HPV-mediated nuclear export of HP1γ drives cervical tumorigenesis by downregulation of p53.

E6 oncoprotein derived from high-risk human papillomavirus (HPV) drives the development of cervical cancer through p53 degradation. Because cervical cancer therapies to inactivate HPV or E6 protein are not available, alternative strategies are required. Here, we show that HPV-mediated nuclear export of human heterochromatin protein 1γ (HP1γ) reduces the stability of p53 through UBE2L3-mediated p53 polyubiquitination during cervical cancer progression. In general, HP1 plays a key role in heterochromatin formation and transcription in the nucleus. However, our immunostaining data showed that the majority of HP1γ is localized in the cytoplasm in HPV-mediated cervical cancer. We found that HPV E6 protein drives unusual nuclear export of HP1γ through the interaction between the NES sequence of HP1γ and exportin-1. The mutation of the NES sequence in HP1γ led to nuclear retention of HP1γ and reduced cervical cancer cell growth and tumor generation. We further discovered that HP1γ directly suppresses the expression of UBE2L3 which drives E6-mediated proteasomal degradation of p53 in cervical cancer. Downregulation of UBE2L3 by overexpression of HP1γ suppressed UBE2L3-dependent p53 degradation-promoting apoptosis of cervical cancer cells. Our findings propose a useful strategy to overcome p53 degradation in cervical cancer through the blockage of nuclear export of HP1γ.

HDAC6­selective inhibitor synergistically enhances the anticancer activity of immunomodulatory drugs in multiple myeloma.

Nonselective histone deacetylase (HDAC) inhibitors have therapeutic effects, but exhibit dose­limiting toxicities in patients with multiple myeloma (MM). The present study investigated the interaction between the HDAC6 inhibitor, A452, and immunomodulatory drugs (IMiDs) on dexamethasone (Dex)­sensitive and ­resistant MM cells compared with the current clinically tested HDAC6 inhibitor, ACY­1215. It was shown that the combination of the HDAC6­selective inhibitor, A452, with either of the IMiDs tested (lenalidomide or pomalidomide) led to the synergistic inhibition of cell growth, a decrease in the viability of MM cells and in an increase in the levels of apoptosis. Furthermore, enhanced cell death was associated with the inactivation of AKT and extracellular signal­regulated kinase (ERK)1/2. Of note, A452 in combination with IMiDs induced synergistic MM cytotoxicity without altering the expression of cereblon and thereby, the synergistic downregulation of IKAROS family zinc finger (IKZF)1/3, c­Myc and interferon regulatory factor 4 (IRF4). Furthermore, combined treatment with A452 and IMiDs induced the synergistic upregulation of PD­L1. More importantly, this combination treatment was effective in the Dex­resistant MM cells. Overall, the findings of this study indicate that A452 is more effective as an anticancer agent than ACY­1215. Taken together, these findings suggest that a combination of the HDAC6­selective inhibitor, A452, and IMiDs may prove to be beneficial in the treatment of patients with MM.

Comparison of three heterochromatin protein 1 homologs in Drosophila.

Heterochromatin protein 1 (HP1) is an epigenetic regulator of chromatin structure and genome function in eukaryotes. Despite shared features, most eukaryotes have a minimum of three HP1 homologs with differential localization patterns and functions. Most studies focus on Drosophila HP1a [also known as Su(var)205], and little is known about the properties of HP1b and HP1c. To determine the features of the three HP1 homologs, we performed the first comprehensive comparative analysis of Drosophila HP1 homologs. HP1 differentially homodimerizes and heterodimerizes in vivo and in vitro HP1b and HP1c, but not HP1a, are localized to both the nucleus and cytoplasm. The C-terminal extension region (CTE) targets HP1c and HP1b to the cytoplasm. Biochemical approaches show that HP1 binds to various interacting partners with different binding affinities. Each HP1 associates differently with RNA polymerase II; a gene reporter assay revealed that HP1a and HP1b, but not HP1c, inhibit transcriptional activity, suggesting that HP1c serves as a positive regulator in transcription. Thus, these studies provide the basic clues pertaining to the molecular mechanism by which HP1 might control cellular processes in a homolog-specific manner.

A452, an HDAC6-selective inhibitor, synergistically enhances the anticancer activity of chemotherapeutic agents in colorectal cancer cells.

