Effects of 12-<i>O</i>-Tetradecanoylphorbol-13-acetate (TPA) in Combination with Paclitaxel (Taxol) on Prostate Cancer LNCaP Cells Cultured <i>In vitro</i> or Grown as Xenograft Tumors in Immunodeficient Mice

Zheng, Xi; Chang, Richard L.; Cui, Xiao; Avila, Gina E.; Hebbar, Vidya; Garzotto, Mark; Shih, Weichung Joe; Lin, Yong; Lu, Shou En; Rabson, Arnold B.; Kong, Ah Ng Tony; Conney, Allan H.

doi:10.1158/1078-0432.ccr-05-2823

Cited by 24 publications

(25 citation statements)

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“…Hence, we chose to use paclitaxel chemotherapy in our assessment of 123 I-MIP-1072 to determine whether it can monitor the progression or regression of disease with external imaging. Several reports have shown growth inhibition of LNCaP xenografts by paclitaxel (28,29). Consistent with these reports, we demonstrated a 40%-50% inhibition of LNCaP and 22Rv1 cell growth in culture after 48 h and a 22% growth reduction of LNCaP xenografts by paclitaxel.…”

Section: Discussionsupporting

confidence: 91%

¹²³I-MIP-1072, a Small-Molecule Inhibitor of Prostate-Specific Membrane Antigen, Is Effective at Monitoring Tumor Response to Taxane Therapy

Hillier¹,

Kern

Maresca

et al. 2011

J Nucl Med

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Section: Discussionsupporting

confidence: 91%

¹²³I-MIP-1072, a Small-Molecule Inhibitor of Prostate-Specific Membrane Antigen, Is Effective at Monitoring Tumor Response to Taxane Therapy

Hillier¹,

Kern

Maresca

et al. 2011

J Nucl Med

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“…43 In a preclinical study on prostate cancer cells, phorbol esters (TPA) and paclitaxel in combination had a stronger inhibitory effect on the growth of tumor cells both in vitro and in vivo, suggesting the possibility of using TPA alone or in combination with paclitaxel in patients with prostate cancer. 44 Moreover, phorbol esters are also administered at very low concentrations in patients with myeloid leukemias. 31,34,35 On the contrary, in a phase 1 clinical trial with escalating doses of phorbol esters in patients with relapsed or refractory malignancies, serious adverse events were described at high doses of administration.…”

Section: Introductionmentioning

confidence: 99%

Phorbol ester–induced PKCϵ down-modulation sensitizes AML cells to TRAIL-induced apoptosis and cell differentiation

Gobbi¹,

Mirandola²,

Carubbi³

et al. 2009

Blood

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Despite the relevant therapeutic progresses made in these last 2 decades, the prognosis of acute myeloid leukemia (AML) remains poor. Phorbol esters are used at very low concentrations as differentiating agents in the therapy of myeloid leukemias. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), in turn, is a death ligand that spares normal cells and is therefore currently under clinical trials for cancer therapy. Emerging evidence, however, suggests that TRAIL is also involved in nonapoptotic functions, like cell differentiation. PKC⑀ is differentially modulated along normal hematopoiesis, and its levels modulate the response of hematopoietic precursors to TRAIL. Here, we investigated the effects of the combination of phorbol esters (phorbol ester 4-␤-phorbol-12,13-dibutyrate [PDBu]) and TRAIL in the survival/differentiation of AML cells. We demonstrate here that PDBu sensitizes primary AML cells to both the apoptogenic and the differentiative effects of TRAIL via PKC⑀ down-modulation, without affecting TRAIL receptor surface expression. We believe that the use of TRAIL in combination with phorbol esters (or possibly more specific PKC⑀ down-modulators) might represent a significative improvement of our therapeutic arsenal against AML. (Blood. 2009;113:3080-3087) IntroductionAlthough these last 2 decades have seen relevant progresses in the therapy of acute myelogenous leukemia (AML) in terms of cytogenetic prognostic factors, bone marrow transplantation, and targeted therapies, 1 the 5-year survival rate is still 20% to 30% 2 for adult primary AML, and is even worse for AML arising from myeloproliferative disorders or myelodysplastic syndromes (MDSs). 3 Moreover, conventional antitumor treatments make a selective pressure for p53-inactivated tumor cells, and the development of drug resistance remains a serious problem. In this context, a special effort is currently dedicated to targeted therapies whose cornerstones-at least in terms of clinical success-have been all-trans retinoic acid (ATRA) for promyelocytic leukemia 4,5 and imatinib for chronic myelogenous leukemia, 6 while several other compounds-including apoptosis inducers and antiapoptotic inhibitors-are in the pipeline in the future perspective of combinations of multiple targeted therapies for the treatment of AML.Recombinant, soluble tumor necrosis factor-related apoptosisinducing ligand (TRAIL) is currently being developed as a promising natural immune molecule for patients with cancer because it selectively induces apoptosis in transformed or stressed cells but not in most normal cells. 7 Although primary AML cells are generally resistant to TRAIL-induced apoptosis in patients with cancer, phase 1 and 2 clinical trials using agonistic mAbs that engage the human TRAIL receptors 1 (TRAIL-R1) and 2 (TRAIL-R2) have also provided encouraging results. 7 Although hepatotoxicity was observed as side effect using agonistic antibodies against TRAIL-R2, 8 the emerging idea is that TRAIL will likely be used as one component of more complex antit...

