X-ray Dose-Enhancing Impact of Functionalized Au–Fe3O4 Nanoheterodimers on MCF-7 and A549 Multicellular Tumor Spheroids

Au-Fe3O4 nanoheterodimers (NHD) were functionalized with the natural and synthetic anticancer drugs caffeic acid (CA), quercetin (Q) and 5-fluorocytidine (5FC). Their X-radiation dose-enhancing potential and chemotherapeutic efficacy for bimodal cancer therapy were investigated by designing multicellular tumor spheroids (MCTS) to in vitro avascular tumor models. MCTS were grown from the breast cancer cell lines MCF-7, MDA-MB-231, and MCF-10A. The MCF-7, MDA-MB-231 and MCF-10A MCTS were incubated with NHD-CA, NHD-Q, or NHD-5FC and then exposed to fractionated X-radiation comprising either a single 10 Gy dose, 2 daily single 5 Gy doses or 5 daily single 2 Gy doses. The NHD-CA, NHD-Q, and NHD-5FC affected the growth of X-ray irradiated and non-irradiated MCTS in a different manner. The impact of the NHDs on the glycolytic metabolism due to oxygen deprivation inside MCTS was assessed by measuring lactate secretion and glucose uptake by the MCTS. The NHD-CA and NHD-Q were found to act as X-radiation dose agents in MCF-7 MCTS and MDA-MB-231 MCTS and served as radioprotector in MCF-10A MCTS. X-ray triggered release of CA and Q inhibited lactate secretion and thereupon disturbed glycolytic reprogramming, whereas 5FC exerted their cytotoxic effects on both, healthy and tumor cells, after their release into the cytosol.

Download Full-text

Structures, Chemical Conversions, and Cytotoxicity of Tricholopardins C and D, Two Tricholoma Triterpenoids from the Wild Mushroom Tricholoma pardinum

Natural Products and Bioprospecting ◽

10.1007/s13659-021-00297-x ◽

2021 ◽

Author(s):

Chen Shi ◽

Yue-Ling Peng ◽

Juan He ◽

Zheng-Hui Li ◽

Ji-Kai Liu ◽

...

Keyword(s):

Hela Cell ◽

Single Crystal ◽

Cell Lines ◽

Cell Apoptosis ◽

Spectroscopic Methods ◽

Wild Mushroom ◽

X Ray Diffraction ◽

X Ray ◽

Hela Cell Lines ◽

Mcf 7

AbstractTwo undescribed Tricholoma triterpenoids, namely tricholopardins C (1) and D (2), were isolated from the wild mushroom Tricholoma pardinum. Their structures with absolute configurations were elucidated by spectroscopic methods, as well as the single crystal X-ray diffraction. Compounds 1 and 2 were further obtained by chemical conversions from the known analogues. Compound 1 showed significant cytotoxicity to MCF-7 and Hela cell lines with IC50 values of 4.7 μM and 9.7 μM, respectively. Its mechanism of inducing MCF-7 cell apoptosis was studied briefly. Graphical Abstract

Download Full-text

Spatially resolved metabolomics combined with multicellular tumor spheroids to discover cancer tissue relevant metabolic signatures

Analytica Chimica Acta ◽

10.1016/j.aca.2021.338342 ◽

2021 ◽

Vol 1155 ◽

pp. 338342

Author(s):

Qingce Zang ◽

Chenglong Sun ◽

Xiaoping Chu ◽

Limei Li ◽

Wenqiang Gan ◽

...

Keyword(s):

Cancer Tissue ◽

Multicellular Tumor Spheroids ◽

Tumor Spheroids ◽

Spatially Resolved ◽

Metabolic Signatures

Download Full-text

Single cell organization and cell cycle characterization of DNA stained multicellular tumor spheroids

Scientific Reports ◽

10.1038/s41598-021-96288-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Karl Olofsson ◽

Valentina Carannante ◽

Madoka Takai ◽

Björn Önfelt ◽

Martin Wiklund

Keyword(s):

Cell Cycle ◽

Single Cell ◽

Drug Distribution ◽

In Vitro Models ◽

Biological Information ◽

Dimensional Structure ◽

Multicellular Tumor Spheroids ◽

Tumor Spheroids ◽

Nuclear Segmentation

AbstractMulticellular tumor spheroids (MCTSs) can serve as in vitro models for solid tumors and have become widely used in basic cancer research and drug screening applications. The major challenges when studying MCTSs by optical microscopy are imaging and analysis due to light scattering within the 3-dimensional structure. Herein, we used an ultrasound-based MCTS culture platform, where A498 renal carcinoma MCTSs were cultured, DAPI stained, optically cleared and imaged, to connect nuclear segmentation to biological information at the single cell level. We show that DNA-content analysis can be used to classify the cell cycle state as a function of position within the MCTSs. We also used nuclear volumetric characterization to show that cells were more densely organized and perpendicularly aligned to the MCTS radius in MCTSs cultured for 96 h compared to 24 h. The method presented herein can in principle be used with any stochiometric DNA staining protocol and nuclear segmentation strategy. Since it is based on a single counter stain a large part of the fluorescence spectrum is free for other probes, allowing measurements that correlate cell cycle state and nuclear organization with e.g., protein expression or drug distribution within MCTSs.

Download Full-text