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Cancer is an uncontrolled multiplication of cells. The desire efficacy and severe toxicity of current anticancer drugs urge exploring and investigating a better alternative to existing chemotherapeutics. Natural products of marine origin are excellent sources of potential new drugs of enhanced biological activities., Objectives: Thus, the cytotoxic effects along with investigating the mode of cell death exerted by fractions, AP-9, AP-THR, DS-8 and DS-9 fraction of Acanthaster planci, Diadema setosum sp., on the human cervical cancer cell line, HeLa., Methods: The cytotoxicity of fractions has determined by using an MTS assay. The early and late apoptosis was studied by using the High content Screening (HCS) instrument., Results: The four fractions produced effective cytotoxicity effects with IC50 values at 72hr of less than 20 μg/ml in the order of AP-9 > DS-9 > APTHR-9 > DS-8. The fraction s exhibited cytotoxicity via mediating apoptotic mode of cell death. The early apoptosis by exposure of phosphatidylserine to the outer leaflet of the plasma membrane and late apoptosis due to the presence of green stain (DNA fragmentation) in treated cells., Conclusion: The potent bioactive compounds might be responsible for inducing apoptosis in cancer cells and, thus, the potential to be a successful candidate for exploring upcoming chemotherapeutic drugs.

Objective: Liver cancer is one of the most common causes of cancer death, with reduced survival rates. The development of new chemotherapeutic agents is essential to find effective cytotoxic drugs that give minimum side effects to the surrounding healthy tissues. The main objective of the present study was to evaluate the cytotoxic effects and mechanism of cell death induced by the crude and diethyl ether extract of Xylocarpus mouccensis on the human hepatocellular carcinoma cell line., Methods: The cytotoxicity activity was measured using the MTS assay. The mode of cell death determined by the apoptosis study, DNA fragmentation analysis done by using the TUNEL system. The pathway study or mechanism of apoptosis observed by study caspases 8, 9, 3/7 Glo-caspases method., Results: In this study, the methanol extracts prepared from leaf Xylocarpus mouccensis leaf produced cytotoxicity effect with IC50 (72hr) < 30µg/ml. The IC50 value at 72 hours exerted by diethyl ether extract of Xylocarpus moluccensis leaf was 0.22 µg/ml, which was more cytotoxic than to that of crude methanol extract. The results obtained by the colorimetric TUNEL system suggest that methanol crude extract of Xylocarpus moluccensis (leaf), diethyl ether extract of Xylocarpus moluccensis (leaf) and methanol extract of Xylocarpus granatum (bark) induced DNA fragmentation in the HepG2 cell line. Besides, the caspase-Glo assay demonstrated that diethyl ether leaf extract of Xylocarpus moluccensis triggered apoptotic cell death via activation of caspases -8, and -3/7 However, no visible activation was noticed for caspase -9. Furthermore, TLC indicates the presence of potential metabolites in an extract of Xylocarpus moluccensis., Conclusion: Thus, the present study suggests the remarkable potential of active metabolites in the extract of Xylocarpus moluccensis as a future therapeutic agent for the treatment of cancer., .

Cancer is a complex multifactorial process, unchecked and abrupt division, and cell growth—conventional chemotherapy, along with radiotherapy, is used to treat breast cancer. Due to reduce efficacy and less survival rate, there is a particular need for the discovery of new active anticancer agents. Natural resources such as terrestrial/marine plants or organisms are a promising source for the generation of new therapeutics with improving efficacy. The screening of natural plant extracts and fractions, isolations of phytochemicals, and mechanistic study of those potential compounds play a remarkable role in the development of new therapeutic drugs with increased efficacy. Cancer is a multistage disease with complex signaling cascades. The initial study of screening whole extracts or fractions and later the isolation of secondary compounds and their mechanism of action study gives a clue of potential therapeutic agents for future drug development. The phytochemicals present in extracts/fractions produce remarkable effects due to synergistically targeting multiple signals. In this review, the molecular targets of extracts/ fractions and isolated compounds highlighted. The therapeutic agent's mechanistic targets in drug development focused involves; i) Induction of Apoptosis, ii) modulating cell cycle arrest, iii) Inhibition or suppression of invasion and metastasis and iv) various other pro-survival signaling pathways. The phytochemicals and their modified analogs identified as future potential candidates for anticancer chemotherapy. [ABSTRACT FROM AUTHOR]

