Mitomycin C treatment induces resistance and enhanced migration via phosphorylated Akt in aggressive lung cancer cells

Shen, Cheng; Chen, Li Han; Lin, Yu Fen; Lai, Liang‐Chuan; Chuang, Eric Y.; Tsai, Meng-Tsan

doi:10.18632/oncotarget.13237

Cited by 5 publications

(4 citation statements)

References 51 publications

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“…Thus far, 11 clinical trials evaluate Mitomycin to treat lung cancers ( ). In fact, this drug is already indicated for certain lung cancer types (Drugbank ID: DB00305), e.g., it has been used since 1984 for non-small cell lung cancers [ 36 ]. Mitomycin is an antibiotic produced by amongst others the actinobacteria Streptomyces caespitosus .…”

Section: Resultsmentioning

confidence: 99%

Concise Polygenic Models for Cancer-Specific Identification of Drug-Sensitive Tumors from Their Multi-Omics Profiles

2020

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In silico models to predict which tumors will respond to a given drug are necessary for Precision Oncology. However, predictive models are only available for a handful of cases (each case being a given drug acting on tumors of a specific cancer type). A way to generate predictive models for the remaining cases is with suitable machine learning algorithms that are yet to be applied to existing in vitro pharmacogenomics datasets. Here, we apply XGBoost integrated with a stringent feature selection approach, which is an algorithm that is advantageous for these high-dimensional problems. Thus, we identified and validated 118 predictive models for 62 drugs across five cancer types by exploiting four molecular profiles (sequence mutations, copy-number alterations, gene expression, and DNA methylation). Predictive models were found in each cancer type and with every molecular profile. On average, no omics profile or cancer type obtained models with higher predictive accuracy than the rest. However, within a given cancer type, some molecular profiles were overrepresented among predictive models. For instance, CNA profiles were predictive in breast invasive carcinoma (BRCA) cell lines, but not in small cell lung cancer (SCLC) cell lines where gene expression (GEX) and DNA methylation profiles were the most predictive. Lastly, we identified the best XGBoost model per cancer type and analyzed their selected features. For each model, some of the genes in the selected list had already been found to be individually linked to the response to that drug, providing additional evidence of the usefulness of these models and the merits of the feature selection scheme.

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Section: Resultsmentioning

confidence: 99%

Concise Polygenic Models for Cancer-Specific Identification of Drug-Sensitive Tumors from Their Multi-Omics Profiles

2020

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“…Many cytotoxic drugs, including MMC, activate apoptosis but also autophagy, as a mechanism of resistance [13,35]. For cancer cells, the activation of autophagy may be a stimulus for survival from drug-induced bioenergetic stress.…”

Section: Discussionmentioning

confidence: 99%

Electrochemotherapy with Mitomycin C Potentiates Apoptosis Death by Inhibiting Autophagy in Squamous Carcinoma Cells

Condello

D'Avack

Vona³

et al. 2021

Cancers

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We investigated the chemosensitizing effect of electroporation (EP), which, using electrical pulses, permeabilizes cancer cells to drugs. The study involved two human hypopharyngeal and tongue carcinoma cell lines. The surface and intracytoplasmic expression of P-gp were evaluated by flow cytometry, demonstrating that both lines were intrinsically resistant. After establishing the optimal dose of mitomycin C (MMC) to be used, in combination with EP, we showed, by both MTT assay and optical and electron scanning microscopy, the potentiating cytotoxic effect of EP with MMC compared to single treatments. Flow cytometry showed that the cytotoxicity of EP + MMC was due to the induction of apoptosis. In addition to verifying the release of cytochrome C in EP + MMC samples, we performed an expression analysis of caspase-3, caspase-9, Akt, pAkt, HMGB1, LC3I, LC3II, p62, Beclin1, and associated proteins with both apoptotic and autophagic phenomena. Our results were confirmed by two veterinary patients in whom the EP + MMC combination was used to control margins after the resection of corneal squamous carcinoma. In conclusion, we affirmed that the effect for which EP enhances MMC treatment is due to the inhibition of the autophagic process induced by the drug in favor of apoptosis.

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“…Mitomycin C is commonly used as a cytotoxic agent against hematological malignancies and other cancers 101 . It has been used to treat NSCLC since 1984, 102 and it can be combined with platinum‐based drugs, docetaxel, and other chemotherapies, to improve its response rate 103 …”

Section: Antineoplastic Drugs Classified By Sourcementioning

confidence: 99%

Perspectives and controversies regarding the use of natural products for the treatment of lung cancer

2021

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Mitomycin C treatment induces resistance and enhanced migration via phosphorylated Akt in aggressive lung cancer cells

Cited by 5 publications

References 51 publications

Concise Polygenic Models for Cancer-Specific Identification of Drug-Sensitive Tumors from Their Multi-Omics Profiles

Concise Polygenic Models for Cancer-Specific Identification of Drug-Sensitive Tumors from Their Multi-Omics Profiles

Electrochemotherapy with Mitomycin C Potentiates Apoptosis Death by Inhibiting Autophagy in Squamous Carcinoma Cells

Perspectives and controversies regarding the use of natural products for the treatment of lung cancer

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