Drug-adapted cancer cell lines as preclinical models of acquired resistance

Michaelis, Martin; Wass, Mark N.; Činátl, Jindřich

doi:10.20517/cdr.2019.005

Cited by 22 publications

(38 citation statements)

References 124 publications

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“…Prostate cancer cell lines PC3, DU145, LNCaP, and 22Rv1 were obtained from the German Collection of Microorganisms and Cell Cultures (DSMZ). The DX-resistant sublines were derived from the Resistant Cancer Cell Line (RCCL) collection ( ) [ 73 ]. LNCaP cells were grown and subcultured in Iscove Basal medium (Biochrom GmbH, Berlin, Germany), and PC3, DU145, and 22Rv1 cells were grown in RPMI-1640 medium (Gibco, Thermo Fisher Scientific, Darmstadt, Germany).…”

Section: Methodsmentioning

confidence: 99%

Shikonin Reduces Growth of Docetaxel-Resistant Prostate Cancer Cells Mainly through Necroptosis

Markowitsch

Juetter

Schupp

et al. 2021

Cancers

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The prognosis for advanced prostate carcinoma (PCa) remains poor due to development of therapy resistance, and new treatment options are needed. Shikonin (SHI) from Traditional Chinese Medicine has induced antitumor effects in diverse tumor entities, but data related to PCa are scarce. Therefore, the parental (=sensitive) and docetaxel (DX)-resistant PCa cell lines, PC3, DU145, LNCaP, and 22Rv1 were exposed to SHI [0.1–1.5 μM], and tumor cell growth, proliferation, cell cycling, cell death (apoptosis, necrosis, and necroptosis), and metabolic activity were evaluated. Correspondingly, the expression of regulating proteins was assessed. Exposure to SHI time- and dose-dependently inhibited tumor cell growth and proliferation in parental and DX-resistant PCa cells, accompanied by cell cycle arrest in the G2/M or S phase and modulation of cell cycle regulating proteins. SHI induced apoptosis and more dominantly necroptosis in both parental and DX-resistant PCa cells. This was shown by enhanced pRIP1 and pRIP3 expression and returned growth if applying the necroptosis inhibitor necrostatin-1. No SHI-induced alteration in metabolic activity of the PCa cells was detected. The significant antitumor effects induced by SHI to parental and DX-resistant PCa cells make the addition of SHI to standard therapy a promising treatment strategy for patients with advanced PCa.

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Section: Methodsmentioning

confidence: 99%

Shikonin Reduces Growth of Docetaxel-Resistant Prostate Cancer Cells Mainly through Necroptosis

Markowitsch

Juetter

Schupp

et al. 2021

Cancers

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“…The cell lines RT4, RT112, T24, and TCCSup were obtained from DSMZ. The cisplatin-resistant sublines were derived from the RCCL collection ( ) [ 37 ]. RT4 (grade 1), RT112 (grade 2/3), T24 (grade 3), and TCCSup (grade 4) represent transitional cell carcinomas.…”

Section: Methodsmentioning

confidence: 99%

Artesunate Impairs Growth in Cisplatin-Resistant Bladder Cancer Cells by Cell Cycle Arrest, Apoptosis and Autophagy Induction

Zhao¹,

Vakhrusheva²,

Markowitsch³

et al. 2020

Cells

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Cisplatin, which induces DNA damage, is standard chemotherapy for advanced bladder cancer (BCa). However, efficacy is limited due to resistance development. Since artesunate (ART), a derivative of artemisinin originating from Traditional Chinese Medicine, has been shown to exhibit anti-tumor activity, and to inhibit DNA damage repair, the impact of artesunate on cisplatin-resistant BCa was evaluated. Cisplatin-sensitive (parental) and cisplatin-resistant BCa cells, RT4, RT112, T24, and TCCSup, were treated with ART (1–100 µM). Cell growth, proliferation, and cell cycle phases were investigated, as were apoptosis, necrosis, ferroptosis, autophagy, metabolic activity, and protein expression. Exposure to ART induced a time- and dose-dependent significant inhibition of tumor cell growth and proliferation of parental and cisplatin-resistant BCa cells. This inhibition was accompanied by a G0/G1 phase arrest and modulation of cell cycle regulating proteins. ART induced apoptos is by enhancing DNA damage, especially in the resistant cells. ART did not induce ferroptosis, but led to a disturbance of mitochondrial respiration and ATP generation. This impairment correlated with autophagy accompanied by a decrease in LC3B-I and an increase in LC3B-II. Since ART significantly inhibits proliferative and metabolic aspects of cisplatin-sensitive and cisplatin-resistant BCa cells, it may hold potential in treating advanced and therapy-resistant BCa.