Although histone deacetylase inhibitors (HDACi) alone could be clinically useful, these are most recently used in combination with other anticancer agents in clinical trials for cancer treatment. Recently, we reported the anticancer activity of an HDAC6-selective inhibitor A452 toward various cancer cell types. This study aims to present a potent synergistic antiproliferative effect of A452/anticancer agent treatment in colorectal cancer cells (CRC) cells, independently of the p53 status. A452 in combination with irinotecan, or SAHA is more potent than either drug alone in the apoptotic pathway as evidenced by activated caspase-3 and PARP, increased Bak and pp38, decreased Bcl-xL, pERK, and pAKT, and induced apoptotic cells. Furthermore, A452 enhances DNA damage induced by anticancer agents as indicated by the increased accumulation of γH2AX and the activation of the checkpoint kinase Chk2. The silencing of HDAC6 enhances the cell growth inhibition and cell death caused by anticancer agents. In addition, A452 induces the synergistic suppression of cell migration and invasion. This study suggests a mechanism by which HDAC6-selective inhibition can enhance the efficacy of specific anticancer agents in CRC cells.

The HDAC6 inhibitor ACY­1215 enhances the anticancer activity of oxaliplatin in colorectal cancer cells.

ACY­1215, also known as ricolinostat, is a leading histone deacetylase 6 inhibitor, which is currently being tested in clinical trials for hematological malignancies. Previous studies have reported that ACY­1215 is not potent enough as a monotherapy for the treatment of colorectal cancer (CRC), which generally requires combination therapy for successful treatment. Therefore, the present study aimed to determine whether the synergistic interaction detected between ACY­1215 and anticancer agents in hematological cancers could occur in solid tumors. The results of the present study indicated that ACY­1215 exerted a potent synergistic anti-proliferative effect when used in combination with anticancer agents in CRC cells. The combination of ACY­1215 and oxaliplatin was more potent than either drug alone, as indicated by an increase in apoptotic cells and their effects on the apoptotic pathway; ACY­1215 and oxaliplatin cotreatment activated caspase­3 and poly (ADP ribose) polymerase, increased B­cell lymphoma (Bcl)­2 homologous antagonist/killer expression, and decreased Bcl­extra large protein, phosphorylated-extracellular signal-regulated kinase and phosphorylated-protein kinase B expression. In addition, combined treatment of ACY­1215 and anticancer agents induced synergistic upregulation of programmed death­ligand 1. These findings suggested that a therapeutic strategy that combines ACY­1215 and oxaliplatin warrants attention for the treatment of solid tumors, including CRC.

A potent hydroxamic acid-based, small-molecule inhibitor A452 preferentially inhibits HDAC6 activity and induces cytotoxicity toward cancer cells irrespective of p53 status.

HDAC6-selective inhibitors are novel epigenetic anticancer agents. However, their precise mechanisms of action are incompletely understood. We investigated the anticancer mechanisms of the novel potent and selective HDAC6 inhibitor A452 compared with current clinically tested HDAC6 inhibitor ACY-1215. We demonstrate that A452 effectively inhibits the cell growth and viability of various cancer cell types, irrespective of p53 status. A452-induced apoptosis as evidenced by activated caspase 3 and PARP, increased Bak and Bax and decreased Bcl-xL. Moreover, A452 shifted cells away from antiapoptotic (AKT and ERK) pathways and toward proapoptotic (p38) pathways. A452 triggered DNA damage via increased γH2AX and activation of the checkpoint kinase Chk2. A452 induced the suppression of cell migration and invasion. Interestingly, A452 upregulated the expression of PD-L1, which regulates the PD-1 inhibitory pathway in T cells. Overall, our results suggest that A452 is more effective as an anticancer agent than ACY-1215. Therefore, therapeutically targeting HDAC6 may represent a novel strategy for cancer treatment irrespective of the p53 mutation status.

HDAC6 deacetylates p53 at lysines 381/382 and differentially coordinates p53-induced apoptosis.

HDAC6-selective inhibitors represent promising new cancer therapeutic agents, but their precise mechanisms of action are not well understood. In particular, p53's role in HDAC6 inhibitor-induced effects has not been fully elucidated. In this study, we show that an HDAC6-selective inhibitor, A452, increased wild-type p53 levels by destabilizing MDM2, but decreased mutant p53 by inducing MDM2 and inhibiting Hsp90-mutant p53 complex formation. Interestingly, HDAC6 levels inversely correlated with p53 acetylation at lysines 381/382 associated with p53 functional activation. A452 blocked HDAC6 nuclear localization, resulting in increased levels of acetylated p53 at Lys381/382. HDAC6 bound to the C-terminal region of p53 via its deacetylase domain. A452 disrupted the HDAC6-Hsp90 chaperone machinery via Hsp90 acetylation and degradation. Furthermore, it chemosensitized cancer cells to the Hsp90 inhibitor 17-AAG. Overall, silencing of HDAC6 showed similar effects. These findings suggest that the anticancer action of HDAC6 inhibitors requires p53 and Hsp90 and targeting of HDAC6 may represent a new therapeutic strategy for cancers regardless of p53's mutation status.

