Comparative safety profile of bivalent and original COVID-19 mRNA vaccines regarding myocarditis/pericarditis: A pharmacovigilance study.

OBJECTIVES: Bivalent COVID-19 mRNA vaccines, which contain two different components, were authorized to provide protection against both the original strain of SARS-CoV-2 and the Omicron variant as a measure to address the COVID-19 pandemic. Concerns regarding the risk of myocarditis/pericarditis associated with bivalent vaccination have been raised due to the observed superior neutralizing antibody responses. This study aimed to investigate the risk of myocarditis/pericarditis following bivalent COVID-19 mRNA vaccination compared to monovalent vaccination. METHODS: The CDC COVID Data Tracker and the Vaccines Adverse Event Reporting System (VAERS) were analyzed between December 13, 2020 to March 8, 2023. Reporting rates were determined by dividing the number of myocarditis/pericarditis cases by the total number of vaccine doses administered. Disproportionality patterns regarding myocarditis/pericarditis were evaluated for various COVID-19 mRNA vaccinations using reporting odds ratios (RORs). RESULTS: The reporting rate for myocarditis/pericarditis following original monovalent COVID-19 mRNA vaccination was 6.91 (95 % confidence interval [95 %CI] 6.71-7.12) per million doses, while the reporting rate for bivalent vaccination was significantly lower (1.24, 95%CI 0.96-1.58). Disproportionality analysis revealed a higher reporting of myocarditis/pericarditis following original vaccination with a ROR of 2.21 (95 %CI 2.00-2.43), while bivalent COVID-19 mRNA vaccination was associated with fewer reports of myocarditis/pericarditis (ROR 0.57, 95 %CI 0.45-0.72). Sub-analyses based on symptoms, sex, age and manufacturer further supported these findings. CONCLUSION: This population-based study provides evidence that bivalent COVID-19 mRNA vaccination is not associated with risk of myocarditis/pericarditis. These findings provide important insights into the safety profile of bivalent COVID-19 mRNA vaccines and support their continued use as updated boosters.

Major cardiovascular events under biologic psoriasis therapies: a 19-year real-world analysis of FAERS data.

Objective: Over the years when biologic psoriasis therapies (TNF inhibitors, IL-12/23 inhibitors, IL-23 inhibitors, and IL-17 inhibitors) have been used in psoriasis patients, reports of major cardiovascular events (MACEs) have emerged. This study aims to investigate the association between MACEs and biologic psoriasis therapies by using information reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: FAERS data (January 2004 to December 2022) were reviewed. For each drug-event pair, the proportional reporting ratio (PRR) and the multi-item gamma Poisson shrinker (MGPS) algorithms were used to identify drug-adverse event associations. Results: We filtered the query for indication and identified 173,330 reports with psoriasis indication in FAERS throughout the analyzed time frame. MACEs occurred in 4,206 patients treated with biologics. All the four biological classes had an elevated and similar reporting rates for MACEs relative to other alternative psoriasis treatments (PRR from 2.10 to 4.26; EB05 from 1.15 to 2.45). The descending order of association was IL-12/23 inhibitors>IL-17 inhibitors>IL-23 inhibitors>TNF inhibitors. The signal strength for myocardial infarction (PRR, 2.86; χ2, 296.27; EBGM 05, 1.13) was stronger than that for stroke, cardiac fatality, and death. All the biological classes demonstrated a little higher EBGM 05 score≥1 for the MACEs in patients aged 45-64 years. The time-to-onset of MACEs was calculated with a median of 228 days. Conclusions: Analysis of adverse event reports in the FAERS reflects the potential risk of MACEs associated with the real-world use of biological therapies in comparison to other alternative psoriasis treatments. Future long-term and well-designed studies are needed to further our knowledge regarding the cardiovascular safety profile of these agents.

Postmarket safety profile of suicide/self-injury for GLP-1 receptor agonist: a real-world pharmacovigilance analysis.

