Abstract
Despite rapid progress in anticancer drug development and improvement in clinical outcomes, the survival rate for many types of cancer is still unacceptably low. Therefore, it is crucial to discover novel anticancer drugs to both prevent and treat the disease. In recent years, the advent of combinatorial chemistry allows the design and parallel synthesis of millions of small compounds that have drug-like properties. In vitro high throughput screening of such compound libraries has allowed the identification of many new drug candidates that may be further evaluated for their efficacy and mechanism of action. The overall objective of this study was to identify small molecule compounds as candidates for anti-cancer drug development. We first used cell proliferation and cytotoxicity assays to identify compounds exhibiting anti-cancer activity in vitro in a leukemia cell line (K562). Six top compounds selected from the initial screening of a library of 2,560 compounds were further evaluated in multiple cancer cell lines to rank the drug candidates. The top candidate was further investigated to elucidate the molecular mechanism underlying its anticancer activity. Our studies suggest that this piperazine derivative effectively (GI50 = 0.06-0.16 μM) inhibits cancer cell proliferation and induces caspase-dependent apoptosis via inhibiting multiple cancer signaling pathways including the PI3K/AKT, the Src family kinases and the BCR-ABL pathways.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 622-633 |
| Number of pages | 12 |
| Journal | American Journal of Translational Research |
| Volume | 5 |
| Issue number | 6 |
| State | Published - Jan 1 2013 |
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Keywords
- Apoptosis
- Cancer
- Drug discovery
- High throughput screening
- Leukemia
- Piperazine
ASJC Scopus subject areas
- Molecular Medicine
- Clinical Biochemistry
- Cancer Research
Cite this
A novel piperazine derivative potently induces caspase-dependent apoptosis of cancer cells via inhibition of multiple cancer signaling pathways. / She, Edward X.; Hao, Zhonglin.
In: American Journal of Translational Research, Vol. 5, No. 6, 01.01.2013, p. 622-633.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A novel piperazine derivative potently induces caspase-dependent apoptosis of cancer cells via inhibition of multiple cancer signaling pathways
AU - She, Edward X.
AU - Hao, Zhonglin
PY - 2013/1/1
Y1 - 2013/1/1
N2 - Despite rapid progress in anticancer drug development and improvement in clinical outcomes, the survival rate for many types of cancer is still unacceptably low. Therefore, it is crucial to discover novel anticancer drugs to both prevent and treat the disease. In recent years, the advent of combinatorial chemistry allows the design and parallel synthesis of millions of small compounds that have drug-like properties. In vitro high throughput screening of such compound libraries has allowed the identification of many new drug candidates that may be further evaluated for their efficacy and mechanism of action. The overall objective of this study was to identify small molecule compounds as candidates for anti-cancer drug development. We first used cell proliferation and cytotoxicity assays to identify compounds exhibiting anti-cancer activity in vitro in a leukemia cell line (K562). Six top compounds selected from the initial screening of a library of 2,560 compounds were further evaluated in multiple cancer cell lines to rank the drug candidates. The top candidate was further investigated to elucidate the molecular mechanism underlying its anticancer activity. Our studies suggest that this piperazine derivative effectively (GI50 = 0.06-0.16 μM) inhibits cancer cell proliferation and induces caspase-dependent apoptosis via inhibiting multiple cancer signaling pathways including the PI3K/AKT, the Src family kinases and the BCR-ABL pathways.
AB - Despite rapid progress in anticancer drug development and improvement in clinical outcomes, the survival rate for many types of cancer is still unacceptably low. Therefore, it is crucial to discover novel anticancer drugs to both prevent and treat the disease. In recent years, the advent of combinatorial chemistry allows the design and parallel synthesis of millions of small compounds that have drug-like properties. In vitro high throughput screening of such compound libraries has allowed the identification of many new drug candidates that may be further evaluated for their efficacy and mechanism of action. The overall objective of this study was to identify small molecule compounds as candidates for anti-cancer drug development. We first used cell proliferation and cytotoxicity assays to identify compounds exhibiting anti-cancer activity in vitro in a leukemia cell line (K562). Six top compounds selected from the initial screening of a library of 2,560 compounds were further evaluated in multiple cancer cell lines to rank the drug candidates. The top candidate was further investigated to elucidate the molecular mechanism underlying its anticancer activity. Our studies suggest that this piperazine derivative effectively (GI50 = 0.06-0.16 μM) inhibits cancer cell proliferation and induces caspase-dependent apoptosis via inhibiting multiple cancer signaling pathways including the PI3K/AKT, the Src family kinases and the BCR-ABL pathways.
KW - Apoptosis
KW - Cancer
KW - Drug discovery
KW - High throughput screening
KW - Leukemia
KW - Piperazine
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M3 - Article
AN - SCOPUS:84885028019
VL - 5
SP - 622
EP - 633
JO - American Journal of Translational Research
JF - American Journal of Translational Research
SN - 1943-8141
IS - 6
ER -