The BH3-only protein, PUMA, is involved in oxaliplatin-induced apoptosis in colon cancer cells

Xinying Wang; Ming Li; Jide Wang; Chung Man Yeung; Hongquan Zhang; Hsiang fu Kung; Bo Jiang; Marie Chia-mi Lin

doi:10.1016/j.bcp.2006.02.011

The BH3-only protein, PUMA, is involved in oxaliplatin-induced apoptosis in colon cancer cells

Xinying Wang, Ming Li, Jide Wang, Chung Man Yeung, Hongquan Zhang, Hsiang fu Kung, Bo Jiang, Marie Chia-mi Lin

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

Abstract

Oxaliplatin, the first line chemotherapeutic of colon cancer, induces damage to tumors via induction of apoptosis. PUMA (p53 up-regulate modulator of apoptosis) is an important pro-apoptotic member of Bcl-2 family and regulated mainly by p53. Here we investigated the role of PUMA in oxalipaltin-induced apoptosis and the potential mechanism. We showed that oxaliplatin-induced PUMA expression in a time- and dose-dependent manner and suppression of PUMA expression by stable transfecting anti-sense PUMA plasmid decreased oxaliplatin-induced apoptosis in colon cancer cells. By abrogating the function of p53, we further demonstrated that the induction was p53-independent. We also found that oxaliplatin could inactivate ERK and suppression of ERK activity by its specific inhibitor (PD98059), and dominant negative plasmid (DN-MEK1) enhanced the oxaliplatin-induced PUMA expression and apoptosis in a p53-independent manner. Taken together, our data suggest that PUMA plays an important role in oxaliplatin-induced apoptosis and the induction could be both p53-dependent and p53-independent. Moreover, PUMA expression and apoptosis in oxaliplatin-treated colon cancer cells could be regulated partly by ERK inactivation. Identification of the molecular components involved in regulating the cellular sensitivity to oxaliplatin may provide potential targets for development of novel compounds that may be useful in enhancement of oxaliplatin cytotoxicity in p53 deficient colon cancer.

Original language	English (US)
Pages (from-to)	1540-1550
Number of pages	11
Journal	Biochemical Pharmacology
Volume	71
Issue number	11
DOIs	https://doi.org/10.1016/j.bcp.2006.02.011
State	Published - May 28 2006
Externally published	Yes

Bibliographical note

Funding Information:
The authors thank Dr. Thijn R. Brummelkamp for providing the pSUPER-p53 plasmid. This work was supported by the Science and Technology Program of Guangdong province, China (2002C30307). This work was also supported in part by an AoE scheme of UGC and grants from the Research Grants Council of the Hong Kong Special Administrative Region, China (HKU 7243/02M to MCL) and grants from Li Ka Shing Institute of Health Sciences, Hong Kong, China (to HFK).

Keywords

Apoptosis
Colon cancer
ERK
Oxaliplatin
PUMA
p53

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bcp.2006.02.011

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title = "The BH3-only protein, PUMA, is involved in oxaliplatin-induced apoptosis in colon cancer cells",

abstract = "Oxaliplatin, the first line chemotherapeutic of colon cancer, induces damage to tumors via induction of apoptosis. PUMA (p53 up-regulate modulator of apoptosis) is an important pro-apoptotic member of Bcl-2 family and regulated mainly by p53. Here we investigated the role of PUMA in oxalipaltin-induced apoptosis and the potential mechanism. We showed that oxaliplatin-induced PUMA expression in a time- and dose-dependent manner and suppression of PUMA expression by stable transfecting anti-sense PUMA plasmid decreased oxaliplatin-induced apoptosis in colon cancer cells. By abrogating the function of p53, we further demonstrated that the induction was p53-independent. We also found that oxaliplatin could inactivate ERK and suppression of ERK activity by its specific inhibitor (PD98059), and dominant negative plasmid (DN-MEK1) enhanced the oxaliplatin-induced PUMA expression and apoptosis in a p53-independent manner. Taken together, our data suggest that PUMA plays an important role in oxaliplatin-induced apoptosis and the induction could be both p53-dependent and p53-independent. Moreover, PUMA expression and apoptosis in oxaliplatin-treated colon cancer cells could be regulated partly by ERK inactivation. Identification of the molecular components involved in regulating the cellular sensitivity to oxaliplatin may provide potential targets for development of novel compounds that may be useful in enhancement of oxaliplatin cytotoxicity in p53 deficient colon cancer.",

keywords = "Apoptosis, Colon cancer, ERK, Oxaliplatin, PUMA, p53",

author = "Xinying Wang and Ming Li and Jide Wang and Yeung, {Chung Man} and Hongquan Zhang and Kung, {Hsiang fu} and Bo Jiang and {Chia-mi Lin}, Marie",

note = "Funding Information: The authors thank Dr. Thijn R. Brummelkamp for providing the pSUPER-p53 plasmid. This work was supported by the Science and Technology Program of Guangdong province, China (2002C30307). This work was also supported in part by an AoE scheme of UGC and grants from the Research Grants Council of the Hong Kong Special Administrative Region, China (HKU 7243/02M to MCL) and grants from Li Ka Shing Institute of Health Sciences, Hong Kong, China (to HFK).",