BACKGROUND: Recent reports of individuals experiencing suicidal and/or self-injurious behaviors while using liraglutide and semaglutide have heightened the concerns regarding neuropsychiatric safety of Glucagon-like peptide-1 agonists (GLP-1RAs). As real-world evidence is very limited, we explored the association between GLP-1RA and suicide/self-injury by mining the FDA Adverse Event Reporting System (FAERS) database. METHODS: The FAERS database was queried from 2005 Q2 to 2023 Q2. The Reporting Odds Ratio (ROR) and Empirical Bayes Geometric Mean (EBGM) were used to conduct the disproportionality analysis. RESULTS: A total of 534 GLP-1RA-associated suicide/self-injury cases were reported in the FAERS during the study period. GLP-1RA did not cause a disproportionate increase in overall suicidal and self-injurious cases (ROR: 0.16, 95%CI 0.15-0.18, P < 0.001; EBGM05: 0.15). Stratified analyses found no safety signal of suicide/injury for GLP-1RA in both females and males. The ROR for suicide/self-injury with GLP-1RA was slightly elevated (ROR: 2.50, 95%CI 1.02-6.13, P = 0.05) in children, while the EBGM05 was < 2 in this population. No significant signal value was observed in other age groups. No over-reporting of suicide/self-injury was identified for GLP-1RA before or after the COVID-19 pandemic outbreak. CONCLUSIONS: The cases of suicide or self-injury reported to FAERS do not indicate any overall safety signal attributable to GLP-1RA at this time. Subgroup analysis revealed a marginal elevation of ROR for suicide and self-injury with GLP-1RA in children, but no safety signal was detected by EBGM05 in this population. Further large-scale prospective investigations are still warranted to further confirm this finding.

Real-world evidence of autoimmune hepatitis following COVID-19 vaccination: A population-based pharmacovigilance analysis.

Objective: Autoimmune hepatitis (AIH) has occasionally been reported after administration of Coronavirus Disease 2019 (COVID-19) vaccine. The present study aimed to investigate the reported rate and disproportionality of AIH following COVID-19 vaccination. Methods: The Centers for Disease Control (CDC) COVID Data Tracker and the Vaccines Adverse Event Reporting System (VAERS) were queried between 11 December 2020 and 15 March 2022. Reported rates were calculated by cases of AIH divided by the number of vaccinated people. Disproportionate pattern of AIH for COVID-19 vaccination was accessed based on the reporting odds ratio and empirical bayes geometric mean (ROR and EBGM, respectively). Results: A total of 53 reports of AIH were identified after administration of COVID-19 vaccine during the study period. The overall reported rate of COVID-19 vaccination-related AIH was 0.21 (95% CI 0.16-0.27) per million people. The results found no disproportionate reporting of AIH following COVID-19 vaccination in the VAERS (overall: ROR 1.43, 95% CI 0.52-3.96; EBGM05 0.37. mRNA: ROR 1.42, 95% CI 0.51-3.94; EBGM05 0.37. Virus vector: ROR 1.57, 95% CI 0.42-5.85; EBGM05 0.34). Conclusion: COVID-19 vaccine did not increase the risk of AIH. The number of AIH cases reported to VAERS does not suggest a safety concern attributable to COVID-19 vaccine at this time.

Updated insights on dementia-related risk of sacubitril/valsartan: A real-world pharmacovigilance analysis.

AIM: Sacubitril/valsartan is a new cardiovascular agent characterized by its dual inhibition on the reninangiotensin system (RAS) and the neprilysin. As neprilysin also involved itself in the degradation of amyloid-ß, there is an ongoing concern about the effect of sacubitril/valsartan on cognition, especially in case of long-term administration. METHODS: The FDA Adverse Event Reporting System (FAERS) was mined between 2015Q3 and 2022Q4 to analyze the association between sacubitril/valsartan and adverse events (AEs) involving dementia. Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) with "broad" and "narrow" preferred terms (PTs) relevant to dementia was applied to systematically search demented AE reports. The Empirical Bayes Geometric Mean (EBGM) from Multi-Item Gamma Poisson Shrinker (MGPS) and proportional reporting ratio with Chi-square (PRR, χ2 ) were used to calculate the disproportionality. RESULTS: We filtered the query for indication and identified 80,316 reports with heart failure indication in FAERS during the analytical period. Among all the reports, sacubitril/valsartan was listed as primary suspected or secondary suspected drug in 29,269 cases. No significantly elevated reporting rates of narrow dementia were evident with sacubitril/valsartan. The EBGM05 for narrow dementia-related AEs associated with sacubitril/valsartan was 0.88 and the PRR (χ2 ) was 1.22 (2.40). Similarly, broad demented complications were not over-reported in the heart failure patients administrated with sacubitril/valsartan (EBGM05 1.11; PRR 1.31, χ2 109.36). CONCLUSION: The number of dementia-related cases reported to FAERS generate no safety signal attributable to sacubitril/valsartan in patients with heart failure for now. Further follow-ups are still warranted to address this question.

