English Journal

CHAG priming regimen containing of cytarabine, aclacinomycin homoharringtonine and G-CSF for relapsed refractory acute myelogenous leukemia: a modified combination chemotherapeutic combination.

Chen L, Yin Q, Mi R, Wei X.
Leukemia & lymphoma.Leuk Lymphoma.2013 Oct;54(10):2291-3. doi: 10.3109/10428194.2013.772295. Epub 2013 Mar 8.
PMID 23369043

High-throughput screening identifies aclacinomycin as a radiosensitizer of EGFR-mutant non-small cell lung cancer.

Bennett DC, Charest J, Sebolt K, Lehrman M, Rehemtulla A, Contessa JN.Author information Department of Therapeutic Radiology, Yale University, New Haven, CT.AbstractThe endoplasmic reticulum (ER) provides a specialized environment for the folding and modification of trans-membrane proteins, including receptor tyrosine kinases (RTKs), which are vital for the growth and survival of malignancies. To identify compounds which disrupt the function of the ER and thus could potentially impair cancer cell survival signaling, we adapted a set of glycosylation-sensitive luciferase reporters for the development and optimization of a cell-based high-throughput screen (HTS). Secondary screens for false-positive luciferase activation and tertiary lectin-based and biochemical analyses were also devised for compound triage. Through a pilot screen of 2802 compounds from the National Cancer Institute (NCI) chemical libraries, we identified aclacinomycin (Acm) as a compound that preferentially affects ER function. We report that Acm reduces plasma membrane expression of glycoproteins including epidermal growth factor receptor (EGFR) and Met but does not inhibit N-linked glycosylation or generalized protein translation. Fluorescence microscopy co-localization experiments were also performed and demonstrated Acm accumulation in the ER in further support of the overall HTS design. The consequences of Acm treatment on cell survival were analyzed through clonogenic survival analysis. Consistent with the reduction of EGFR levels, pretreatment with Acm sensitizes the EGFR-mutant non-small cell lung cancer (NSCLC) cell lines HCC827 and HCC2935 to ionizing radiation and did not affect the sensitivity of the RTK-independent and KRAS-mutant A549 NSCLC cell line. Thus, Acm and similar compounds targeting the ER may represent a novel approach for radiosensitizing tumor cells dependent on RTK function.
Translational oncology.Transl Oncol.2013 Jun 1;6(3):382-91. Print 2013 Jun.
The endoplasmic reticulum (ER) provides a specialized environment for the folding and modification of trans-membrane proteins, including receptor tyrosine kinases (RTKs), which are vital for the growth and survival of malignancies. To identify compounds which disrupt the function of the ER and thus
PMID 23730419

Japanese Journal

Novel derivatives of aclacinomycin A block cancer cell migration through inhibition of farnesyl transferase

Journal of antibiotics 66(3), 165-170, 2013-03-25
NAID 10031163117

Characterization of rhodosaminyl transfer by the AknS/AknT glycosylation complex and its use in reconstituting the biosynthetic pathway of aclacinomycin A

J. Am. Chem. Soc. 129, 10546-10550, 2007
NAID 80018219998

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