Synergistic anticancer effects of cisplatin and histone deacetylase inhibitors (SAHA and TSA) on cholangiocarcinoma cell lines

Asgar, Md. Ali; Senawong, Gulsiri; Sripa, Banchob; Senawong, Thanaset

doi:10.3892/ijo.2015.3240

Cited by 35 publications

(32 citation statements)

References 39 publications

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“…Although some of these agents often demonstrate more potent antitumor effects than SAHA and romidepsin in preclinical testing, none have thus far demonstrated vastly superior clinical activity, or more favorable toxicity profiles, and accordingly none have yet been registered for clinical use except panobinostat (registered in FDA and EMEA). The antineoplastic effects of SAHA have been observed in various malignancies . In advanced leukemia and myelodysplastic syndrome, SAHA exposure induced significantly lower antileukemia activity than the maximum tolerated dose and inhibited the HDAC activity of peripheral blood and bone marrow blasts .…”

Section: Discussionmentioning

confidence: 99%

“…SAHA and 5‐FU synergistically inhibited the proliferation of hepatocellular carcinoma cells by inducing G 0 /G 1 arrest and caspase‐dependent apoptosis . Cisplatin and SAHA dose dependently and synergistically reduced the viability of cholangiocarcinoma cells and induced cell apoptosis, accompanied by upregulation of p53 and p21 and downregulation of CDK4 and Bcl‐2 …”

Section: Discussionmentioning

confidence: 99%

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ING5‐mediated antineuroblastoma effects of suberoylanilide hydroxamic acid

Jiang

Yang

et al. 2018

Cancer Medicine

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Neuroblastoma is the most common extracranial solid neuroendocrine cancer and is one of the leading causes of death in children. To improve clinical outcomes and prognosis, discovering new promising drugs and targeted medicine is essential. We found that applying Suberoylanilide hydroxamic acid (SAHA; Vorinostat, a histone deacetylase inhibitor) and MG132 (a proteasome inhibitor) to SH‐SY5Y cells synergistically suppressed proliferation, glucose metabolism, migration, and invasion and induced apoptosis and cell cycle arrest. These effects occurred both concentration and time dependently and were associated with the effects observed with inhibitor of growth 5 (ING5) overexpression. SAHA and MG132 treatment increased the expression levels of ING5, PTEN, p53, Caspase‐3, Bax, p21, and p27 but decreased the expression levels of 14‐3‐3, MMP‐2, MMP‐9, ADFP, Nanog, c‐myc, CyclinD1, CyclinB1, and Cdc25c concentration dependently, similar to ING5. SAHA may downregulate miR‐543 and miR‐196‐b expression to enhance the translation of ING5 protein, which promotes acetylation of histones H3 and H4. All three proteins (ING5 and acetylated histones H3 and H4) were recruited to the promoters of c‐myc, Nanog, CyclinD1, p21, and p27 for complex formation, thereby regulating the mRNA expression of downstream genes. ING5 overexpression and SAHA and/or MG132 administration inhibited tumor growth in SH‐SY5Y cells by suppressing proliferation and inducing apoptosis. The expression of acetylated histones H3 and ING5 may be closely linked to the tumor size of neuroblastomas. In summary, SAHA and/or MG132 can synergistically suppress the malignant phenotypes of neuroblastoma cells through the miRNA‐ING5‐histone acetylation axis and via proteasomal degradation, respectively. Therefore, the two drugs may serve as potential treatments for neuroblastoma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

ING5‐mediated antineuroblastoma effects of suberoylanilide hydroxamic acid

Jiang

Yang

et al. 2018

Cancer Medicine

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“…HDAC inhibitors including TSA, SAHA and VPA were reported to show synergistic effects by pre-or cotreatment with anticancer drugs. 11,[20][21][22][23][24] The difference in the most significant combination between VPA and TSA/SAHA is not clear, but the differences in the proteome and acetylome profiling between SAHA and VPA might contribute. 25) TSA, SAHA and VPA are all HDAC inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Different Schedule-Dependent Effects of Epigenetic Modifiers on Cytotoxicity by Anticancer Drugs in Colorectal Cancer Cells