Booster dose of COVID-19 mRNA vaccine does not increase risks of myocarditis and pericarditis compared with primary vaccination: New insights from the vaccine adverse event reporting system.

Background: Despite the likely association between coronavirus 2019 (COVID-19) mRNA vaccines and cases of myocarditis/pericarditis, the benefit-risk assessment by the Centers for Disease Control (CDC) still showed a favorable balance for the primary series of COVID-19 mRNA vaccinations. Since August 2021, a full-scale booster vaccination in certain recipients has been recommended. Great concerns about whether the COVID-19 mRNA booster vaccination could increase the risks of myocarditis/pericarditis have been raised since then. The present study aimed to compare the incidence rates and risks of myocarditis/pericarditis between booster and primary vaccination programs. Methods: The CDC COVID Data Tracker and the Vaccines Adverse Event Reporting System (VAERS) were queried between December 11, 2020 and March 15, 2022. Incidence rates were calculated by cases of myocarditis/pericarditis divided by the number of vaccinated people or the total doses of COVID-19 mRNA vaccines. Disproportionality patterns for myocarditis/pericarditis of different COVID-19 mRNA vaccinations were accessed based on the reporting odds and proportional reporting ratios (ROR and PRR, respectively). Results: A total of 2,588 reports of myocarditis/pericarditis were identified after administration of primary-series COVID-19 mRNA vaccination and 269 after the booster dose program during the study period. The incidence of myocarditis/pericarditis following booster COVID-19 mRNA vaccination was lower than that of primary series. The results showed significantly high reporting of myocarditis/pericarditis following the administration of primary COVID-19 mRNA vaccination, whereas the disproportional level was lower in the booster-dose vaccination. Conclusion: This study found that the booster dose of COVID-19 mRNA vaccination when compared with primary series course did not lead to an increase in the risks of myocarditis/pericarditis.

Hearing disorder following COVID-19 vaccination: A pharmacovigilance analysis using the Vaccine Adverse Event Reporting System.

WHAT IS KNOWN AND OBJECTIVE: Evidence on whether the coronavirus disease 2019 (COVID-19) vaccination could cause hearing-related adverse events is still conflicting. This study aims to access the association between COVID-19 vaccine and hearing disorder. METHODS: The Vaccine Adverse Event Reporting System (VAERS) was queried between January 2020 to November 2021. The disproportionality pattern for hearing impairment of COVID-19 vaccine was accessed by calculating the reporting odds ratio (ROR) and proportional reporting ratio (PRR). A further subgroup analysis based on the type of COVID-19 vaccine and the doses administered was performed. In addition, the disproportionalities for hearing dysfunction between COVID-19 and influenza vaccines were compared. RESULTS AND DISCUSSION: A total of 14,956 reports of hearing-related adverse events were identified with COVID-19 vaccination and 151 with influenza vaccine during the analytic period in VAERS. The incidence of hearing disorder following COVID-19 vaccination was 6.66 per 100,000. The results of disproportionality analysis revealed that the adverse events of hearing impairment, after administration of COVID-19 vaccine, was significantly highly reported (ROR 2.38, 95% confidence interval [CI] 2.20-2.56; PRR: 2.35, χ2 537.58), for both mRNA (ROR 2.37, 95% CI 2.20-2.55; PRR 2.34, χ2 529.75) and virus vector vaccines (ROR 2.50, 95% CI 2.28-2.73; PRR 2.56, χ2 418.57). While the disproportional level for hearing dysfunction was quite lower in influenza vaccine (ROR 0.36, 95% CI 0.30-0.42; PRR 0.36, χ2 172.24). WHAT IS NEW AND CONCLUSION: This study identified increased risk for hearing disorder following administration of both mRNA and virus vector COVID-19 vaccines compared to influenza vaccination in real-world settings.

Musculoskeletal Adverse Events Associated with PCSK9 Inhibitors: Disproportionality Analysis of the FDA Adverse Event Reporting System.

