Although glutamine-rich protein 1 (QRICH1) has been implicated in endoplasmic reticulum stress-associated epithelial-mesenchymal transition (EMT), its mechanistic role in liver cancer progression remains unclear. QRICH1 expression was analyzed in public datasets and clinical liver cancer specimens. Gain- and loss-of-function approaches were performed to assess proliferation, migration, invasion, and EMT signaling in vitro, and tumorigenicity was evaluated using a xenograft mouse model. QRICH1 was significantly overexpressed in liver cancer tissues with poor clinical outcomes. QRICH1 silencing markedly suppressed cell proliferation, migration, invasion, and EMT, accompanied by decreased Snail1 and ZEB1 expression and restoration of Connexin43 (GJB1). Co-immunoprecipitation and immunofluorescence analyses demonstrated that QRICH1 physically interacted and colocalized with Snail1 and USP1. Molecular docking further supported stable binding interfaces among these proteins. Ubiquitination and cycloheximide chase assays revealed that QRICH1 enhanced Snail1 protein stability through USP1-mediated deubiquitination. Functionally, QRICH1 suppressed gap junction intercellular communication, consistent with reduced Connexin43 expression, but not Connexin26 and Connexin32. In vivo, QRICH1 knockdown significantly inhibited tumor growth and reduced the expression of USP1, Snail1, PCNA, VEGF, and N-cadherin, while increasing E-cadherin and Connexin43. Collectively, these findings identify QRICH1 as a key oncogenic regulator that promotes liver cancer progression by stabilizing Snail1 via USP1-dependent deubiquitination and disrupting Connexin43-mediated gap junction signaling

Although benzyl isothiocyanate (BITC), a major compound found in cruciferous vegetables, has been reported to exert antitumor effects in various cancers, its apoptotic mechanism remains unclear. This study aimed to elucidate the apoptotic mechanism of BITC by investigating its role in inhibiting Warburg effect in hepatocellular carcinoma (HCC) cells. BITC suppressed cell proliferation, increased the sub-G1 population, Annexin V/PI and reduced the expression of pro-poly (ADP-ribose) polymerase (pro-PARP), pro-caspase-3, CCR4-NOT transcription complex subunit 2 (CNOT2), c-Myc, signal transducer and activator of transcription 3 (STAT3), and phosphorylated Janus kinase 1 (p-JAK1) in SK-Hep1 and Huh7 HCC cell lines. Notably, knockdown of STAT3 or its upstream regulator CNOT2 further enhanced BITC-induced apoptosis, as evidenced by decreased pro-PARP and pro-caspase-3 expression in SK-Hep1 cells. Additionally, BITC attenuated the expression of hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), and lactate dehydrogenase (LDH) along with reduced LDH production and glucose in SK-Hep1 and Huh7 cells. However, treatment of pyruvate or overexpression of CNOT2 or c-Myc reversed the capacity of BITC to reduce the expression of HK2, pro-caspase-3, and pro-PARP in SK-Hep1 cells. Immunoprecipitation assays further revealed that BITC disrupted the interactions between CNOT2 and STAT3 or c-Myc. Collectively, these findings suggest that the CNOT2/c-Myc/STAT3 signaling axis plays a critical role in glycolysis mediated apoptosis of BITC in HCC cells.

