Preclinical Studies of Chemotherapy Using Histone Deacetylase Inhibitors in Endometrial Cancer

Because epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in endometrial cancers, novel compounds endowed with a histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach. In this review, we discuss the biologic and therapeutic effects of HDAC inhibitors (HDACIs) in treating endometrial cancer. HDACIs were able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and the expression of genes related to the malignant phenotype in a variety of endometrial cancer cell lines. Furthermore, HDACIs were able to induce the accumulation of acetylated histones in the chromatin of the p21WAF1 gene in human endometrial carcinoma cells. In xenograft models, some HDACIs have demonstrated antitumor activity with only few side effects. In this review, we discuss the biologic and therapeutic effects of HDACIs in treating endometrial cancer, with a special focus on preclinical studies.

[1]  Jee H Jung,et al.  A natural histone deacetylase inhibitor, Psammaplin A, induces cell cycle arrest and apoptosis in human endometrial cancer cells. , 2008, Gynecologic oncology.

[2]  E. Sausville,et al.  Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphoma. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  Dipali Sharma,et al.  A Novel Histone Deacetylase Inhibitor, Scriptaid, Enhances Expression of Functional Estrogen Receptor α (ER) in ER negative human breast cancer cells in combination with 5-aza 2′-deoxycytidine , 2003, Breast Cancer Research and Treatment.

[4]  Shi-Wen Jiang,et al.  Histone deacetylase inhibitors induce apoptosis in both Type I and Type II endometrial cancer cells. , 2007, Gynecologic oncology.

[5]  S. Bates,et al.  A review of depsipeptide and other histone deacetylase inhibitors in clinical trials. , 2004, Current pharmaceutical design.

[6]  T. Ueda,et al.  Anticancer activity of MS-275, a novel histone deacetylase inhibitor, against human endometrial cancer cells. , 2006, Anticancer research.

[7]  J. Simiand,et al.  Mechanism of anticonvulsant action of valproate , 1982, Progress in Neurobiology.

[8]  R. Blaheta,et al.  Valproate and valproate-analogues: potent tools to fight against cancer. , 2002, Current medicinal chemistry.

[9]  C. Allis,et al.  Translating the Histone Code , 2001, Science.

[10]  G. Perez,et al.  Intrinsic apoptotic and thioredoxin pathways in human prostate cancer cell response to histone deacetylase inhibitor , 2006, Proceedings of the National Academy of Sciences.

[11]  H. Koeffler,et al.  Histone Deacetylase Inhibitors Have a Profound Antigrowth Activity in Endometrial Cancer Cells , 2004, Clinical Cancer Research.

[12]  T. Ueda,et al.  M344 is a novel synthesized histone deacetylase inhibitor that induces growth inhibition, cell cycle arrest, and apoptosis in human endometrial cancer and ovarian cancer cells. , 2006, Gynecologic oncology.

[13]  Jessica E. Bolden,et al.  Anticancer activities of histone deacetylase inhibitors , 2006, Nature Reviews Drug Discovery.

[14]  T. Ueda,et al.  Apicidin, a novel histone deacetylase inhibitor, has profound anti-growth activity in human endometrial and ovarian cancer cells. , 2007, International journal of molecular medicine.

[15]  P. Marks,et al.  A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Phillip Crews,et al.  Psammaplins from the sponge Pseudoceratina purpurea: inhibition of both histone deacetylase and DNA methyltransferase. , 2003, The Journal of organic chemistry.

[17]  D. Marchion,et al.  Development of histone deacetylase inhibitors for cancer treatment , 2007, Expert review of anticancer therapy.

[18]  E. Sausville,et al.  FR901228 causes mitotic arrest but does not alter microtubule polymerization , 2000, Anti-cancer drugs.

[19]  R A Rifkind,et al.  Second generation hybrid polar compounds are potent inducers of transformed cell differentiation. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[20]  P. Pandolfi,et al.  Therapeutic targeting of transcription in acute promyelocytic leukemia by use of an inhibitor of histone deacetylase. , 1998, Journal of the National Cancer Institute.

[21]  S. Horiuchi,et al.  Sodium butyrate induces growth arrest and senescence‐like phenotypes in gynecologic cancer cells , 2001, International journal of cancer.

[22]  D M Schmatz,et al.  Apicidin: a novel antiprotozoal agent that inhibits parasite histone deacetylase. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[23]  E. Olson,et al.  The many roles of histone deacetylases in development and physiology: implications for disease and therapy , 2009, Nature Reviews Genetics.

[24]  E. Sausville,et al.  MS-275, a histone deacetylase inhibitor, selectively induces transforming growth factor beta type II receptor expression in human breast cancer cells. , 2001, Cancer research.