Advances in epigenetic glioblastoma therapy.

Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults despite contemporary gold-standard first-line treatment strategies. This type of tumor recurs in virtually all patients and no commonly accepted standard treatment exists for the recurrent disease. Therefore, advances in all scientific and clinical aspects of GBM are urgently needed. Epigenetic mechanisms are one of the major factors contributing to the pathogenesis of cancers, including glioblastoma. Epigenetic modulators that regulate gene expression by altering the epigenome and non-histone proteins are being exploited as therapeutic drug targets. Over the last decade, numerous preclinical and clinical studies on histone deacetylase (HDAC) inhibitors have shown promising results in various cancers. This article provides an overview of the anticancer mechanisms of HDAC inhibitors and the role of HDAC isoforms in GBM. We also summarize current knowledge on HDAC inhibitors on the basis of preclinical studies and emerging clinical data.

HDAC6 regulates sensitivity to cell death in response to stress and post-stress recovery.

Histone deacetylase 6 (HDAC6) plays an important role in stress responses such as misfolded protein-induced aggresomes, autophagy, and stress granules. However, precisely how HDAC6 manages response during and after cellular stress remains largely unknown. This study aimed to investigate the effect of HDAC6 on various stress and post-stress recovery responses. We showed that HIF-1α protein levels were reduced in HDAC6 knockout (KO) MEFs compared to wild-type (WT) MEFs in hypoxia. Furthermore, under hypoxia, HIF-1α levels were also reduced following rescue with either a catalytically inactive or a ubiqiutin-binding mutant HDAC6. HDAC6 deacetylated and upregulated the stability of HIF-1α, leading to activation of HIF-1α function under hypoxia. Notably, both the deacetylase and ubiquitin-binding activities of HDAC6 contributed to HIF-1α stabilization, but only deacetylase activity was required for HIF-1α transcriptional activity. Suppression of HDAC6 enhanced the interaction between HIF-1α and HSP70 under hypoxic conditions. In addition to hypoxia, depletion of HDAC6 caused hypersensitivity to cell death during oxidative stress and post-stress recovery. However, HDAC6 depletion had no effect on cell death in response to heat shock or ionizing radiation. Overall, our data suggest that HDAC6 may serve as a critical stress regulator in response to different cellular stresses.

Influence of toxicologically relevant metals on human epigenetic regulation.

Environmental toxicants such as toxic metals can alter epigenetic regulatory features such as DNA methylation, histone modification, and non-coding RNA expression. Heavy metals influence gene expression by epigenetic mechanisms and by directly binding to various metal response elements in the target gene promoters. Given the role of epigenetic alterations in regulating genes, there is potential for the integration of toxic metal-induced epigenetic alterations as informative factors in the risk assessment process. Here, we focus on recent advances in understanding epigenetic changes, gene expression, and biological effects induced by toxic metals.

Aceroside VIII is a new natural selective HDAC6 inhibitor that synergistically enhances the anticancer activity of HDAC inhibitor in HT29 cells.

The identification of new isoform-specific histone deacetylase inhibitors is important for revealing the biological functions of individual histone deacetylase and for determining their potential use as therapeutic agents. Among the 11 zinc-dependent histone deacetylases that have been identified in humans, histone deacetylase 6 is a structurally and functionally unique enzyme. Here, we tested the inhibitory activity of diarylheptanoids isolated from Betula platyphylla against histone deacetylase 6. Aceroside VIII selectively inhibited histone deacetylase 6 catalytic activity and the combined treatment of aceroside VIII or (-)-centrolobol with A452, another selective histone deacetylase 6 inhibitor, led to a synergistic increase in levels of acetylated α-tubulin. Aceroside VIII, paltyphyllone, and (-)-centrolobol synergistically enhanced the induction of apoptosis and growth inhibition by A452. Consistent with these results, A452 in combination with aceroside VIII, paltyphyllone, or (-)-centrolobol was more potent than either drug alone for the induction of apoptosis. Together, these findings indicate that aceroside VIII is a specific histone deacetylase 6 inhibitor and points to a mechanism by which natural histone deacetylase 6-selective inhibitors may enhance the efficacy of other histone deacetylase 6 inhibitors in colon cancer cells.

