Hexane partition from Annona crassiflora Mart. promotes cytotoxity and apoptosis on human cervical cancer cell lines.

Cervical cancer is the third most commonly diagnosed tumor type and the fourth cause of cancer-related death in females. Therapeutic options for cervical cancer patients remain very limited. Annona crassiflora Mart. is used in traditional medicine as antimicrobial and antineoplastic agent. However, little is known about its antitumoral properties. In this study the antineoplastic effect of crude extract and derived partitions from A. crassiflora Mart in cervical cancer cell lines was evaluated. The crude extract significantly alters cell viability of cervical cancer cell lines as well as proliferation and migration, and induces cell death in SiHa cells. Yet, the combination of the crude extract with cisplatin leads to antagonistic effect. Importantly, the hexane partition derived from the crude extract presented cytotoxic effect both in vitro and in vivo, and initiates cell responses, such as DNA damage (H2AX activity), apoptosis via intrinsic pathway (cleavage of caspase-9, caspase-3, poly (ADP-ribose) polymerase (PARP) and mitochondrial membrane depolarization) and decreased p21 expression by ubiquitin proteasome pathway. Concluding, this work shows that hexane partition triggers several biological responses such as DNA damage and apoptosis, by intrinsic pathways, and was also able to promote a direct decrease in tumor perimeter in vivo providing a basis for further investigation on its antineoplastic activity on cervical cancer.

Synthesis, spectroscopic, physicochemical and structural characterization of tetrandrine-based macrocycles functionalized with acridine and anthracene groups: DNA binding and anti-proliferative activity.

In this work, we report on the synthesis of two new mono-alkylated tetrandrine derivatives with acridine and anthracene units, MAcT and MAnT. The compounds were fully characterized by physicochemical techniques and single-crystal X-ray diffraction analysis. In addition, both derivatives were studied as nucleotide receptors and double-stranded DNA binders in aqueous phosphate buffer at pH = 7.2 using UV-vis and fluorescence spectroscopy. According to the molecular recognition studies, MAcT and MAnT exhibit high affinity (K ∼ 105 M-1) and selectivity for ds-DNA, presumably in an intercalation mode. Finally, the anti-proliferative effects of the tetrandrine derivatives on different cancer cell lines were explored, revealing promising activities. Particularly, the mono-anthracene tetrandrine derivative MAnT showed an IC50 of 2.74 µg/mL on the HeLa cervical cancer cell line, representing a value 3.3 times smaller than that obtained for unsubstituted tetrandrine. Examination of the cytotoxic effects on the HeLa cell line by inverted microscopy suggests that the cell death mechanism consists basically in apoptosis. The molecular modelling of three ds-DNA-MAcT complexes, suggested that the macrocycles may use an intercalation binding mode towards DNA. MAcT is predicted to bind into the major groove of the ds-DNA providing non-covalent interactions such as electrostatic, van der Waals and hydrophobic interactions that lead to selectivity. Overall experimental data supports the mode of action of MAnT and MAcT as cytotoxic compounds against cancer cell lines via a DNA interaction mechanism.

Zinc Oxide Flower-Like Nanostructures That Exhibit Enhanced Toxicology Effects in Cancer Cells.

Nanostructured zinc oxide (ZnO) materials have been intensively studied because of their potential applications in cancer therapies. However, a better comprehension of the toxicity of the flower-like ZnO nanostructures toward cancer cells is still needed. In this study, we investigate the cytotoxicity of a ZnO flower-like nanostructure produced at low temperature via aqueous solution in human cervical carcinoma (HeLa) cells and noncancerous cell-line murine fibroblast (L929) cells. Nanotoxicology effects were analyzed to study apoptosis and necrosis processes, reactive oxygen species production, and cellular uptake. Cells remained incubated for 24 h in concentrations of 0.1, 1.0, and 10.0 µg mL-1 ZnO nanoparticles (NPs), with the estimated rods length varying from 1.7 ± 0.4 to 2.3 ± 0.4 µm, synthesized at different times (4, 2, and 0.5 h) by an aqueous solution method. The cytotoxic response observed in noncancerous and cancer cells showed that all of the ZnO NPs synthesized by an aqueous solution exhibited enhanced toxicology effects in cancer cells. ZnO flower-nanostructures exhibited a higher cytotoxic against cancer HeLa cells, in comparison to the noncancerous cell line L929. The cytotoxic response of ZnO NPs at 0.5, 2, and 4 h in L929 cells was not statistically significant. This ability may be of clinical interest because of the effectiveness of ZnO NPs to distinguish between normal and cancer cells in cancer therapy.