA extract in A549 cells was then evaluated through clonogenic assay, morphological detection of apoptosis, polymerase chain reaction (PCR) and Western blot assay, were also presented in this study. RESULTS: GC-MS analysis revealed the presence of two ergosteroids, ergost-22-en-3-one, (5ß,22E), and ergost-7-en-3-ol, (35ß) in the sponge extract that was suggested to suppress A549 cells (IC50 9.38 µg/mL), and another cancerous cell's viability (IC50 3.12-10.72 µg/mL) in 24 h, but not in the non-cancerous cells. Moreover, CA extract was also able to reduce the colony-forming ability of A549 cells, and through A549 cells morphology seems that apoptosis is the underlying mechanism of cell death. Further, the treatment with CA extract induced the up-regulation of caspase-9, caspase-3, and PARP-1, and the down-regulation of BCL-2, in both mRNA and proteins expression level, promoting apoptotic cell death via caspase cascade. CONCLUSION: These findings suggest that the compounds in CA extract possess the ability to induce apoptotic cell death in A549 cells and could become a promising candidate for future anticancer therapy.

Briarane diterpenes from two species of octocorals, Ellisella sp. and Pteroeides sp.

Eight new briarane diterpenes (1-4, 7-10) have been isolated from two species of octocorals and the structures elucidated by spectroscopic analysis. Two diterpenes (2, 3) from the gorgonian Ellisella sp. inhibited cytokinesis, causing multinuclei formation on NBT-II cells, while a known briarane (12) from the sea pen Pteroeides sp. showed reversal of multidrug resistance.

Sesquiterpene aminoquinones, from a marine sponge, induce erythroid differentiation in human chronic myelogenous leukemia, K562 cells.

A new sesquiterpene aminoquinone, 5-epi-smenospongorine, together with nine known sesquiterpene quinone/phenols, was isolated as differentiation-inducing substances to K562 cells into erythroblast from the marine sponge Dactylospongia elegans. The structure-activity relationship study of these compounds clarified that the quinone skeleton is indispensable and the amino group plays an important role for their differentiation-inducing activity to K562 cells into erythroblast.

Pyridoacridine alkaloids inducing neuronal differentiation in a neuroblastoma cell line, from marine sponge Biemna fortis.

A new and three known pyridoacridine alkaloids were isolated from the Indonesian marine sponge Biemna fortis as neuronal differentiation inducers against a murine neuroblastoma cell line, Neuro 2A. The chemical structure of the new compound, labuanine A (1), was determined by spectroscopic study and chemical conversion. These pyridoacridine alkaloids induced multipolar neuritogenesis in more than 50% of cells at 0.03-3 micro M concentration. Compound 3, which showed the strongest neuritogenic activity among them, also induced increase of acetylcholinesterase, a neuronal marker in Neuro 2A and arrested cell cycle at the G2/M phase.

Bitungolides A-F, new polyketides from the Indonesian sponge Theonella cf. swinhoei.

Six new polyketides, bitungolides A-F (1-6), have been isolated from the Indonesian sponge Theonella cf. swinhoei and their structures elucidated by spectroscopic data and X-ray diffraction analysis. The bitungolides are a new class of Theonella metabolites that inhibit dual-specificity phosphatase VHR.

Lembehsterols A and B, novel sulfated sterols inhibiting thymidine phosphorylase, from the marine sponge Petrosia strongylata.

Lembehsterols A (1) and B (2), two novel sulfated sterols, were isolated from the marine sponge Petrosia strongylata. Both sterols showed inhibitory activity against thymidine phosphorylase, which is an enzyme related to angiogenesis in solid tumors. The structures of these sulfated sterols were established on the basis of chemical and physicochemical evidence.