Inhibitory Effects of 12-O-Tetradecanoylphorbol-13-acetate Alone or in Combination with All-trans Retinoic Acid on the Growth of Cultured Human Pancreas Cancer Cells and Pancreas Tumor Xenografts in Immunodeficient Mice

Avila, Gina E.; Zheng, Xi; Cui, Xiao; Ryan, A; Hansson, Annette; Suh, Junghan; Rabson, Arnold B.; Chang, Richard L.; Shih, Weichung Joe; Lin, Yong; Crowell, Pamela L.; Lü, Yao; Lou, You-Rong; Conney, Allan H.

doi:10.1124/jpet.105.087585

Cited by 14 publications

(24 citation statements)

References 36 publications

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“…Low doses of TPA inhibit the growth of subcutaneous xenografts of human pancreatic cancer cells in athymic mice when administered by intraperitoneal injection. 25 Similar effects of TPA were seen on the growth of LNCaP prostate tumor in immunodifficient mice. 32 The use of TPA has been investigated in humans with acute myeloid leukemia or chronic myeloid leukemia.…”

Section: Discussionsupporting

confidence: 70%

“…The lack of apoptosis induction is similar to other reports and our own previous studies where no apoptosis was seen 5,24 ; however, this contrasts with a report in which the number of caspase 3 positive cells was increased by TPA treatment of Panc-1 pancreatic cancer xenografts in athymic mice. 25 It is possible that apoptosis is a late effect of TPA because a small sub-G0/ G1 cell population was seen after 96 hours in TPA-treated Panc-1 cells. 5 The growth inhibition of pancreatic cancer cells induced by TPA seems to be mediated through PKC because it was blocked by the specific PKC inhibitor, Bisindoylmaleimide I.…”

Section: Discussionmentioning

confidence: 98%

“…31 Although it is established that TPA inhibits pancreatic cancer cell proliferation, the phase at which TPA induces cell cycle arrest in pancreatic cancer is controversial. One study showed that TPA arrested pancreatic cancer cells in the G2/M phase, 25 whereas another study indicated that TPA arrested pancreatic cancer cells in the G1 phase. 5 The reason for this discrepancy is not clear, but it is possible that the phase of cell cycle arrest by TPA is time-dependent or that culture conditions are different.…”

Section: Discussionmentioning

confidence: 98%

“…One study showed accumulation of cells in G1 phase of the cell cycle after TPA treatment in Panc-1 cells, 5 whereas another group observed G2/M arrest in the same cell line. 25 Expression of p21 WAF1 was up-regulated in both studies. 5,25 However, the signal pathways involved in the growth inhibition are not clear.…”

mentioning

confidence: 91%

“…25 Expression of p21 WAF1 was up-regulated in both studies. 5,25 However, the signal pathways involved in the growth inhibition are not clear. In the current study, we investigated the roles of the cell cycle related proteins, p21 WAF1 , cyclin A, and cyclin B in the growth-inhibitory effects of TPA.…”

mentioning

confidence: 91%

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On the Mechanisms of 12-Otetradecanoylphorbol-13-acetate-induced Growth Arrest in Pancreatic Cancer Cells

Salabat

Ding²,

Flesche³

et al. 2006

Pancreas

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 91%

mentioning

confidence: 91%

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On the Mechanisms of 12-Otetradecanoylphorbol-13-acetate-induced Growth Arrest in Pancreatic Cancer Cells

Salabat

Ding²,

Flesche³

et al. 2006

Pancreas

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Incidence of noncutaneous melanomas in the U.S.

McLaughlin

Jemal

et al. 2005

Cancer

650

462

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BACKGROUNDDescription of the epidemiology of noncutaneous melanoma has been hampered by its rarity. The current report was the largest in‐depth descriptive analysis of incidence of noncutaneous melanoma in the United States, using data from the North American Association of Central Cancer Registries.METHODSPooled data from 27 states and one metropolitan area were used to examine the incidence of noncutaneous melanoma by anatomic subsite, gender, age, race, and geography (northern/southern and coastal/noncoastal) for cases diagnosed between 1996 and 2000. Percent distribution by stage of disease at diagnosis and histology were also examined.RESULTSBetween 1996 and 2000, 6691 cases of noncutaneous melanoma (4885 ocular and 1806 mucosal) were diagnosed among 851 million person‐years at risk. Ocular melanoma was more common among men compared with women (6.8 cases per million men compared with 5.3 cases per million women, age‐adjusted to the 2000 U.S. population standard), whereas mucosal melanoma was more common among women (2.8 cases per million women compared with 1.5 cases per million men). Rates of ocular melanoma among whites were greater than eight times higher than among blacks. Rates of mucosal melanoma were approximately two times higher among whites compared with blacks.CONCLUSIONSIn contrast to cutaneous melanoma, there was no apparent pattern of increased noncutaneous melanoma among residents of southern or coastal states, with the exception of melanoma of the ciliary body and iris. Despite their shared cellular origins, both ocular and mucosal melanomas differ from cutaneous melanoma in terms of incidence by gender, race, and geographic area. Cancer 2005. © 2005 American Cancer Society.

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Cytotoxic action of phorbol esters on human pancreatic cancer cells

Bond

Gescher

Verschoyle

et al. 2007

Intl Journal of Cancer

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We previously showed that phorbol esters are cytotoxic to human thyroid epithelial cells expressing a mutant RAS oncogene. Here we explore the generality of this finding using cells derived from pancreatic cancer, which, like thyroid, shows a high frequency of RAS mutation, but is a much greater cause of cancer mortality. The response to phorbol myristate acetate (PMA) and related agents was assessed on a panel of 9 pancreatic cancer cell lines, using a range of assays for cell growth and death in vitro and in vivo. In most lines, PMA induced non-apoptotic cell death which was, surprisingly, independent of its ''classic'' target, protein kinase C. With 24 hr exposure, the IC 50 in the most sensitive line (Aspc-1) was <1 ng/ml (1.6 nM), with survival undetectable at concentrations 16 nM, and after only 1 hr exposure the IC 50 was still 16 nM. Interestingly, the efficacy of a second phorbol ester, phorbol dibutyrate, was much lower, and the PMA analogue bryostatin-1, which is in clinical trials against other tumour types, was totally inactive. Pre-treatment of Aspc-1 cells with PMA before subcutaneous inoculation into nude mice prevented, or greatly retarded, subsequent xenograft tumour growth. Furthermore, treatment of established tumours with a single peri-tumoral injection of PMA induced extensive cell death and arrested tumour development. Taken together with recent Phase 1 clinical studies, these data suggest that activity against pancreatic cancer will be attainable by systemic administration of PMA, and point to potential novel therapeutic targets for this highly aggressive cancer. ' 2007 Wiley-Liss, Inc.

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Inhibitory Effects of 12-O-Tetradecanoylphorbol-13-acetate Alone or in Combination with All-trans Retinoic Acid on the Growth of Cultured Human Pancreas Cancer Cells and Pancreas Tumor Xenografts in Immunodeficient Mice

Cited by 14 publications

References 36 publications

On the Mechanisms of 12-Otetradecanoylphorbol-13-acetate-induced Growth Arrest in Pancreatic Cancer Cells

On the Mechanisms of 12-Otetradecanoylphorbol-13-acetate-induced Growth Arrest in Pancreatic Cancer Cells

Incidence of noncutaneous melanomas in the U.S.

Cytotoxic action of phorbol esters on human pancreatic cancer cells

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