The hormone melatonin, secreted by the pineal gland, has attracted considerable interest due to its potential to prevent liver disorders by its strong antioxidant characteristics. This review examines the diverse functions of melatonin in maintaining liver health, with a specific emphasis on its mechanisms of action in different liver diseases. Melatonin counteracts the harmful effects of alcohol on the liver by reducing oxidative stress and maintaining the proper functioning of mitochondria. Melatonin improves insulin sensitivity and regulates lipid metabolism in metabolic liver diseases, such as non-alcoholic fatty liver disease (NAFLD), and decreasing hepatic steatosis. The anti-inflammatory properties of this substance are obtained by reducing pro-inflammatory cytokines signaling pathways, which protect against diseases such as hepatitis and steatohepatitis. In addition, melatonin demonstrates anti-fibrotic characteristics by inhibiting the activation of hepatic stellate cells and decreasing the production of fibrogenic cytokines, reducing the severity of liver fibrosis. Within the realm of hepatocellular carcinoma (HCC), melatonin triggers programmed cell death that hinders the growth of cells and represses the formation of new blood vessels, augmenting the effectiveness of traditional treatments. Research has shown that melatonin is safe and effective in treating liver problems. However, further large-scale, multicenter randomized clinical trials are required to establish the optimal therapeutic dose, treatment duration, long-term safety, and clinical efficacy of melatonin in patients with liver diseases. Future research should focus on clarifying the specific molecular targets of melatonin, enhancing its bioavailability, and creating combination therapies. The existing evidence indicates that melatonin is a potentially beneficial supplementary treatment and preventive medication for liver disorders, owing to its antioxidant, anti-inflammatory, anti-fibrotic, and metabolic regulating characteristics. Nonetheless, additional well designed clinical trials are necessary to determine its ideal therapeutic use and promote its integration into clinical practice.

Though Rhus verniciflua and Artemisia capillaris have been traditionally prescribed for liver ailments, the molecular antitumor mechanism of their ethanol extract (RHART) remains undefined in hepatocellular carcinoma (HCC). Thus, this study aimed to elucidate the apoptotic mechanisms of RHART, focusing on its regulation of oncogenic drivers-cleavage and polyadenylation specificity factor 6 (CPSF6), monocarboxylate transporter 4 (MCT4), and c-Myc-and glycolysis-related pathways. RHART quality was standardized by HPLC fingerprinting. Cytotoxicity, apoptosis, and protein expression were analyzed using MTT, cell cycle, and Western blot assays in RHART-treated Hep3B and Huh7 cells. Functional rescue assays were conducted by overexpressing CPSF6 or c-Myc, while CPSF6-MCT4 interaction was confirmed by immunoprecipitation. The in vivo efficacy of RHART was validated using Hep3B xenografts in BALB/c nude mice followed by immunohistochemistry. RHART treatment induced pronounced cytotoxicity and apoptosis, as indicated by an elevated sub-G1 population and cleavage of PARP and caspase-3. RHART markedly downregulated CPSF6, MCT4, c-Myc, and glycolytic enzymes (HK2, PKM2, LDHA), thereby reducing glucose utilization and lactate output. CPSF6 directly interacted with MCT4, and overexpression of CPSF6 or c-Myc counteracted the capacity of RHART to induce apoptosis and metabolic reprogramming. In vivo, RHART significantly suppressed tumor growth and expression of CPSF6, MCT4, PCNA, and PKM2, while enhancing cleaved caspase-3. These findings provide scientific evidence that RHART induces apoptotic and metabolic reprogramming effects in hepatocellular carcinoma by targeting the CPSF6/MCT4/c-Myc signaling axis, underscoring its potential as a novel natural therapeutic candidate for liver cancer.

Cornin, a bioactive iridoid glycoside isolated from Cornus officinalis, has been reported to exhibit cardioprotective and pro-apoptotic activities. However, its antitumor mechanism in cervical cancer remains largely unknown. In this study, we investigated the antiangiogenic and anti-invasive effects of Cornin, focusing on the CNOT2-VEGF signaling axis. Cornin showed limited cytotoxicity in SiHa, HeLa, and CaSki cervical cancer cells but significantly downregulated CNOT2, N-cadherin, VEGF, and Snail expression in HeLa and SiHa cells. Functional analyses revealed that CNOT2 silencing suppressed wound healing activity, while Cornin treatment markedly inhibited cell migration, invasion, and VEGF secretion in HeLa cells. VEGF luciferase reporter and cycloheximide chase assays confirmed that Cornin reduced VEGF transcription and protein stability in a time-dependent manner. Furthermore, Cornin inhibited tube formation in HUVECs and angiogenesis in the chick chorioallantoic membrane (CAM) model. TCGA analysis showed that CNOT2 expression was elevated in cervical cancer tissues and positively correlated with VEGF expression (r = 0.35). This association was further supported by immunoprecipitation analysis demonstrating a physical interaction between CNOT2 and VEGF in HeLa cells. Mechanistically, ectopic CNOT2 expression upregulated VEGF, whereas its depletion suppressed VEGF expression. Collectively, these findings highlight the CNOT2-VEGF axis as a crucial mediator in antiangiogenic and anti-invasive effects of Cornin in cervical cancer, suggesting Cornin as a potent natural inhibitor of tumor angiogenesis and invasion.