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T1 - The BH3-only protein, PUMA, is involved in oxaliplatin-induced apoptosis in colon cancer cells

AU - Wang, Xinying

AU - Li, Ming

AU - Wang, Jide

AU - Yeung, Chung Man

AU - Zhang, Hongquan

AU - Kung, Hsiang fu

AU - Jiang, Bo

AU - Chia-mi Lin, Marie

N1 - Funding Information: The authors thank Dr. Thijn R. Brummelkamp for providing the pSUPER-p53 plasmid. This work was supported by the Science and Technology Program of Guangdong province, China (2002C30307). This work was also supported in part by an AoE scheme of UGC and grants from the Research Grants Council of the Hong Kong Special Administrative Region, China (HKU 7243/02M to MCL) and grants from Li Ka Shing Institute of Health Sciences, Hong Kong, China (to HFK).

PY - 2006/5/28

Y1 - 2006/5/28

N2 - Oxaliplatin, the first line chemotherapeutic of colon cancer, induces damage to tumors via induction of apoptosis. PUMA (p53 up-regulate modulator of apoptosis) is an important pro-apoptotic member of Bcl-2 family and regulated mainly by p53. Here we investigated the role of PUMA in oxalipaltin-induced apoptosis and the potential mechanism. We showed that oxaliplatin-induced PUMA expression in a time- and dose-dependent manner and suppression of PUMA expression by stable transfecting anti-sense PUMA plasmid decreased oxaliplatin-induced apoptosis in colon cancer cells. By abrogating the function of p53, we further demonstrated that the induction was p53-independent. We also found that oxaliplatin could inactivate ERK and suppression of ERK activity by its specific inhibitor (PD98059), and dominant negative plasmid (DN-MEK1) enhanced the oxaliplatin-induced PUMA expression and apoptosis in a p53-independent manner. Taken together, our data suggest that PUMA plays an important role in oxaliplatin-induced apoptosis and the induction could be both p53-dependent and p53-independent. Moreover, PUMA expression and apoptosis in oxaliplatin-treated colon cancer cells could be regulated partly by ERK inactivation. Identification of the molecular components involved in regulating the cellular sensitivity to oxaliplatin may provide potential targets for development of novel compounds that may be useful in enhancement of oxaliplatin cytotoxicity in p53 deficient colon cancer.

AB - Oxaliplatin, the first line chemotherapeutic of colon cancer, induces damage to tumors via induction of apoptosis. PUMA (p53 up-regulate modulator of apoptosis) is an important pro-apoptotic member of Bcl-2 family and regulated mainly by p53. Here we investigated the role of PUMA in oxalipaltin-induced apoptosis and the potential mechanism. We showed that oxaliplatin-induced PUMA expression in a time- and dose-dependent manner and suppression of PUMA expression by stable transfecting anti-sense PUMA plasmid decreased oxaliplatin-induced apoptosis in colon cancer cells. By abrogating the function of p53, we further demonstrated that the induction was p53-independent. We also found that oxaliplatin could inactivate ERK and suppression of ERK activity by its specific inhibitor (PD98059), and dominant negative plasmid (DN-MEK1) enhanced the oxaliplatin-induced PUMA expression and apoptosis in a p53-independent manner. Taken together, our data suggest that PUMA plays an important role in oxaliplatin-induced apoptosis and the induction could be both p53-dependent and p53-independent. Moreover, PUMA expression and apoptosis in oxaliplatin-treated colon cancer cells could be regulated partly by ERK inactivation. Identification of the molecular components involved in regulating the cellular sensitivity to oxaliplatin may provide potential targets for development of novel compounds that may be useful in enhancement of oxaliplatin cytotoxicity in p53 deficient colon cancer.

KW - Apoptosis

KW - Colon cancer

KW - ERK

KW - Oxaliplatin

KW - PUMA

KW - p53

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ER -

The BH3-only protein, PUMA, is involved in oxaliplatin-induced apoptosis in colon cancer cells

Abstract

Bibliographical note

Keywords

UN SDGs

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