BACKGROUND: Some studies suggest that potential safety issues about PCSK9 inhibitors have not been sufficiently explored in clinical trials, including musculoskeletal adverse events (MAEs). OBJECTIVE: To examine the association between use of PCSK9 inhibitors with and without concurrent statins and risk of MAEs. Patients and Methods. FDA Adverse Event Reporting System (FAERS) dataset of PCSK9 inhibitors and statins from October 2015 to June 2021 was queried. The reporting odds ratio (ROR) with relevant 95% confidence interval (95% CI) was calculated as the index of disproportionality. Outcome of MAEs of different PCSK9 inhibitors regimens was also investigated. RESULTS: 3,185 cases of PCSK9 inhibitor-associated MAEs were recorded. PCSK9 inhibitor class alone demonstrated a strong link to MAEs (ROR 5.92; 95% CI 5.70-6.15), and evolocumab was associated with more reports of MAEs than alirocumab. Concomitant use with statins leaded to an increased occurrence of MAEs (ROR 32.15 (25.55-40.46)), and the risk differed among different statins. The PCSK9 inhibitors were safer than statins in terms of hospitalization rate and death rate (15.64% vs. 36.83%; 0.72% vs. 3.53%). CONCLUSIONS: This pharmacovigilance investigation suggests that PCSK9 inhibitors are associated with MAEs. The risk significantly increases when combined with statins. Increased laboratory and clinical monitoring are required to timely diagnose and manage MAEs.

Does the conventional dosage of linezolid necessitate therapeutic drug monitoring?-Experience from a prospective observational study.

BACKGROUND: The objectives of the present prospective observational study conducted in patients receiving conventional dosage of linezolid was to define the pharmacodynamic range of linezolid exposure, to assess the inter-individual variability in linezolid concentrations, and to define if therapeutic drug monitoring (TDM) of linezolid may be necessary for Chinese population. METHODS: Patients included in this study underwent linezolid TDM trough concentration (C min) during treatment with a standard regimen in the period between January 2019 and October 2019. Linezolid C min was analyzed with high-performance liquid chromatography (HPLC) method. Logistic regression was used to define the desired range of linezolid C min. Linear regression and univariate logistic regression analysis were carried out to investigate variables associated with inappropriate linezolid plasma exposure. RESULTS: A total of 84 patients who had 153 linezolid C min assessed were included in the study. Median linezolid C min was 3.43 mg/L (IQR 1.59-5.93). The estimated probability of thrombocytopenia was 50% in the presence of C min of 7.85 mg/L. Approximately 57.52% (88/153) of the samples fell within the desired range of linezolid C min (2-8 mg/L) while 31.37% (48/153) experienced underexposure, and overexposure occurred in 11.11% (17/153) of the patients. No significant linear relationships between either body weight or estimated creatinine clearance (CrCL) and C min were detected. Estimated CrCL ≥100 mL/min was significantly associated with linezolid underexposure (OR 4.121; 95% CI, 1.945-8.731; P<0.001). Estimated CrCL ≤40 mL/min was significantly associated with linezolid overexposure (OR 3.761; 95% CI, 1.324-10.681; P=0.013). CONCLUSIONS: Our results suggest that the pharmacodynamic range of linezolid C min can be defined as 2-8 mg/L for the Chinese population. Renal function partially accounts for the inter-interindividual variability of exposure. The application of TDM might be especially valuable in optimizing linezolid exposure in the majority of patients to avoid therapeutic failure and/or dose-dependent adverse reactions.

Subtherapeutic Linezolid Concentration in a Patient With Bullous Pemphigoid Complicated by Methicillin-Resistant Staphylococcus aureus Infection: A Case Study.

We presented a case of subtherapeutic linezolid concentration in a patient with bullous pemphigoid characterized by large area skin anabrosis complicated by methicillin-resistant Staphylococcus aureus infections.

A novel inhibitor of ADAM17 sensitizes colorectal cancer cells to 5-Fluorouracil by reversing Notch and epithelial-mesenchymal transition in vitro and in vivo.