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“…Dose-response studies on the effects of atorvastatin, celecoxib or tipifarnib on the growth and apoptosis of cultured Panc-1 cells using our previously utilized methodology (13,14,18) are shown in Fig. 2.…”

Section: Resultsmentioning

confidence: 99%

A triple combination of atorvastatin, celecoxib and tipifarnib strongly inhibits pancreatic cancer cells and xenograft pancreatic tumors

Ding

Cui

Zhi

et al. 2014

International Journal of Oncology

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Because K-Ras mutation and cyclooxygenase-2 (COX-2) overexpression are hallmarks of majority of pancreatic cancer patients, an approach to inhibit the progression and growth of pancreatic cancer using the simultaneous administration of agents that inhibit the function of both targets, should be considered. In the present study, we assessed the effects of atorvastatin (Lipitor), celecoxib (Celebrex) and tipifarnib (Zarnestra) on the growth of human pancreatic cancer. In the in vitro studies, we found that treatment of human pancreatic tumor cells with a combination of atorvastatin, celecoxib and tipifarnib had a stronger inhibitory effect on growth and a stronger stimulatory effect on apoptosis than each drug alone or for any combination of two drugs. We also found that treatment of Panc-1 cells with a combination of all three drugs strongly decreased the levels of phosphorylated Erk1/2 and Akt. In an animal model of xenograft tumors in severe combined immunodeficient (SCID) mice, we found that daily i.p. injections of a combination of atorvastatin, celecoxib and tipifarnib had a stronger inhibitory effect on the growth of the tumors in mice than each drug alone or for any combination of two drugs. The results of our study indicate that a combination of atorvastatin, celecoxib and tipifarnib may be an effective strategy for the treatment of pancreatic cancer.

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Effects of 12-O-Tetradecanoylphorbol-13-acetate (TPA) in Combination with Paclitaxel (Taxol) on Prostate Cancer LNCaP Cells Cultured In vitro or Grown as Xenograft Tumors in Immunodeficient Mice

Cited by 24 publications

References 25 publications

¹²³I-MIP-1072, a Small-Molecule Inhibitor of Prostate-Specific Membrane Antigen, Is Effective at Monitoring Tumor Response to Taxane Therapy

¹²³I-MIP-1072, a Small-Molecule Inhibitor of Prostate-Specific Membrane Antigen, Is Effective at Monitoring Tumor Response to Taxane Therapy

Phorbol ester–induced PKCϵ down-modulation sensitizes AML cells to TRAIL-induced apoptosis and cell differentiation

A triple combination of atorvastatin, celecoxib and tipifarnib strongly inhibits pancreatic cancer cells and xenograft pancreatic tumors

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Effects of 12-O-Tetradecanoylphorbol-13-acetate (TPA) in Combination with Paclitaxel (Taxol) on Prostate Cancer LNCaP Cells Cultured In vitro or Grown as Xenograft Tumors in Immunodeficient Mice

Cited by 24 publications

References 25 publications

123I-MIP-1072, a Small-Molecule Inhibitor of Prostate-Specific Membrane Antigen, Is Effective at Monitoring Tumor Response to Taxane Therapy

123I-MIP-1072, a Small-Molecule Inhibitor of Prostate-Specific Membrane Antigen, Is Effective at Monitoring Tumor Response to Taxane Therapy

Phorbol ester–induced PKCϵ down-modulation sensitizes AML cells to TRAIL-induced apoptosis and cell differentiation

A triple combination of atorvastatin, celecoxib and tipifarnib strongly inhibits pancreatic cancer cells and xenograft pancreatic tumors

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¹²³I-MIP-1072, a Small-Molecule Inhibitor of Prostate-Specific Membrane Antigen, Is Effective at Monitoring Tumor Response to Taxane Therapy

¹²³I-MIP-1072, a Small-Molecule Inhibitor of Prostate-Specific Membrane Antigen, Is Effective at Monitoring Tumor Response to Taxane Therapy