ArticleEndocrine2014
Mitotane enhances doxorubicin cytotoxic activity by inhibiting P-gp in human adrenocortical carcinoma cells.
Article in Endocrine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- Mitigating subtherapeutic cabozantinib exposure after prior mitotane therapy in adrenocortical carcinoma: Pharmacological boosting with cobicistat.British journal of clinical pharmacology · 2026Article
- Oncological Management of Adrenocortical Carcinoma: An Update and Critical Review.Oncology and therapy · 2025Review
- Change of treatment modality and outcomes of adrenocortical carcinoma: a retrospective review of single tertiary center experience over 24 years.Gland surgery · 2022Article
- Cancer chemotherapy: insights into cellular and tumor microenvironmental mechanisms of action.Frontiers in oncology · 2022Review
- Alterations in the glycome after HDAC inhibition impact oncogenic potential in epigenetically plastic SW13 cells.BMC cancer · 2019Article
- Adrenal cavernous hemangioma: a case report.BMC surgery · 2018Article
- PI3K/Akt/mTOR pathway involvement in regulating growth hormone secretion in a rat pituitary adenoma cell line.Endocrine · 2018Article
- Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection.Journal of virology · 2017Article
- Growth Hormone differentially modulates chemoresistance in human endometrial adenocarcinoma cell lines.Endocrine · 2017Article
- Mechanisms of P-Glycoprotein Modulation by Semen Strychni Combined with Radix Paeoniae Alba.Evidence-based complementary and alternative medicine : eCAM · 2017Article
- Article
- The aurora kinase inhibitor VX-680 shows anti-cancer effects in primary metastatic cells and the SW13 cell line.Investigational new drugs · 2016Article
- Outcomes of Adjuvant Mitotane after Resection of Adrenocortical Carcinoma: A 13-Institution Study by the US Adrenocortical Carcinoma Group.Journal of the American College of Surgeons · 2016Article
- Article
- Igf-I influences everolimus activity in medullary thyroid carcinoma.Frontiers in endocrinology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitotane is currently employed as adjuvant therapy as well as in the medical treatment of adrenocortical carcinoma (ACC), alone or in combination with chemotherapeutic agents. It was previously demonstrated that mitotane potentiates chemotherapeutic drugs cytotoxicity in cancer cells displaying chemoresistance due to P-glycoprotein (P-gp), an efflux pump involved in cancer multidrug resistance. The majority of ACC expresses high levels of P-gp and is highly chemoresistent. The aim of our study was to explore in vitro whether mitotane, at concentrations lower than those currently reached in vivo, may sensitize ACC cells to the cytotoxic effects of doxorubicin and whether this effect is due to a direct action on P-gp. NCI-H295 and SW13 cell lines as well as 4 adrenocortical neoplasia primary cultures were treated with mitotane and doxorubicin, and cell viability was measured by MTT assay. P-gp activity was measured by calcein and P-gp-Glo assays. P-gp expression was evaluated by Western blot. We found that very low mitotane concentrations sensitize ACC cells to the cytotoxic effects of doxorubicin, depending on P-gp expression. In addition, mitotane directly inhibits P-gp detoxifying function, allowing doxorubicin cytotoxic activity. These data provide the basis for the greater efficacy of combination therapy (mitotane plus chemotherapeutic drugs) on ACC patients. Shedding light on mitotane mechanisms of action could result in an improved design of drug therapy for patients with ACC.
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