OBJECTIVES: Colorectal cancer is one of the most common malignancies both in men and women. Owing to metastasis and resistance, the prognosis of colorectal cancerCRC patients remains extremely poor with chemotherapy. A disintegrin and metalloproteinase 17 (ADAM17) induces the activation of Notch pathway and contributes to the chemoresistance. This study aimed to discover a novel ADAM17 inhibitor and investigate the chemosensitization effect. MATERIALS AND METHODS: Pharmacophore model, western blot and enzymatic assay were used to discover ZLDI-8. Cell proliferation was determined by MTT and colony formation assay. Cell migratory and invasive ability were determined by wound healing scratch and transwell assay. Immunofluorescence images and western blot analysed the expression of Notch or epithelial-mesenchymal transition (EMT) pathway markers. Xenografts were employed to evaluate the chemosensitization effect of ZLDI-8 in vivo. RESULTS: We found that ZLDI-8 cell-specifically inhibited the proliferation of CRC, and this effect was due to abrogation of ADAM17 and Notch pathway. Meanwhile, we reported for the first time that ZLDI-8 synergistically improved the anti-tumour and anti-metastasis activity of 5-fluorouracil or irinotecan by reversing Notch and EMT pathways. Interestingly, in vivo studies further demonstrated that ZLDI-8 promoted the anti-tumour effect of 5-fluorouracil through Notch and EMT reversal. CONCLUSIONS: A novel ADAM17 inhibitor ZLDI-8 may be a potential chemosensitizer which sensitized CRC cells to 5-fluorouracil or irinotecan by reversing Notch and EMT pathways.

Anti-proliferative and pro-apoptotic activities of Alpinia oxyphylla on HepG2 cells through ROS-mediated signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Alpiniae oxyphyllae (A. oxyphylla) is a traditional herb which is widely used in East Asian for the treatment of dyspepsia, diarrhea, abdominal pain, poor memory, inflammatory conditions and cancer. MATERIALS AND METHODS: The cytotoxic activities of ethanol extract (EE) and five extract layers including petroleum ether (PE), dichloromethane (DCLM), acetoacetate (EtOAc), n-Butanol (n-Bu) and water fractions (WF) of A. oxyphylla were tested on HepG2, SW480, MCF-7, K562 and HUVEC cell lines using MTT assay and LDH release assay. The component analysis was performed on HPLC with gradient elution. Hoechst 33342 staining, DCFH-DA fluorescence microscopy, flow cytometry analysis, western blot and migration assays were carried out to determine the anti-cancer mechanisms of PE. RESULTS: MTT analysis showed that EE, PE and DCLM could inhibit cell proliferation on HepG2, SW480, MCF-7, K562 and HUVEC cell lines, especially PE fraction. HPLC analysis pointed out five main components which may contribute to the anti-proliferative activity of PE. Further study showed that PE increased LDH release, induced apoptosis, disrupted mitochondrial membrane potential and elevated intracellular reactive oxygen species (ROS) in HepG2 cells, whereas the antioxidant N-acetyl-l-cysteine (NAC) prevented PE-induced ROS generation. The results of western blot revealed that PE induced apoptosis in HepG2 cells by enhancing Bax/Bcl-2 ratio, increasing cytochrome c in cytosol and activating caspase-3/9. Meanwhile, high levels of ROS could induce DNA damage-mediated protein expression, AKT, ERK inactivation and SAPKs activation. Furthermore, PE conspicuously blocked the migration of HUVEC cells. CONCLUSION: The present results demonstrated that PE induced apoptosis in HepG2 cells may be via a ROS-mediated signaling pathway.

Phosphorylation of ribosomal protein S6 kinase 1 at Thr421/Ser424 and dephosphorylation at Thr389 regulates SP600125-induced polyploidization of megakaryocytic cell lines.

Megakaryocytes (MKs) are one of the few cell types that become polyploid; however, the mechanisms by which these cells are designated to become polyploid are not fully understood. In this investigation, we successfully established two relatively synchronous polyploid cell models by inducing Dami and CMK cells with SP600125. We found that SP600125 induced the polyploidization of Dami and CMK cells, concomitant with the phosphorylation of ribosomal protein S6 kinase 1 (S6K1) at Thr421/Ser424 and dephosphorylation at Thr389. The polyploidization was partially blocked by H-89, a cAMP-dependent protein kinase (PKA) inhibitor, through direct binding to S6K1, leading to dephosphorylation at Thr421/Ser424 and phosphorylation at Thr389, independent of PKA. Overexpression of a rapamycin-resistant mutant of S6K1 further enhanced the inhibitory effect of LY294002 on the SP600125-induced polyploidization of Dami and CMK cells. SP600125 also induced the polyploidization of Meg-01 cells, which are derived from a patient with chronic myelogenous leukemia, without causing a significant change in S6K1 phosphorylation. Additionally, SP600125 induced the polyploidization of HEL cells, which are derived from a patient with erythroleukemia, and phosphorylation at Thr389 of S6K1 was detected. However, the polyploidization of both Meg-01 cells and HEL cells as a result of SP600125 treatment was lower than that of SP600125-induced Dami and CMK cells, and it was not blocked by H-89 despite the increased phosphorylation of S6K1 at Thr389 in both cell lines in response to H-89. Given that the Dami and CMK cell lines were derived from patients with acute megakaryocytic leukemia (AMKL) and expressed high levels of platelet-specific antigens, our data suggested that SP600125-induced polyploidization is cell-type specific, that these cell lines were more differentiated, and that phosphorylation at Thr421/Ser424 and dephosphorylation at Thr389 of S6K1 may play an important role in the SP600125-induced polyploidization of these cell lines synergistically with other signaling pathways.