Nucleolar protein 56 (NOP56), a core component of small nucleolar ribonucleoprotein complexes, has been implicated in oncogenesis through the regulation of reactive oxygen species (ROS) homeostasis; however, its role in colorectal cancer (CRC) remains unclear. Here, we investigated the clinical relevance and biological function of NOP56 in CRC using TCGA datasets, tissue microarrays, next-generation sequencing, and in vitro and in vivo models. NOP56 expression was markedly elevated in CRC tissues compared with adjacent normal tissues and was correlated with poor patient survival. Silencing of NOP56 suppressed cell viability, colony formation, and migration, particularly in p53 wild-type HCT116 cells, and altered gene expression programs related to DNA damage response and apoptosis. Mechanistically, NOP56 depletion induced cell cycle arrest and apoptosis, accompanied by increased p53 and p21 levels and reduced expression of pro-caspase-3, c-Myc, Cyclin E, CDK2, CDK4, MDM2, and SIRT1. Conversely, NOP56 overexpression promoted p53 degradation, whereas its knockdown enhanced p53 stability and acetylation through suppression of SIRT1 and activation of p300, as supported by evidence of direct interaction and colocalization. Furthermore, NOP56 silencing synergistically enhanced the cytotoxic effect of 5-fluorouracil (5-FU). In a xenograft model, NOP56 knockdown markedly reduced tumor growth as well as PCNA and SIRT1 expression, while increasing p53 and cleaved caspase-3 levels. Collectively, these findings identify NOP56 as an oncogenic driver that promotes CRC progression by inducing p53 degradation, whereas its inhibition triggers apoptosis via p53 acetylation regulated by the SIRT1/p300 axis, highlighting NOP56 as a promising therapeutic target for p53 wild-type CRC.

Background/Objectives: Hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) has been reported to improve survival in patients with peritoneal carcinomatosis. This study aimed to investigate the morbidity and mortality rates of CRS with HIPEC in patients with ovarian cancers. Methods: We retrospectively reviewed the medical records of patients who underwent CRS with HIPEC for ovarian cancer from January 2013 to July 2021 at two tertiary institutions. The morbidities and mortalities that occurred within 30 days after HIPEC and the clinical and operative factors related to morbidities were investigated. Results: A total of 155 procedures in 151 patients were included in this study. The median age was 55 years and the median score of the peritoneal carcinomatosis index was eight points. Morbidities of grade ≥3 within 30 days of HIPEC occurred in 18 patients (11.6%). The most common severe morbidity was wound infection (3.2%), followed by pleural effusion (1.9%) and postoperative hemorrhage (1.9%). Within the 30-day postoperative period, there were no reported mortality cases. There were statistical differences in age, length of stay, peritoneal carcinomatosis index, bowel resection, operation time, and completeness of cytoreduction between the patients and severe morbidity. However, in the multivariate logistic analysis, none of the factors showed a statistically significant relationship with the occurrence of severe morbidity. Conclusions: The morbidity and mortality rates of CRS with HIPEC in gynecologic cancer patients were relatively low compared to those in previous reports. Further studies about the possible risk factors are needed.

