Deoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber, showed inhibition of the growth of various tumor cells in vitro. In the present study, we investigated the cytotoxicity and apoptosis-inducing capacity of deoxyelephantopin on lung adenocarcinoma (A549) cells. The cytotoxic effect of deoxyelephantopin on A549 cells and normal lymphocytes was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 50% inhibitory concentration (IC50) value was determined. The self-renewal and proliferating potential of A549 cells after treatment with deoxyelephantopin were examined by colony formation assay. Cellular morphology of deoxyelephantopin-treated cells was observed using phase-contrast microscopy. The induction of apoptosis was evaluated using acridine orange and ethidium bromide staining, Hoechst 33342 staining, terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labeling (TUNEL) assay, DNA fragmentation analysis and Annexin V-fluorescein isothiocyanate staining by flow cytometry. Activation of caspases was detected using fluorogenic substrate specific to caspases 2, 3, 8 and 9 and flow cytometric analysis. The total cellular DNA content and expression of cleaved poly (ADP-ribose) polymerase was also analyzed. Deoxyelephantopin exhibited cytotoxicity to A549 cells (IC50 = 12.287 μg/mL), however, there was no toxicity towards normal human lymphocytes. Deoxyelephantopin suppressed the colony-forming ability of A549 cells in a dose-dependent manner. Acridine orange, ethidium bromide and Hoechst 33342 staining showed cell shrinkage, chromosomal condensation and nuclear fragmentation, indicating induction of apoptosis. Deoxyelephantopin increased apoptosis of A549 cells, as evidenced by more TUNEL-positive cells. DNA fragmentation and Annexin V staining revealed late-stage apoptotic cell population. Deoxyelephantopin inhibited A549 cell growth by cell cycle arrest at G2/M phase and induced apoptosis through both extrinsic and intrinsic pathways. These results suggest that deoxyelephantopin has great potential as a new chemotherapeutic agent to be developed further for the treatment of lung cancer.

Deoxyelephantopin (DOE) is a natural bioactive sesquiterpene lactone from Elephantopus scaber, a traditionally relevant herb in Chinese and Indian medicine. It has shown promising anticancer effects against a broad spectrum of cancers. We examined the effect of DOE on growth, autophagy, apoptosis, cell cycle progression, metastasis, and various molecular signaling pathways in cancer cells, and endeavored to decipher the molecular mechanisms underlying its effect. The cytotoxicity of DOE was examined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and colony formation assays. The antimetastatic potential of DOE was identified by wound closure, as well as invasion and migration assays. The expression of mRNAs and proteins related to cytotoxicity in cancer cells induced by DOE was investigated using reverse transcription-polymerase chain reaction, flow cytometry, and Western blot analysis. DOE showed significant cytotoxicity and induced apoptosis in cancer cells. DOE promoted the autophagy of HCT 116 and K562 cells. DOE arrested cell cycle progression in the G2/M phase. DOE treatment caused activation of caspase-8, -9, -3 and -7, reactive oxygen species production, and cleavage of cleavage of poly-ADP-ribose polymerase (PARP), the markers of apoptosis. Moreover, apoptosis induction was associated with mitochondrial permeability and endoplasmic reticulum stress. Treatment of cancer cells with DOE inhibited mitogen-activated protein kinases, nuclear factor-kappa B, phosphatidylinositol 3-kinase (PI3K/Akt), and β-catenin signaling. Furthermore, treatment of DOE increased the expression of p53, phospho-Jun amino-terminal kinases (p-JNK), and p-p38 and decreased the expression of phospho-signal transducer and activator of transcription 3 (p-STAT3) and phospho-mammalian target of rapamycin (p-mTOR) in cancer cells. DOE downregulated matrix metalloproteinase (MMP-2) and MMP-9, urokinase-type plasminogen activator (uPA), and urokinase-type plasminogen activator receptor (uPAR) mRNA levels in cancer cells. These findings concluded that DOE may be useful as a chemotherapeutic agent against cancer.

Marine fungi, one of the major decomposers of marine environment, is found to produce potential enzymes and novel biomolecules. The present study explored bioprospecting potentials such as antimicrobial, anticancer and enzymatic activities of marine sediment-derived fungi isolated from continental slope of Eastern Arabian Sea. Morphology and ITS sequencing identified the fungus as Penicillium sp. ArCSPf. The fungal strain exhibited amylase, gelatinase, phytase, lipase and pectinase activity. The active fraction obtained from the ethyl acetate extract column fractionation (F2) of fungus showed antibacterial activity against both methicillin-resistant Staphylococcus aureus (MRSA) and Bacillus cereus. Minimum inhibitory concentrations of F2 were 125 μg/mL for MRSA and 62.5 μg/mL for B. cereus. The active fraction showed a significant anticancer activity (IC₅₀ = 22.79 µg/mL) against MCF-7 breast cancer cells. The secondary metabolite (Z)-Octadec-9-enamide (oleamide, m/z 282.27 (M + H⁺)] was identified in the LC-MS/MS analysis of active fraction F2 in positive ionisation mode. To the best of our knowledge, this is the first report on exploring the bioprospecting potential of a sediment-derived fungus from continental slope of eastern Arabian Sea for the production of therapeutically active compounds.

A marine bacterial isolate, Bacillus vietnamensis sp. MSB17 from the sediments collected from the continental slope of the eastern Arabian Sea exhibited good Malachite Green (MG) decolorization ability in mineral medium supplemented with glucose and yeast extract under static conditions. The complete decolorization of dye (50 mg/L) was attained within 4 h of incubation. The activities of enzymes such as tyrosinase (0.62 IU/ml), laccase (12.02 U/ml), and manganese peroxidase (6.23 U/ml) were observed during dye degradation. UV-VIS, FT-IR, and GC-MS analysis of dye samples extracted with ethyl acetate confirmed the biodegradation of MG into methanone, [4-(dimethylamino) phenyl] phenyl- and 2, 6-bis (1, 1-dimethylethyl) phenol. The metabolites obtained from B. vietnamensis sp. MSB17 mediated MG degradation did not exhibit any microbial toxicity and phytotoxicity. The present study indicated the efficiency of Bacillus vietnamensis sp. MSB17 to effectively degrade MG, revealing its potential to be further utilized for bioremediation purposes.