Isoindolone derivative QSN-10c induces leukemic cell apoptosis and suppresses angiogenesis via PI3K/AKT signaling pathway inhibition.

AIM: 2-(4,6-Dimethoxy-1,3-dioxoisoindolin-2-yl) ethyl 2-chloroacetate (QSN-10c) is one of isoindolone derivatives with antiproliferative activity against human umbilical vein endothelial cells (HUVECs). The aim of this study was to investigate its antitumor activity in vitro and anti-angiogenic effects in vitro and in vivo. METHODS: K562 leukemic cells and HUVECs were used for in vitro studies. Cell viability was examined using MTT assay. Cell apoptosis and mitochondrial transmembrane potential (Δψm) were detected with flow cytometry. Tube formation and migration of HUVECs were studied using two-dimensional Matrigel assay and wound-healing migration assay, respectively. VEGF levels were analyzed with RT-PCR and Western blotting. A zebrafish embryo model was used for in vivo anti-angiogenic studies. The molecular mechanisms for apoptosis in K562 cells and antiangiogenesis were measured with Western blotting. RESULTS: In antitumor activity studies, QSN-10c suppressed the viability of K562 cells and induced apoptosis in dose- and time-dependent manners. Furthermore, QSN-10c dose-dependently decreased the Δψm in K562 cells, increased the release of cytochrome c and the level of Bax, and decreased the level of Bcl-2, suggesting that QSN-10c-induced apoptosis of K562 cells was mediated via the mitochondrial apoptotic pathway. In anti-angiogenic activity studies, QSN-10c suppressed the viability of HUVECs and induced apoptosis in dose dependent manners. QSN-10c treatment did not alter the Δψm in HUVECs, but dose-dependently inhibited the expression of VEGF, inhibited the tube formation and cell migration in vitro, and significantly suppressed the number of ISVs in zebrafish embryos in vivo. Furthermore, QSN-10c dose-dependently suppressed the phosphorylation of AKT and GSK3ß in both HUVECs and K562 cells. CONCLUSION: QSN-10c is a novel antitumor compound that exerts both antitumor and anti-angiogenic effects via inhibiting the PI3K/AKT/GSK3ß signaling pathway.

WLIP derived from Lasiosphaera fenzlii Reich exhibits anti-tumor activity and induces cell cycle arrest through PPAR-γ associated pathways.

White-line-inducing principle (WLIP), a lipodepsipeptide isolated from Lasiosphaera fenzlii Reich., which is one of the puffballs, for the first time, has been reported to exhibit anti-microbial activity. However, there are no reports regarding the anti-tumor effects of WLIP. In this study, we reported the anti-cancer effects of WLIP on K562 cells, and its potential effect on the PPAR-γ activation pathway. The obtained results showed that WLIP exerted strong anti-proliferative effect on K562 cells. Moreover, WLIP was found to increase apoptosis and induce G0/Gl arrest. Modeling results from the Surflex-Dock program suggested that PPAR-γ might be the potential anti-tumor target of WLIP, which was confirmed by the experiments that WLIP increased the activity in luciferase reporter assay and the expression of PPAR-γ in Western blot. Besides, WLIP was able to down-regulate the expression of Bcl-xL, Cyclin-D1 in K562 cells. In summary, our novel observations suggested that WLIP might have a potential implication in cancer prevention and treatment, and also showed for the first time that the anti-tumor effect of WLIP might be mediated through modulation of the PPAR-γ activation pathway.