Supplementary MethodsSupplementary Figure 1-5Supplementary Table 1-2

With the ever-increasing demand for AI and data-intensive applications, $3\mathrm{D}$ NAND Flash memories [1]–[6] need to achieve both high-density and high-speed IOS. Higher density can be attained by removing dummy holes in the cell array and increasing the number of stacked WLs. However, removal of dummy holes renders the GSL-cut process inapplicable [3]; thus, increasing power consumption due to the capacitance of unselected strings. Moreover, as the number of WLs increases, the amount of pass-voltage disturbance, which is directly related to the number of unselected WL, thereby deteriorating cell reliability. In addition, increased WL capacitance result in degradation of the program $(\mathrm{t}_{\text{PROG}})$ and read $(\mathrm{t}_{\mathrm{R}})$ time. Achieving high-speed $\text{IOS}$ also poses signal-integrity (SI) challenges: stringent eye-width (EW) and eye-height (EH) requirements; while also maintaining high 10 bandwidth and low-power consumption.

Lysyl-tRNA synthetase 1 (KARS1), an aminoacyl-tRNA synthetase, was recently identified as a secreted pro-inflammatory agent. However, the vascular secretion and functions of KARS1 have not been characterized. This study investigated the secretion mechanisms of KARS1 and explored its functional roles in vascular biology. We found that KARS1 expression was upregulated by oscillatory shear stress, an atherogenic factor, suggesting the presence of free KARS1 dissociated from aminoacyl-tRNA synthetase complexes. Moreover, in the presence of Ca2+, serum starvation triggered free cytosolic KARS1 release from endothelial cells via secretory autophagy. Both phosphatidylinositol 3-phosphate kinase and caveolin-1 were either supplementary or essential for KARS1 secretion. Secreted KARS1 co-localized in the exosome fraction of post-culture media and was externally exposed. Further, secreted KARS1 inhibited shear-induced activation of various signaling molecules, including extracellular signal-regulated kinase, protein kinase B, and endothelial nitric oxide synthetase. Secreted KARS1 in atherosclerotic plaques also acted as an atherogenic or proinflammatory autocrine/paracrine molecule. Additionally, KARS1 participated in vessel alteration. Collectively, these findings describe novel vascular features of KARS1 in response to shear stress, providing insights into shear stress-controlling mechanisms of the vascular system.

Background:Though ZBTB7B is overexpressed in breast and prostate cancers and dysregulates CD8 T cell response, there is no report on the close relationship between ZBTB7B and androgen receptor (AR) yet. This study aimed to investigate the molecular interaction between ZBTB7B and AR and to determine its role in prostate cancer progression. Methods:Prostate cancer cell lines (AR-dependent LNCaP and AR-independent DU145) were subjected to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, clonogenic assay, and cell cycle analysis. Protein-protein interaction was examined using immunoprecipitation and immunofluorescence. Protein stability was assessed by cycloheximide chase and ubiquitination assays. RNA interference was employed to deplete ZBTB7B or AR, and tissue expression patterns were analyzed by The Cancer Genome Atlas (TCGA) and human tissue microarray. Results:ZBTB7B was overexpressed in prostate cancer cells and tissues with poor prognosis by human tissue microarray and TCGA analysis. However, ZBTB7B depletion suppressed viability, the number of colonies and increased G1 arrest in AR dependent LNCaP cells, but not in AR independent DU145 cells. Interestingly, ZBTB7B depletion suppressed the expression of AR and prostate specific antigen (PSA) in LNCaP cells, while AR depletion did not affect ZBTB7B. Furthermore, AR inhibitor finasteride and AR activator dihydrotestosterone (DHT) did not affect ZBTB7B. However, ZBTB7B was colocalized with AR by immunofluorescence and was bound to AR by immunoprecipitation. Consistently, ZBTB7B depletion attenuated the nuclear translocation and stability of AR through its degradation and also promoted AR degradation by ubiquitination assay. Notably, N-terminal domain (NTD) of AR is requisite for binding with ZBTB7B in HEK293 cells, not AR-DNA-binding domain (DBD) or AR-ligand-binding domain (LBD) in HEK293 cells. Conclusions:Overall, these findings provide a novel insight that ZBTB7B promotes prostate cancer progression as a potent oncogene via colocalization and binding with AR.