[25]  T. Tsuruo,et al.  A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[26]  T. Ueda,et al.  RETRACTED: M344 is a novel synthesized histone deacetylase inhibitor that induces growth inhibition, cell cycle arrest, and apoptosis in human endometrial cancer and ovarian cancer cells , 2006 .

[27]  R. Reeves,et al.  Sodium butyrate inhibits histone deacetylation in cultured cells , 1978, Cell.

[28]  S. Modesitt,et al.  A phase II study of vorinostat in the treatment of persistent or recurrent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group study. , 2008, Gynecologic oncology.

[29]  D. Bernhard,et al.  The histone deacetylase inhibitor and chemotherapeutic agent suberoylanilide hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of Bid and production of reactive oxygen species , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[30]  H. W. Lee,et al.  Apicidin, a histone deacetylase inhibitor, inhibits proliferation of tumor cells via induction of p21WAF1/Cip1 and gelsolin. , 2000, Cancer research.

[31]  L. Ngo,et al.  Histone deacetylase (HDAC) inhibitor activation of p21WAF1 involves changes in promoter-associated proteins, including HDAC1. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[32]  K. Nagashima,et al.  A new antifungal antibiotic, trichostatin. , 1976, The Journal of antibiotics.

[33]  K. Kang,et al.  Mechanism of apicidin-induced cell cycle arrest and apoptosis in Ishikawa human endometrial cancer cells. , 2009, Chemico-biological interactions.

[34]  T. Ueda,et al.  A novel histone deacetylase inhibitor, Scriptaid, induces growth inhibition, cell cycle arrest and apoptosis in human endometrial cancer and ovarian cancer cells. , 2006, International journal of molecular medicine.

[35]  N. Kawamata,et al.  Human ovarian carcinoma cells: Histone deacetylase inhibitors exhibit antiproliferative activity and potently induce apoptosis , 2004, Cancer.

[36]  N. Tsuji,et al.  Trichostatin C, a glucopyranosyl hydroxamate. , 1978, The Journal of antibiotics.

[37]  S. Kern,et al.  A novel histone deacetylase inhibitor identified by high-throughput transcriptional screening of a compound library. , 2000, Cancer research.

[38]  M. Malkin,et al.  Phase I dose escalation clinical trial of phenylbutyrate sodium administered twice daily to patients with advanced solid tumors , 2006, Investigational New Drugs.

[39]  C. Van Lint,et al.  The expression of a small fraction of cellular genes is changed in response to histone hyperacetylation. , 1996, Gene expression.

[40]  T. Suzuki,et al.  Synthesis and histone deacetylase inhibitory activity of new benzamide derivatives. , 1999, Journal of medicinal chemistry.

[41]  S. Horinouchi,et al.  Oxamflatin is a novel antitumor compound that inhibits mammalian histone deacetylase , 1999, Oncogene.

[42]  Jorge A. Almenara,et al.  The histone deacetylase inhibitor MS-275 promotes differentiation or apoptosis in human leukemia cells through a process regulated by generation of reactive oxygen species and induction of p21CIP1/WAF1 1. , 2003, Cancer research.

[43]  G Brosch,et al.  Amide analogues of trichostatin A as inhibitors of histone deacetylase and inducers of terminal cell differentiation. , 1999, Journal of medicinal chemistry.

[44]  P. Marks,et al.  Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors , 1999, Nature.

[45]  C. Allis,et al.  The language of covalent histone modifications , 2000, Nature.

[46]  M. Nishida.  The Ishikawa cells from birth to the present , 2002, Human Cell.

[47]  K. Sugita,et al.  Oxamflatin: a novel compound which reverses malignant phenotype to normal one via induction of JunD. , 1996, Oncogene.

[48]  N. Takai,et al.  Human endometrial and ovarian cancer cells: histone deacetylase inhibitors exhibit antiproliferative activity, potently induce cell cycle arrest, and stimulate apoptosis. , 2007, Current medicinal chemistry.

[49]  M. Guenther,et al.  Histone Deacetylase Is a Direct Target of Valproic Acid, a Potent Anticonvulsant, Mood Stabilizer, and Teratogen* , 2001, The Journal of Biological Chemistry.

[50]  Shi-Wen Jiang,et al.  Histone deacetylase inhibitors and paclitaxel cause synergistic effects on apoptosis and microtubule stabilization in papillary serous endometrial cancer cells , 2006, Molecular Cancer Therapeutics.

[51]  T. Ueda,et al.  CBHA Is a Family of Hybrid Polar Compounds That Inhibit Histone Deacetylase, and Induces Growth Inhibition, Cell Cycle Arrest and Apoptosis in Human Endometrial and Ovarian Cancer Cells , 2006, Oncology.

[52]  D. Miller,et al.  Pharmacotherapy of endometrial cancer , 2009, Expert opinion on pharmacotherapy.