HP1ß suppresses metastasis of human cancer cells by decreasing the expression and activation of MMP2.

Heterochromatin protein 1 (HP1) is an epigenetic modifier of gene regulation and chromatin packing via binding to trimethylated histone H3 lysine 9 (H3K9). HP1 plays an important role in gene activation as well as gene repression in heterochromatin and euchromatin. However, the role of individual HP1 proteins in human diseases remains elusive. Here, we show that HP1ß negatively regulates the expression and activation of matrix metallopeptidase (MMP)2, which mediates cancer metastasis by destructing type Ⅳ collagen. Reduced HP1ß expression correlates with the increased level of pro- and active-MMP2 in colon cancer cells. Consistently, HP1ß knockdown (KD) increased and HP1ß overexpression decreased the mRNA level of MMP2 and membrane type 1 metallopeptidase (MT1-MMP). Furthermore, cancer cells overexpressing HP1ß showed impaired migratory ability, whereas HP1ß­deleted cancer cells had increased migration. HP1ß negatively regulates MMP2 expression in a transcriptional level and prevents MMP2 activation through reducing the expression of MT1­MMP. These findings shed new light on HP1ß as a molecular regulator and an efficient therapeutic target of metastatic cancer.

Analysis of the heterochromatin protein 1 (HP1) interactome in Drosophila.

Heterochromatin protein 1 (HP1) was first described in Drosophila melanogaster as a heterochromatin associated protein required for epigenetic gene silencing. Most eukaryotes have at least three HP1 homologs that play differential roles in heterochromatin and euchromatin. However, despite the fact that the three HP1 proteins bind to different regions of the genome, several studies show that most of the interactions occur in a manner specific to HP1a. In addition, little is known about the overall interaction network of the three Drosophila HP1 homologs, HP1a, HP1b, and HP1c. Here, we performed the first comprehensive proteomic analysis of Drosophila HP1 homologs by coupling a double-affinity purification approach with MudPIT analysis to identify interacting proteins of Drosophila HP1. We discovered 160-310 proteins co-eluted with HP1, including a number of novel HP1-binding partners along with the previously identified HP1 binding proteins. Finally, we showed that slight and unique binding preferences might exist between the three HP1 proteins in Drosophila. These studies are the first to systematically analyze the interactome of HP1 paralogs and provide the basic clues as to the molecular mechanism by which HP1 might control cellular processes. BIOLOGICAL SIGNIFICANCE: Most eukaryotes have at least three HP1 homologs with similar domain structures but with differential roles in heterochromatin and euchromatin. However, little is known about the overall interactome of the three Drosophila HP1 homologs, HP1a, HP1b, and HP1c. The present study compared interacting proteins of three HP1 homologs in Drosophila. To better understand the underlying mechanisms for gene regulation of HP1, a double-affinity purification and MudPIT mass spectrometry were employed to identify differential proteins as well as common binding proteins of HP1. Therefore, this study provides not only the comparative proteomic analysis but also molecular mechanism underlying the HP1 homolog-specific function.

Reversine induces multipotency of lineage-committed cells through epigenetic silencing of miR-133a.

Reversine has been shown to induce dedifferentiation of C2C12 murine myoblasts into multipotent progenitor cells. However, little is known about the key regulators mediating the dedifferentiation induced by reversine. Here, we show that large scale miRNA gene expression profiling of reversine-treated C2C12 myoblasts identifies a down-regulated miRNA, miR-133a, involved in dedifferentiation of myoblasts. Reversine treatment results in up- and down-regulated miRNA profiles. Among miRNAs affected by reversine, the level of muscle-specific miR-133a, which has been shown to be up-regulated during muscle development and to suppress differentiation into other lineages, is markedly reduced by treatment of C2C12 myoblasts with reversine. In parallel, reversine decreases the expression and recruitment of myogenic factor, SRF, to the enhancer regions of miR-133a. Sequentially, down-regulation of miR-133a by reversine is accompanied by a decrease in active histone modifications including trimethylation of histone H3K4 and H3K36, phosphorylation of H3S10, and acetylation of H3K14 on the miR-133a promoter, leading to dissociation of RNA polymerase II from the promoter. Furthermore, inhibition of miR-133a by transfection of C2C12 myoblasts with miR-133a inhibitor increases the expression of osteogenic lineage marker, Ogn, and adipotenic lineage marker, ApoE, similar to that in response to reversine. In contrast, the co-overexpression of miR-133a mimic reversed the effect of reversine on C2C12 myoblast dedifferentiation. Taken together, the results indicate that reversine induces a multipotency of C2C12 myoblasts by suppression of miR-133a expression through depletion of active histone modifications, and suggest that miR-133a is a potential miRNA regulating the reversine-induced dedifferentiation. Collectively, our findings provide a mechanistic rationale for the application of reversine to dedifferentiation of somatic cells.