Cancer-associated myeloid cells due to their plasticity play dual roles in both promoting and inhibiting tumor progression. Myeloid cells with immunosuppressive properties play a critical role in anti-cancer immune regulation. Cells of different origin, such as tumor associated macrophages (TAMs), tumor associated neutrophils (TANs), myeloid derived suppressor cells (also called MDSCs) and eosinophils are often expanded in cancer patients and significantly influence their survival, but also the outcome of anti-cancer therapies. For this reason, the variety of preclinical and clinical studies to modulate the activity of these cells have been conducted, however without successful outcome to date. In this review, pro-tumor activity of myeloid cells, myeloid cell-specific therapeutic targets, in vivo studies on myeloid cell re-polarization and the impact of myeloid cells on immunotherapies/genetic engineering are addressed. This paper also summarizes ongoing clinical trials and the concept of chimeric antigen receptor macrophage (CAR-M) therapies, and suggests future research perspectives, offering new opportunities in the development of novel clinical treatment strategies.

PURPOSE:Considering the current lack of consensus on post-poly(adenosine diphosphate-ribose) polymerase inhibitor (PARPi) treatment strategies, this study aimed to evaluate the efficacy of subsequent therapy and compare the outcomes of regimes in patients with recurrent ovarian cancer after PARPi treatment. MATERIALS AND METHODS:This multi-center retrospective cohort study analyzed data on patients diagnosed with ovarian cancer between January 2012 and June 2023 who had previously used PARPi after first- to fourth-line platinum-based chemotherapy. The primary endpoint was progression-free survival (PFS), which was the interval between recurrence after using PARPi and subsequent recurrence in the case of recurrence. RESULTS:Of 318 patients, 147/318 (46.2%) recurred after the PARPi maintenance. Patients were categorized into groups based on subsequent therapy except non-treated (11/147, 7.5%): platinum-based chemotherapy (89/147, 60.5%), non-platinum-based chemotherapy (21/147, 14.3%), other treatments (26/147, 17.7%), and the median PFS (mPFS) for each group were 7.3, 4.8, and 11.4 months, respectively. Among the platinum-based chemotherapy group, the gemcitabine+carboplatin regimen demonstrated a longer mPFS (10.1 months) than the other regimens (6.6 months, p=0.019). In non-platinum-based chemotherapy, no statistically significant differences were observed among the regimens. And, in the other therapy group, where the proportion of patients with oligometastasis was as high as 88.5%, no significant differences were observed among the therapies, including other modalities. CONCLUSION:In the subsequent chemotherapy of recurrent ovarian cancer after platinum-based chemotherapy and PARPi, the gemcitabine+carboplatin regimen demonstrated a potential to delay recurrence more effectively compared to other therapies.

Though Mica has been used for dysentery, bleeding and inflammation in Ayurveda medicine along with recent evidence on antimicrobial and antitumor effect, the underlying antitumor mechanism of Mica is not fully understood to date. Thus, the antitumor mechanism of processed Mica (PMC) was explored in non-small cell lung cancer cells. Herein PMC showed cytotoxicity and increased sub G1 population in H460 and A549 non-small cell lung cancer cells (NSCLCs). Also, PMC attenuated the expression of pro-PARP, pro-Caspase 3, cdk2, Cyclin A, NRF2, β-catenin, CCR4-NOT transcription complex subunit 2 (CNOT2), c-Myc and s-phase kinase-associated protein 2 (Skp2) compared to untreated control in H460 and A549 cells. Interestingly, CNOT2 was highly expressed at mRNA level in tumor tissues more than in normal tissues with poor prognosis in the patients with lung cancer. Also, TCGA reveals that CNOT2 closely interacts with c-Myc with spearman score of 0.28. Consistently, CNOT2 was bound to c-Myc in H460 cells by Immunoprecipitation and CNOT2 overexpression disturbed the ability of PMC to reduce c-Myc in A549 cells. Also, PMC significantly increased production of reactive oxygen species (ROS) in H460 and A549 cells. Conversely, ROS inhibitor, N-acetyl-l-cysteine (NAC), disturbed the capacity of PMC to reduce pro-PARP, pro-caspase 3, CNOT2 and c-Myc in A549 cells. Furthermore, PMC showed synergistic apoptotic potential with doxorubicin in H460 cells compared to doxorubicin alone by using CompuSyn analysis and SynergyFinder. Overall, these findings suggest that PMC induces apoptosis in lung cancers via inhibition of CNOT2/c-Myc and production of ROS with combinatorial potential with doxorubicin.

