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Tumor Biology

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01.02.2016 | Original Article

Pre-clinical characterization of 4SC-202, a novel class I HDAC inhibitor, against colorectal cancer cells

verfasst von: Huang Zhijun, Wang Shusheng, Min Han, Li Jianping, Qin Li-sen, Li Dechun

Erschienen in: Tumor Biology | Ausgabe 8/2016

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Abstract

Histone deacetylase (HDAC) overactivity in colorectal cancer (CRC) promotes cancer progression. In the current study, we showed that 4SC-202, a novel class I HDAC inhibitor (HDACi), potently inhibited survival and proliferation of primary human colon cancer cells and established CRC lines (HT-29, HCT-116, HT-15, and DLD-1). Yet, the same 4SC-202 treatment was non-cytotoxic to colon epithelial cells where HDAC-1/-2 expressions were extremely low. 4SC-202 provoked apoptosis activation in CRC cells, while caspase inhibitors (z-VAD-CHO and z-DVED-CHO) significantly alleviated 4SC-202-exerted cytotoxicity in CRC cells. Meanwhile, 4SC-202 induced dramatic G2-M arrest in CRC cells. Further studies showed that AKT activation might be an important resistance factor of 4SC-202. 4SC-202-induced cytotoxicity was dramatically potentiated with serum starvation, AKT inhibition (by perifosine or MK-2206), or AKT1-shRNA knockdown in CRC cells. On the other hand, exogenous expression of constitutively active AKT1 (CA-AKT1) decreased the sensitivity by 4SC-202 in HT-29 cells. Notably, 4SC-202, at a low concentration, enhanced oxaliplatin-induced in vitro anti-CRC activity. In vivo, we showed that oral gavage of 4SC-202 inhibited HT-29 xenograft growth in nude mice, and when combined with oxaliplatin, its activity was further strengthened. Together, these pre-clinical results indicate that 4SC-202 may be further investigated as a valuable anti-CRC agent/chemo-adjuvant.

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Titel: Pre-clinical characterization of 4SC-202, a novel class I HDAC inhibitor, against colorectal cancer cells
verfasst von: Huang Zhijun
Wang Shusheng
Min Han
Li Jianping
Qin Li-sen
Li Dechun
Publikationsdatum: 01.02.2016
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 8/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-016-4868-6

Springer Medizin

Pre-clinical characterization of 4SC-202, a novel class I HDAC inhibitor, against colorectal cancer cells

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

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