Enhancement of cisplatin induced apoptosis by suberoylanilide hydroxamic acid in human oral squamous cell carcinoma cell lines

Shen, Jun; Huang, Canhua; Jiang, Lu; Gao, Feng; Wang, Zhi; Zhang, Yuanyuan; Bai, Jingping; Zhou, Hongmei; Chen, Qianming

doi:10.1016/j.bcp.2007.03.009

Cited by 78 publications

(70 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…p53 has been implicated in SAHA-induced apoptosis in cancer cells (Henderson et al, 2003;Shen et al, 2007). In renal cells, p53 has a role in acute kidney injury induced by ischemia as well as cisplatin (Cummings and Schnellmann, 2002;Kelly et al, 2003;Jiang et al, 2004).…”

Section: Downloaded Frommentioning

confidence: 99%

Induction of Apoptosis in Renal Tubular Cells by Histone Deacetylase Inhibitors, a Family of Anticancer Agents

Dong

Wang

et al. 2008

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Inhibitors of histone deacetylases, including suberoylanilide hydroxamic acid (SAHA) and Trichostatin A, are a new class of anticancer agents. With potent chemotherapy effects in cancers, these agents are not obviously toxic in normal nonmalignant cells or tissues. However, their toxicity in kidney cells has not been carefully evaluated. Here, we demonstrate a potent apoptosis-inducing activity of SAHA in cultured renal proximal tubular cells. SAHA induces apoptosis at low micromolar concentrations. At 5 M, SAHA induces 30 to ϳ40% apoptosis in 18 h. The apoptosis is accompanied by notable caspase activation; however, the general caspase inhibitor VAD can only partially suppress SAHA-induced apoptosis, suggesting the involvement of both caspase-dependent and -independent mechanisms. SAHA treatment leads to cytochrome c release from mitochondria, which is suppressed by Bcl-2 but not by VAD. Bcl-2 consistently blocks SAHA-induced apoptosis. During SAHA treatment, Bcl-2 and Bcl-XL decrease, and Bid is proteolytically cleaved, whereas Bax and Bak expression remains constant. Bid cleavage, but not Bcl-2/Bcl-XL decrease, is completely suppressed by VAD. SAHA does not activate p53, and pifithrin-␣ (a pharmacological p53 inhibitor) does not attenuate SAHA-induced apoptosis, negating a role of p53 in SAHA-induced apoptosis. SAHA induces histone acetylation, which is not affected by VAD, Bcl-2, or pifithrin-␣. Trichostatin A can also induce apoptosis and histone acetylation in renal tubular cells. Together, the results have shown evidence for renal toxicity of histone deacetylase inhibitors. The toxicity may be related to protein acetylation and decrease of antiapoptotic proteins including Bcl-2 and Bcl-XL.

show abstract

Section: Downloaded Frommentioning

confidence: 99%

Induction of Apoptosis in Renal Tubular Cells by Histone Deacetylase Inhibitors, a Family of Anticancer Agents

Dong

Wang

et al. 2008

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…In studies of SAHA and Cddp combinatorial use in other tumor cell lines such as oral squamous cell carcinoma and cervical cancer, cytotoxic augmentation was mediated through a multitude of effects (48)(49)(50)(51). For oral squamous cell carcinoma, Shen and colleagues showed that SAHA enhancement of Cddp-mediated apoptosis was brought about by an increased p53 activation, increased in pro-apoptotic BID, release of cytochrome c and activation of caspase-3 (48).…”

Section: Discussionmentioning

confidence: 99%

“…For oral squamous cell carcinoma, Shen and colleagues showed that SAHA enhancement of Cddp-mediated apoptosis was brought about by an increased p53 activation, increased in pro-apoptotic BID, release of cytochrome c and activation of caspase-3 (48). In other separate study in oral squamous cell carcinoma, Rikiishi et al found that chemosensitization of Cddp by SAHA resulted in increased apoptosis via p53-independent activation of the mitochondrial pathway and caspase cascade that was accompanied by a decrease in cellular GSH levels (49).…”

Section: Discussionmentioning

confidence: 99%

Synergistic effects of suberoylanilide hydroxamic acid combined with cisplatin causing cell cycle arrest independent apoptosis in platinum-resistant ovarian cancer cells

et al. 2012

View full text Add to dashboard Cite

Abstract. Histone deacetylase inhibitors (HDACIs) belong to an emerging class of anticancer compounds. It is increasingly recognized that their unique and complementary mode of action make HDACIs valuable agents in augmenting the cytotoxicity of conventional chemotherapeutics. We examined the potential for combined use of an approved HDACI, suberoylanilide hydroxamic acid (SAHA), with cisplatin (Cddp) in platinum-resistant ovarian cancer cells, OVCAR-3 and SKOV-3. The nature of the drug interaction following combinatory therapy was assessed using median effect analysis. We found that SAHA acted synergistically with Cddp over a wide range of concentrations in both cell types, resulting in favorable dose reductions of both compounds. In particular, in the more Cddpresistant SKOV-3 cells, more than 8-fold dose reduction of Cddp was achieved with the simultaneous use of SAHA and Cddp as compared to the dose required to elicit similar cell kill effects using Cddp alone. More importantly, therapeutic selectivity for ovarian cancer cells over normal fibroblast cells were maintained with the combinatorial therapy. We further observed that the augmentation of Cddp-induced cell death was mediated by the net increase in apoptosis and was independent of cell cycle arrest. Overall, concurrent application of SAHA and Cddp yielded the most favorable cell kill, indicating that this combination is promising for treatment of platinum-resistant ovarian tumors.

show abstract

“…Finally the staining was carried out according to the manufacturer's instructions and fluorescence was visualized to count TUNEL-positive cells with Leica DMI 6000B microscope (Leica DMI 6000B, Leica Co., Germany) [16].…”

Section: Tunel Assaymentioning

confidence: 99%

Honokiol: a promising small molecular weight natural agent for the growth inhibition of oral squamous cell carcinoma cells

Chen

Dan

et al. 2011

Int J Oral Sci

View full text Add to dashboard Cite

Enhancement of cisplatin induced apoptosis by suberoylanilide hydroxamic acid in human oral squamous cell carcinoma cell lines

Cited by 78 publications

References 35 publications

Induction of Apoptosis in Renal Tubular Cells by Histone Deacetylase Inhibitors, a Family of Anticancer Agents

Induction of Apoptosis in Renal Tubular Cells by Histone Deacetylase Inhibitors, a Family of Anticancer Agents

Synergistic effects of suberoylanilide hydroxamic acid combined with cisplatin causing cell cycle arrest independent apoptosis in platinum-resistant ovarian cancer cells

Honokiol: a promising small molecular weight natural agent for the growth inhibition of oral squamous cell carcinoma cells

Contact Info

Product

Resources

About