Cancer is a complex mechanism involving a series of cellular events. The glycoproteins such as hyaluronan (HA) are a significant element of extracellular matrix (ECM), involve in the onset of cancer developmental process. The pivotal roles of HA in cancer progression depend on dysregulated expression in various cancer. HA, also gain attention due to consideration as a primary ligand of CD44 receptor. The CD44, complex transmembrane receptor protein, due to alternative splicing in the transcription process, various CD44 isoforms predominantly exist. The overexpression of distinct CD44 isoforms (CD44v) standard (CD44s) depends on the tumour type and stage. The receptor proteins, CD44 engage in a variety of biological processes, including cell growth, apoptosis, migration, and angiogenesis. HA-CD44 interaction trigger survival pathways that result in cell proliferation, invasion ultimately complex metastasis. The interaction and binding of ligand-receptor HA-CD44 regulate the downstream cytoskeleton pathways involve in cell survival or cell death. Thus, targeting HA, CD44 (variant and standard) isoform, and HA-CD44 binding consider as an attractive and useful approach towards cancer therapeutics. The use of various inhibitors of HA, hyaluronidases (HYALs), and utilizing targeted Nano-delivery of anticancer agents and antibodies against CD44, peptides gives promising results in vitro and in vivo. However, they are in clinical trials with favourable and unfavourable outcomes, which reflects the need for various modifications in targeting agents and a better understanding of potential targets in tumour progression pathways. [ABSTRACT FROM AUTHOR]

The bidentate N -(1-Alkylpyridin-4 (1H) -ylidene)amide (PYA) pro-ligands [H 2 L Bn ][Cl] 2 (2), and [H 2 L Me ][TfO] 2 (3) were prepared by simple alkylation reactions of the known compound, N,N -di(pyridin-4-yl)oxalamide (H 2 L, 1). The Pd(II) complexes, [Pd(L Bn) 2 ][Cl] 2 (4), [Pd(L Me) 2 ][Cl][TfO] (5), Pd(L Bn)Cl 2 (6) and Pd(L Me)Cl 2 (7) were synthesized through reactions between these pro-ligands and suitable Pd(II) substrates in the presence of base. The molecular structures of 3 and 6 were obtained by single crystal X-ray structure determinations. Studies of the experimental and computational DNA binding interactions of the compounds 1 – 7 revealed that overall 4 and 6 have the largest values for the binding parameters K b and ΔG b o. The results showed a good correlation with the steric and electronic parameters obtained by quantitative structure activity relationship (QSAR) studies. In-vitro cytotoxicity studies against four different cell lines showed that the human breast cancer cell lines MCF-7 , T47D and cervical cancer cell line HeLa had either higher or similar sensitivities towards 4 , 6 and 2 , respectively, compared to cisplatin. In general, the cytotoxicity of the compounds, represented by IC 50 values, decreased in the order 4 > 6 > 2 > 5 > 3 > 1 > 7 in cancer cell lines. Apoptosis contributed significantly to the cytotoxic effects of these anticancer agents as evaluated by apoptosis studies. [Display omitted] • New oxalamide-based bidentate pyridinium amidate (PYA) donor ligands synthesized. • Water soluble Pd(II) complexes of these PYA chelating ligands synthesized. • Experimental and computational binding of the new compounds to DNA studied. • The complexes have similar cytotoxicity as cisplatin against 3 cancer cells lines. • The complexes promote programmed cell death (apoptosis). [ABSTRACT FROM AUTHOR]