Hosokawa

Tanaka

Iwakawa

2017

Biological & Pharmaceutical Bulletin

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Limited information is currently available on how to apply epigenetic modifiers to current colorectal cancer (CRC) chemotherapy. The purpose of this study is to clarify the schedule-dependent effects of combined treatment with conventional anticancer drugs and epigenetic modifiers in human CRC cells. Cytotoxicity in 4 CRC cell lines (SW480, HT29, SW48, and HCT116) was measured using the WST-8 assay. As epigenetic modifiers, 3 DNA methyltransferase (DNMT) inhibitors such as decitabine (DAC), azacytidine (AC), and zebularine (Zeb), and 3 histone deacetylase (HDAC) inhibitors including trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), and valproic acid (VPA) were used. Combination effects were analyzed by the isobologram method. SW480 cells showed the lowest sensitivity to the anticancer drugs 5-fluorouracil, SN-38 (the active form of irinotecan), and oxaliplatin. In SW480 cells, epigenetic modifiers other than VPA showed the most significant synergistic effects when used before anticancer drugs, while VPA showed synergistic effects in co-or post-treatment. In the 3 other CRC cells, synergistic effects were less frequent and weaker. The dose of anticancer drugs may be reduced by combining epigenetic modifiers in SW480 cells, which are less sensitive to anticancer drugs, unlike the more sensitive HT29, SW48, and HCT116 cell lines. These results provide useful information for understanding how to incorporate epigenetic modifiers into current CRC chemotherapy.Key words schedule-dependent treatment; epigenetic therapy; colorectal cancer; DNA methyltransferase inhibitor; histone deacetylase inhibitor Epigenetic alterations such as DNA methylation and histone modifications have been identified as a crucial driving force in the initiation and progression of cancer.1) Since epigenetic alterations are reversible, epigenetic modifiers may be beneficial in chemotherapy.2) Several epigenetic modifiers including DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors have been approved by U.S. Food and Drug Administration (FDA) for the treatment of cancer.Combined chemotherapy, including 5-fluorouracil (5-FU) and either irinotecan (CPT-11) or oxaliplatin (L-OHP), has improved the survival period of metastatic colorectal cancer (CRC). However, resistance to these anticancer drugs, which limits the effectiveness of chemotherapy, has been reported. 3,4) In order to overcome this issue, novel combination therapy using epigenetic modifiers is expected. Clinical trials on combination therapy have been performed using solid tumors including CRC.5,6) However, there is not enough integrated information on how to apply epigenetic modifiers to current CRC chemotherapy. We previously reported that a co-treatment with decitabine (DAC, 5-aza-2′-deoxycytidine), a DNMT inhibitor, and L-OHP exerted the most potent synergistic effects among the combinations tested using 5 epigenetic modifiers and 5-FU, CPT-11, or L-OHP in 4 different CRC cell lines. 7)The treatment schedule is important for effective cancer ...

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“…Cisplatin, 5-fluorouracil, epirubicin, leucovorin, mitomycin-C and gemcitabine either alone or in combination have been used to treat CCA [6, 7]. The first line chemotherapy for advanced CCA is the combination of gemcitabine and cisplatin [1, 8, 9].…”

Section: Introductionmentioning

confidence: 99%

“…The first line chemotherapy for advanced CCA is the combination of gemcitabine and cisplatin [1, 8, 9]. The major drawbacks in clinical applications of cisplatin are the development of resistance by tumors and adverse side effect [7, 10, 11]. Despite intensified evaluation of other chemotherapy combinations with fluorouracil, oxaliplatin or irinotecan, the improvement in survival of CCA patients has been marginal [1, 12].…”

Section: Introductionmentioning

confidence: 99%

Synergistic antitumor activity of the combination of salubrinal and rapamycin against human cholangiocarcinoma cells

et al. 2016

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Less is known about the roles of eukaryotic initiation factor alpha (eIF2α) in cholangiocarcinoma (CCA). Here, we report that eIF2α inhibitor salubrinal inhibits the proliferation of human CCA cells. Clinical application of mammalian target of rapamycin (mTOR) inhibitors only has moderate antitumor efficacy. Therefore, combination approaches may be required for effective clinical use of mTOR inhibitors. Here, we investigated the efficacy of the combination of salubrinal and rapamycin in the treatment of CCA. Our data demonstrate a synergistic antitumor effect of the combination of salubrinal and rapamycin against CCA cells. Rapamycin significantly inhibits the proliferation of CCA cells. However, rapamycin initiates a negative feedback activation of Akt. Inhibition of Akt by salubrinal potentiates the efficacy of rapamycin both in vitro and in vivo. Additionally, rapamycin treatment results in the up-regulation of Bcl-xL in a xenograft mouse model. It is notable that salubrinal inhibits rapamycin-induced Bcl-xL up-regulation in vivo. Taken together, our data suggest that salubrinal and rapamycin combination might be a new and effective strategy for the treatment of CCA.

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Synergistic anticancer effects of cisplatin and histone deacetylase inhibitors (SAHA and TSA) on cholangiocarcinoma cell lines

Cited by 35 publications

References 39 publications

ING5‐mediated antineuroblastoma effects of suberoylanilide hydroxamic acid

ING5‐mediated antineuroblastoma effects of suberoylanilide hydroxamic acid

Different Schedule-Dependent Effects of Epigenetic Modifiers on Cytotoxicity by Anticancer Drugs in Colorectal Cancer Cells

Synergistic antitumor activity of the combination of salubrinal and rapamycin against human cholangiocarcinoma cells

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