Massive induction of apoptosis of multicellular tumor spheroids by a novel compound with a calmodulin inhibitor-like mechanism

Mohanty, Chitralekha; Fayad, Walid; Olofsson, Maria Hägg; Larsson, Rolf; Milito, Angelo De; Fryknäs, Mårten; Linder, Stig

doi:10.7243/2049-7962-2-19

Cited by 5 publications

(9 citation statements)

References 38 publications

(43 reference statements)

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“…However, they observed a fraction of quiescent cells, located in spheroid cores, that were resistant to NSC647889-induced apoptosis. These data suggest that cells in hypoxic and nutrientlimited areas are resistant to apoptosis and die for other mechanisms (Mohanty et al, 2013). Weiswald et al (2009) proposed an original study in which they spontaneously obtained a 3D culture model, called colonosphere, from specimens subjected to mechanical dissociation.…”

Section: Scaffold-free 3d Culture Systemsmentioning

confidence: 99%

Preclinical three‐dimensional colorectal cancer model: The next generation of in vitro drug efficacy evaluation

Sensi

D’Angelo

DaRonco

et al. 2018

Journal Cellular Physiology

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Colorectal cancer (CRC), the third most common cancer diagnosed in both men and women in the United States, shows a highly ineffective therapeutic management. In these years neither substantial improvements nor new therapeutic approaches have been provided to patients. Performing the early lead discovery phases of new cancer drugs in cellular models, resembling as far as possible the real in vivo tumor environment, may be more effective in predicting their future success in the later clinical phases. In this review, we critically describe the most representative bioengineered models for anticancer drug screening in CRC from the conventional two‐dimensional models to the new‐generation three‐dimensional scaffold‐based ones. The scaffold aims to replace the extracellular matrix, thus influencing the biomechanical, biochemical, and biological properties of cells and tissues. In this scenario, we believe that reconstitution of tumor condition is mandatory for an alternative in vitro methods to study cancer development and therapeutic strategies.

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Section: Scaffold-free 3d Culture Systemsmentioning

confidence: 99%

Preclinical three‐dimensional colorectal cancer model: The next generation of in vitro drug efficacy evaluation

Sensi

D’Angelo

DaRonco

et al. 2018

Journal Cellular Physiology

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“…A recent study by Mohanty and his team has demonstrated the potential of HCT-116 colon carcinoma cells grown as spheroids with 500 μm of diameter to unravel novel chemotherapeutic drugs [48]. Using this model, it was evidenced a potent apoptotic effect of a new small molecule (NSC647889).…”

Section: Colorectal Cancermentioning

confidence: 98%

“…For instance, murine dermis is thin and comprises typically 3 layers of epidermis, while human possesses a thick dermis and between 6 and 10 layers of epidermis. For all these reasons, Significant morphologic differences; changes in gene expression patterns that was in line with the sensitivity to anti-EGFR targeted therapy [47] spheroids cisplatin, melphalan and vinblastine, NSC647889 Novel drugs that show considerably stronger cytotoxic activity in 3-D culture compared to standard agents can be identified [48] Bioreactor and 3D collagen scaffold 5-Fluorouracil, ABT-199 (BCL-2 inhibitor) BCL-2 inhibitor ABT-199 induced cytotoxic effects in p3D but not in 2D cultures [49] Ex vivo colospheres…”

Section: Melanomamentioning

confidence: 99%

“…Using this model, it was evidenced a potent apoptotic effect of a new small molecule (NSC647889). Furthermore, mechanistic insights could be obtained, since resistance to treatment was observed at the inner core of the spheroids, suggesting that hypoxia and nutrient availability may limit the efficacy of the drug in an in vivo microenvironment [48].…”

Section: Colorectal Cancermentioning

confidence: 99%

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Anti-Cancer Drug Validation: the Contribution of Tissue Engineered Models

Carvalho

Lima

Reis

et al. 2017

Stem Cell Rev and Rep

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Drug toxicity frequently goes concealed until clinical trials stage, which is the most challenging, dangerous and expensive stage of drug development. Both the cultures of cancer cells in traditional 2D assays and animal studies have limitations that cannot ever be unraveled by improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. Considering the NCI60, a panel of 60 cancer cell lines representative of 9 different cancer types: leukemia, lung, colorectal, central nervous system (CNS), melanoma, ovarian, renal, prostate and breast, we propose to review current "state of art" on the 9 cancer types specifically addressing the 3D tissue models that have been developed and used in drug discovery processes as an alternative to complement their study.

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“…Results indicated that the cells in different tumor microregions respond differently to the chemotherapeutic drugs due to their complex ultrastructural organization. Further, Mohanty et al tested a chemical library of compounds for establishing high-throughput drug screening on a 3D colon cancer model (HCT-116). According to their observation, the most potent antineoplastic compound also failed to kill the quiescent cells residing at the tumor core.…”

Section: Different 3d Models For Tumor Studiesmentioning

confidence: 99%

3D Bioprinting of Tumor Models for Cancer Research

Kang

Datta

Shanmughapriya

et al. 2020

ACS Appl. Bio Mater.

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The exact mechanistic understanding of cancer metastasis continues to be unknown, although it is a major cause of death worldwide. Along with the tumor mass, the tumor microenvironment also contributes to pathogenesis and treatment resistance. Tumors are characterized by a high degree of heterogeneity and complexity. However, the fabrication of suitable in vitro models of the microenvironment is difficult as two-dimensional (2D) models do not completely recapitulate the biochemical and biophysical signals of the tumor environment. Thus, three-dimensional (3D) tumor models are emerging as vital tools for the comprehensive understanding of the sophisticated disease. Among different 3D models such as spheroid cultures, biopolymer scaffolds, organ on chip, and ex vivo tissue slices, 3D bioprinting has a competitive advantage due to the ability to precisely control and define the desired structure and position of multiple types of cells in a high-throughput manner. In this Review, we discussed the 3D bioprinted tumor models that integrate their microenvironment with different cell types, substrates, and bioprinting modalities and their application in drug screening and therapy. Finally, we highlighted the comprehensive understanding of the cancer microenvironment by 3D printed tumor models that are more physiologically relevant than the other models and expounded the challenges that need to be addressed for the clinical translation.

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Massive induction of apoptosis of multicellular tumor spheroids by a novel compound with a calmodulin inhibitor-like mechanism

Cited by 5 publications

References 38 publications

Preclinical three‐dimensional colorectal cancer model: The next generation of in vitro drug efficacy evaluation

Preclinical three‐dimensional colorectal cancer model: The next generation of in vitro drug efficacy evaluation

Anti-Cancer Drug Validation: the Contribution of Tissue Engineered Models

3D Bioprinting of Tumor Models for Cancer Research

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