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“…The neuroblastoma cell line was established from a bone metastasis of a stage IV neuroblastoma patient 39 , in accordance with relevant guidelines and regulations. All drug-resistant sublines had been established by continuous exposure to stepwise increasing drug concentrations as previously described 12 , 39 and were derived from the Resistant Cancer Cell Line (RCCL) collection 7 . The cisplatin-resistant ovarian cancer sublines had been adapted to 1 µg/mL (COLO-704 r CDDP 1000 ) or 2 µg/ml (EFO-27 r CDDP 2000 and EFO-21 r CDDP 2000 ) cisplatin.…”

Section: Methodsmentioning

confidence: 99%

“…Such methods may also enable the discrimination between cell lines of the same genetic origin, a task for which established methods are currently lacking. Such approaches have the potential to improve the reliability of research results due to the reduction of the use of misidentified cell lines [4][5][6][7] . By using deep learning, we have demonstrated that, it is possible to authenticate cancer cell lines, including parental cancer cell lines and their drug-adapted sublines, based on image recognition.…”

Section: Model Confidencementioning

confidence: 99%

“…Additionally, methods are needed that reliably discriminate between isogenic cell lines, such as clonal sublines and drug-adapted cancer cell lines, since this is not achievable using STR analysis. Drug-adapted cancer cell lines are used as models of acquired drug resistance and have been used to identify many relevant drug resistance mechanisms [7][8][9][10][11] . We have established the Resistant Cancer Cell Line (RCCL) collection, the worldwide largest collection of drug-adapted cancer cell lines, currently consisting of > 1,500 models of acquired resistance 12 .…”

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confidence: 99%

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Towards image-based cancer cell lines authentication using deep neural networks

Mzurikwao

Khan

Samuel

et al. 2020

Sci Rep

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Although short tandem repeat (STR) analysis is available as a reliable method for the determination of the genetic origin of cell lines, the occurrence of misauthenticated cell lines remains an important issue. Reasons include the cost, effort and time associated with STR analysis. Moreover, there are currently no methods for the discrimination between isogenic cell lines (cell lines of the same genetic origin, e.g. different cell lines derived from the same organism, clonal sublines, sublines adapted to grow under certain conditions). Hence, additional complementary, ideally low-cost and low-effort methods are required that enable (1) the monitoring of cell line identity as part of the daily laboratory routine and 2) the authentication of isogenic cell lines. In this research, we automate the process of cell line identification by image-based analysis using deep convolutional neural networks. Two different convolutional neural networks models (MobileNet and InceptionResNet V2) were trained to automatically identify four parental cancer cell line (COLO 704, EFO-21, EFO-27 and UKF-NB-3) and their sublines adapted to the anti-cancer drugs cisplatin (COLO-704rCDDP1000, EFO-21rCDDP2000, EFO-27rCDDP2000) or oxaliplatin (UKF-NB-3rOXALI2000), hence resulting in an eight-class problem. Our best performing model, InceptionResNet V2, achieved an average of 0.91 F1-score on tenfold cross validation with an average area under the curve (AUC) of 0.95, for the 8-class problem. Our best model also achieved an average F1-score of 0.94 and 0.96 on the authentication through a classification process of the four parental cell lines and the respective drug-adapted cells, respectively, on a four-class problem separately. These findings provide the basis for further development of the application of deep learning for the automation of cell line authentication into a readily available easy-to-use methodology that enables routine monitoring of the identity of cell lines including isogenic cell lines. It should be noted that, this is just a proof of principal that, images can also be used as a method for authentication of cancer cell lines and not a replacement for the STR method.

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Drug-adapted cancer cell lines as preclinical models of acquired resistance

Cited by 22 publications

References 124 publications

Shikonin Reduces Growth of Docetaxel-Resistant Prostate Cancer Cells Mainly through Necroptosis

Shikonin Reduces Growth of Docetaxel-Resistant Prostate Cancer Cells Mainly through Necroptosis

Artesunate Impairs Growth in Cisplatin-Resistant Bladder Cancer Cells by Cell Cycle Arrest, Apoptosis and Autophagy Induction

Towards image-based cancer cell lines authentication using deep neural networks

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