Simulated microgravity contributes to autophagy induction by regulating AMP-activated protein kinase.

Exposure to microgravity is supposed to affect almost all biological systems, and we speculated that microgravity is potentially involved in autophagy regulation. A clinostat was used to simulate microgravity, and HEK293 cells that stably express GFP-LC3 were used for sensitive monitoring of autophagy induction. The clinorotation of GFP-LC3 cells resulted in autophagosome formation in the cytoplasm and a change in autophagosomal marker expression. Autophagy induction was accompanied by phosphorylation of AMPK (Thr 172) and by the dephosphorylation of mammalian target of rapamycin. To elucidate the role of AMPK in microgravity-induced autophagy, we suppressed AMPK expression by knockdown via siRNA, which inhibited the induction of autophagy upon exposure to microgravity. In addition, the clinorotation of C2C12 myotube cells resulted in the enlarged and distinctive LC3 spots in the cytoplasm and AMPK activation. These results indicate that simulated microgravity possibly contributes to autophagy induction by regulating AMPK.

Amurensin G induces autophagy and attenuates cellular toxicities in a rotenone model of Parkinson's disease.

Although Parkinson's disease is a common neurodegenerative disorder its cause is still unknown. Recently, several reports showed that inducers of autophagy attenuate cellular toxicities in Parkinson's disease models. In this report we screened HEK293 cells that stably express GFP-LC3, a marker of autophagy, for autophagy inducers and identified amurensin G, a compound isolated from the wild grape (Vitis amurensis). Amurensin G treatment induced punctate cytoplasmic expression of GFP-LC3 and increased the expression level of endogenous LC3-II. Incubation of human dopaminergic SH-SY5Y cells with amurensin G attenuated the cellular toxicities of rotenone in a model of Parkinson's disease. Amurensin G inhibited rotenone-induced apoptosis and interfered with rotenone-induced G2/M cell cycle arrest. In addition, knockdown of beclin1, a regulator of autophagy, abolished the effect of amurensin G. These data collectively indicate that amurensin G attenuates cellular toxicities through the induction of autophagy.

Bevacizumab eye drops delay corneal epithelial wound healing and increase the stromal response to epithelial injury in rats.

BACKGROUND: To evaluate the effects of bevacizumab eye drops on corneal epithelial wound healing and the stromal response after epithelial injury in rats. METHODS: We divided 160 Sprague-Dawley male rats into two groups and de-epithelized corneas with a microblade. Five percent bevacizumab (Avastin) and antibiotic (Cravit) eyedrops were treated four times daily in the bevacizumab group and antibiotic eye drops only in the control group. Wound area evaluation, enzyme-linked immunosorbent assay, immunofluorescent staining, and real-time polymerase chain reaction were performed with rat corneas. RESULTS: The percentage of wound healing in the bevacizumab group was lower than in the control group at 24, 48 and 72 hours after epithelial debridement (P = 0.02, 0.01 and 0.01). Corneal matrix metalloproteinase-2 (P = 0.02, 0.01 and 0.02), matrix metalloproteinase-9 (P = 0.03, 0.01 and 0.01) and transforming growth factor-ß (P = 0.02, 0.02 and 0.01) proteins in the bevacizumab group were higher than control group at 24, 48, and 72 hours. Matrix metalloproteinase-2, matrix metalloproteinase-9, transforming growth factor-b and a-smooth muscle actin were strongly stained in the bevacizumab corneas compared with control corneas in immunofluorescent staining. Matrix metalloproteinase-2 (P = 0.04, 0.03 and 0.04), matrix metalloproteinase- 9 (P = 0.03, 0.01 and 0.02), transforming growth factor-b (P = 0.03, 0.03 and 0.03) and a-smooth muscle actin (P = 0.04, 0.01 and 0.04) messenger RNA levels in the bevacizumab group were also highly expressed compared with the control group at 24, 48, and 72 hours. CONCLUSIONS: The bevacizumab eye drops delay the wound healing and increase stromal response after corneal epithelial injury in rats.

