Suppression of breast cancer growth and angiogenesis by an antisense oligodeoxynucleotide to p21Waf1/Cip1

Weiss, Robert H.; Marshall, Debbie; Howard, Laura L.; Corbacho, Ana; Cheung, Anthony; Sawai, Earl T.

doi:10.1016/s0304-3835(02)00495-0

Cited by 44 publications

(32 citation statements)

References 31 publications

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“…Compared with the use of peptides, small molecule inhibitors or antisense techniques (Lam et al, 2003;Weiss et al, 2003), we consider that triptoide may be a more convenient, realistic and attractive p21 attenuation method, because triptolide is a common drug and exhibits cancer-specific p21 attenuation. Furthermore, this synergic effect of triptolide was not limited within urothelium or CDDP treatment.…”

Section: Discussionmentioning

confidence: 99%

Cancer-specific enhancement of cisplatin-induced cytotoxicity with triptolide through an interaction of inactivated glycogen synthase kinase-3β with p53

et al. 2008

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To improve conventional chemotherapeutic efficacy, a combination use of traditional medicines is effective but detailed mechanisms have been rarely elucidated. In the this study, we attempted to clarify how triptolide (PG490), an oxygenated diterpene derived from a Chinese herb, enhances the cisplatin (CDDP)-induced cytotoxicity in urothelial cancer cells. Our results showed that a combined CDDP/triptolide therapy induced apoptosis in urothelial cancer cell lines with wild-type p53, but not in those with mutant-type p53 or normal human urothelium. As the mechanism, triptolide suppressed CDDP-induced p53 transcriptional activity, leading to p21 attenuation, which promoted apoptosis via the activation of c-Jun N-terminal kinase (JNK) and Bax. We further demonstrated that the functional regulation of p53 by triptolide was mediated by an intranuclear association of p53 with glycogen synthase kinase-3b (GSK3b), which was inactivated by protein kinase C (PKC). This modulation of the PKC-GSK3b axis by triptolide was observed in a cancer-specific manner. A mouse xenograft model also showed that a combined CDDP/triptolide therapy completely suppressed tumor growth without any side effects. We expect that cancer-specific enhancement of CDDP-induced cytotoxicity with triptolide may effectively overcome the resistance to a CDDP-based conventional chemotherapy as a treatment for urothelial cancer.

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Section: Discussionmentioning

confidence: 99%

Cancer-specific enhancement of cisplatin-induced cytotoxicity with triptolide through an interaction of inactivated glycogen synthase kinase-3β with p53

et al. 2008

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“…[140][141][142] Interestingly, and paradoxically, when expressed at very low levels, p21 CIP1/WAF1 is required for the assembly of cyclin D/cdk complexes and is therefore an important component of cell cycle progression. 143,144 Furthermore, p21 CIP1/WAF1 has been shown to directly inhibit caspase-3 activation, thereby preventing apoptosis. 143,144 Indeed, down-regulation of p21 CIP1/WAF1 in tumor cells was found to lead to increased apoptosis.…”

Section: The Molecular Targets Of Iron Chelators and Their Effects Onmentioning

confidence: 99%

“…143,144 Furthermore, p21 CIP1/WAF1 has been shown to directly inhibit caspase-3 activation, thereby preventing apoptosis. 143,144 Indeed, down-regulation of p21 CIP1/WAF1 in tumor cells was found to lead to increased apoptosis. 145 Although often activated by p53 in response to cellular stress and/ or DNA damage, p21 CIP1/WAF1 can also be induced by p53-independent pathways involving other transcription factors such as AP2, Sp1 or Sp3.…”

Section: The Molecular Targets Of Iron Chelators and Their Effects Onmentioning

confidence: 99%

Tuning Cell Cycle Regulation with an Iron Key

Yu¹,

Kovačević²,

Richardson³

2007

Cell Cycle

218

190

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“…Cip1/WAF1 in vivo and in vitro has been shown to be a sensitive way to examine its role in the inhibition of cell proliferation, angiogenesis, matrix protein production, and induction of apoptosis (Tian et al 2000, Weiss et al 2003. Noteworthy, the inhibitory effect exerted by BRL on cell proliferation was reversed by p21…”

Section: Bonofiglio H Qi Et Al: Pparg Regulates P21mentioning

confidence: 99%

Peroxisome proliferator-activated receptor inhibits follicular and anaplastic thyroid carcinoma cells growth by upregulating p21Cip1/WAF1 gene in a Sp1-dependent manner

Bonofiglio¹,

Qi²,

Gabriele³

et al. 2008

Endocrine Related Cancer

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Peroxisome proliferator-activated receptor g (PPARg) has been demonstrated to be antineoplastic against various human tumors. The aim of this study was to delineate the molecular mechanism underlying PPARg ligand rosiglitazone (BRL) antiproliferative effects in follicular WRO and anaplastic FRO human thyroid carcinoma cells. BRL upregulated the p21Cip1/WAF1 levels in the two thyroid cancer cells, while did not modify the p53 protein content. Different evidences indicate that the p21 Cip1/WAF1 upregulation by BRL requires a functional PPARg, since it was reversed by silencing PPARg and pretreatment with GW9662, an irreversible PPARg antagonist. Transient transfection assays showed that BRL triggered the transcriptional activity of p21Cip1/WAF1 promoter gene in a p53-independent way, being a p21 Cip1/WAF1 promoter construct deleted in the p53 sites still activated by BRL. The Sp1 inhibitor mithramycin silenced the p21 Cip1/WAF1 promoter activity suggesting an important role of Sp1 in mediating BRL activation. The electrophoretic mobility shift and chromatin immunoprecipitation (ChIP) assays evidenced a functional interaction between PPARg and Sp1 in regulating p21Cip1/WAF1 . Intriguingly, ChIP analysis revealed in the p21 Cip1/WAF1 gene promoter an increased recruitment of the RNA Pol II associated with an increased histone H3 acetylation and a reduced H3 methylation. The biological event, consistent with PPARg-induced WRO and FRO cell growth inhibition, was reversed by p21Cip1/WAF1 antisense oligonucleotides and was confirmed by increasing the PPARg expression, suggesting a crucial role exerted by p21Cip1/WAF1 in PPARg action. Our results further candidate BRL as a potential agent able to inhibit tumor progression of follicular and anaplastic thyroid carcinoma.

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Suppression of breast cancer growth and angiogenesis by an antisense oligodeoxynucleotide to p21Waf1/Cip1

Cited by 44 publications

References 31 publications

Cancer-specific enhancement of cisplatin-induced cytotoxicity with triptolide through an interaction of inactivated glycogen synthase kinase-3β with p53

Cancer-specific enhancement of cisplatin-induced cytotoxicity with triptolide through an interaction of inactivated glycogen synthase kinase-3β with p53

Tuning Cell Cycle Regulation with an Iron Key

Peroxisome proliferator-activated receptor inhibits follicular and anaplastic thyroid carcinoma cells growth by upregulating p21Cip1/WAF1 gene in a Sp1-dependent manner

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