Unknown,Transcriptomics,Genomics,Proteomics

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MC70 potentiates doxorubicin efficacy in colon and breast cancer in vitro treatment

ABSTRACT: A major limitation in the cancer treatment is the ability of cancer cells to become resistant to chemotherapeutic drugs, by multidrug establishment. Here, we evaluate the possibility to utilize MC70, either as ABC transporters inhibitor or as anticancer agent, in monotherapy or in combination with doxorubicin for cancer treatment. The study was carried out in MCF7/ADR and Caco-2, breast and colon cancer cells, respectively. Cell growth and apoptosis were measured by MTT assay and DNA laddering Elisa kit, respectively. Cell cycle perturbation and cellular targets modulation were analyzed by flow cytometry and western blotting, respectively. MC70 was analyzed for its interaction with ABC transporters, MDR-1, BCRP and MRP-1, and for its anticancer activity. In MCF7/ADR, MC70 slight inhibited cell proliferation and strongly enhanced doxorubicin effectiveness; conversely in Caco-2, it inhibited cell growth without affecting doxorubicin efficacy. In addition, it induced apoptosis, canceled in favor of necrosis when it was given in combination with high doses of the anthracycline. Moreover, MC70 inhibited cell migration probably through its residual activity as sigma-1 ligand. Among the hypothesized molecular and cellular mechanisms responsible for all these effects, modulations of cell cycle, of pAkt and of the three MAPKs phosphorylation were evidenced while activity at transcription level was excluded. MC70 can be considered as a potential new anticancer agent with the capability to enhance doxorubicin effectiveness and an interesting role in the treatment of chemotherapy resistant tumors. The study included the basic characterization of MC70 efficacy as inhibitor of MDR transporters, the investigation of its anticancer behavior and the exploration of the molecular and cellular mechanisms responsible for it

ORGANISM(S): Homo sapiens

SUBMITTER: Pina Iannelli

PROVIDER: E-GEOD-26250 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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MC70 potentiates doxorubicin efficacy in colon and breast cancer in vitro treatment.

Azzariti Amalia A Quatrale Anna E AE Porcelli Letizia L Colabufo Nicola A NA Cantore Mariangela M Cassano Giuseppe G Gasparre Giuseppe G Iannelli Giuseppina G Tommasi Stefania S Panaro Maria A MA Paradiso Angelo A

European journal of pharmacology 20110905 1

A major limitation of cancer treatment is the ability of cancer cells to develop resistance to chemotherapeutic drugs, by the establishment of multidrug resistance. Here, we characterize MC70 as ABC transporters inhibitor and anticancer agent, alone or with chemotherapy. MC70 was analyzed for its interaction with ABCB1, ABCG2 and ABCC1 by specific transport assays. In breast and colon cancer cell lines, cell growth and apoptosis were measured by MTT assay and DNA laddering Elisa kit, respectivel ...[more]

PMID: 21925160

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Dataset Information

MC70 potentiates doxorubicin efficacy in colon and breast cancer in vitro treatment

Publications

MC70 potentiates doxorubicin efficacy in colon and breast cancer in vitro treatment.

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