One-year results of intravitreal ranibizumab with or without photodynamic therapy for polypoidal choroidal vasculopathy.

PURPOSE: To evaluate the safety and efficacy of intravitreal ranibizumab with or without photodynamic therapy (PDT) in the treatment of polypoidal choroidal vasculopathy (PCV) in Korean patients. METHODS: A retrospective chart review of 22 patients (24 eyes) with PCV was conducted. Nine eyes were treated with intravitreal ranibizumab combined with a single session of PDT (group 1), and 15 eyes were treated only with ranibizumab (group 2). Such clinical evaluations as best-corrected Snellen visual acuity, central retinal thickness (CRT) by optical coherence tomography (OCT), fluorescein angiography (FA) and indocyanine green angiography (ICGA) were done at baseline, 1, 3, 6, 9 and 12 months after the first injections. Ranibizumab was reinjected on an as-needed basis guided by OCT, FA and ICGA, or at the doctor's discretion. RESULTS: The mean follow-up duration was 22.5 months (range 12-37). The mean best-corrected visual acuity (logMAR) improved, and the mean CRT decreased throughout 12 months in both groups; no statistically significant difference between the groups was found (p = 0.327, p = 0.073, respectively). The number of ranibizumab injections was not significantly different either (p = 0.555). CONCLUSIONS: Intravitreal ranibizumab with or without PDT for PCV in Korean patients resulted in visual and anatomical improvement over the 1-year follow-up period.

The role of heme oxygenase-1 in the proliferation and odontoblastic differentiation of human dental pulp cells.

INTRODUCTION: It was recently reported that heme oxygenase-1 (HO-1) activity is related to stem cell differentiation; however, the involvement of HO-1 in pulp cell growth and differentiation has not been well explored. The purpose of this study was to investigate the role of HO-1 in the growth and differentiation of human dental pulp cells (HDPCs). METHODS: We evaluated cell growth by MTT assay, mineralization by alizarin red staining, and differentiation marker mRNA expression by reverse transcriptase polymerase chain reaction. RESULTS: HO-1 induction by cobaltic protoporphyrin IX (CoPP) in HDPCs increased cell growth and mineralization and up-regulated the messenger RNA expression of such odontoblastic markers as alkaline phosphatase, osteopontin, bone sialoprotein, dentin matrix protein-1, and dentin sialophosphoprotein. Carbon monoxide scavenger, iron chelator, HO-1 inhibitor, and HO-1 small interfering RNA (siRNA) attenuated HDPC growth and differentiation. CONCLUSIONS: CoPP treatment results in dental pulp cell proliferation and odontoblast differentiation that appears partly mediated by HO-1. Our results suggest that odontoblastic differentiation and growth are positively regulated by HO-1 induction and negatively regulated by HO-1 inhibition. Thus, pharmacologic HO-1 induction might represent a potent therapeutic approach for pulp capping and the regeneration of HDPCs.

A comparison of the efficacy of cataract surgery using Aqualase with phacoemulsification using MicroFlow system.

PURPOSE: To compare the outcomes after phacoemulsification performed with the AquaLase and phacoemulsification in MicroFlow system, including surgically induced astigmatism (SIA), corneal endothelial cell damage and postoperative recovery of visual acuity. METHODS: The cataracts of Lens Opacities Classification System, version III (LOCS III) nuclear grade below 2 were subjected in this study. Nineteen eyes underwent cataract operation using AquaLase (Alcon Laboratories, Fort Worth, Texas, U.S.A.). A control group (19 eyes) used the MicroFlow system (Millenium, Stortz, U.S.A.) and was selected by matching age, sex, systemic disease, corneal astigmatism and corneal endothelial cell density. All the surgeries were performed by the same operator. SIA, corneal endothelial cell loss, visual acuity, and corneal thickness were evaluated postoperatively. RESULTS: SIA in the group using AquaLase was less than that of the group using MicroFlow system (P=0.022) at 2 months postoperatively. Evaluation of corneal endothelial cell loss, recovery of visual acuity and corneal thickness found no statistically significant differences between the two groups. CONCLUSIONS: Cataract surgery using AquaLase induces less surgically induced astigmatism in mild to moderate cataracts.