In the current work, we investigated the antitumor effects of a 30

ABSTRACTHair follicle stem cells (HFSCs) and dermal papilla cells (DPCs) are crucial in the biogenesis and maintenance of hair follicles (HFs). In this study, a fragment derived from aminoacyl-tRNA synthetase-interacting multifunctional protein1 (AIMP1) was secreted from HFSCs to activate DPCs to maintain hair follicle homeostasis. A histological analysis revealed that AIMP1 levels in hair follicles decreased with hair loss. Hair regrowth in AIMP1-induced mice was faster than that in non-induced mice. Deletion mapping revealed 41 amino acids (TN41, aa 6-46) as the active region of AIMP1. The N-terminal peptide fragment of AIMP1 generated by MMP1 was secreted from Wnt-treated HFSCs to activate DPCs via FGFR2. TN41 activated Akt and ERK, increased β-catenin, and enhanced DPCs activation. TN41 also promoted hair shaft elongation in cultured human hair follicles and improved the hair-inducing activity of cultured DPC spheroids. In summation, the AIMP1 fragment secreted from HFSCs appears to stimulate active hair regrowth through activating DPCs.

Background/Objectives: 3′-Sialyllactose (3′-SL), a human milk oligosaccharide, has anti-inflammatory effects and is demonstrated to have protective effects against osteoarthritis (OA) in vitro and in vivo. However, this hypothesis remains to be investigated in a clinical setting. Herein, we investigated the effects of 3′-SL on pain and physical function in patients with knee OA. Methods: Sixty patients with knee OA with Kellgren and Lawrence grades (KL-grades) 1–4 and Korean Western Ontario and McMaster Universities Osteoarthritis Index (KWOMAC) scores ≥30 were randomly assigned to the placebo (n = 20), 3′-SL 200 mg (n = 20), and 3′-SL 600 mg (n = 20) groups. For 12 weeks, 3′-SL or placebo was administered to patients once a day. Clinical efficacy was evaluated using a visual analog scale (VAS) for pain and KWOMAC for physical function at baseline and at 6 and 12 weeks. Adverse effects were assessed for 12 weeks. Results: Significant reductions in VAS and KWOMAC scores were observed at 12 weeks compared with the baseline in the 3′-SL group. No severe adverse effects were observed over 12 weeks. Conclusions: 3′-SL reduced pain in patients with knee OA, improved daily life movements, and was safe, suggesting that 3′-SL might be an effective treatment for knee OA without severe side effects.

Pancreatic cancer (PC) is a complex malignancy, distinguished by its aggressive characteristics and unfavorable prognosis. Recent developments in understanding the molecular foundations of this disease have brought attention to the noteworthy involvement of microRNAs (miRNAs) in disease development, advancement, and treatment resistance. The anticancer capabilities of flavonoids, which are a wide range of phytochemicals present in fruits and vegetables, have attracted considerable interest because of their ability to regulate miRNA expression. This review provides the effects of flavonoids on miRNA expression in PC, explains the underlying processes, and explores the possible therapeutic benefits of flavonoid-based therapies. Flavonoids inhibit PC cell proliferation, induce apoptosis, and enhance chemosensitivity via the modulation of miRNAs involved in carcinogenesis. Additionally, this review emphasizes the significance of certain miRNAs as targets of flavonoid action. These miRNAs have a role in regulating important signaling pathways such as the phosphoinositide-3-kinase–protein kinase B/Protein kinase B (Akt), mitogen activated protein kinase (MAPK), Janus kinase/signal transducers and activators of transcription (JAK/STAT), and Wnt/β-catenin pathways. This review aims to consolidate current knowledge on the interaction between flavonoids and miRNAs in PC, providing a comprehensive analysis of how flavonoid-mediated modulation of miRNA expression could influence cancer progression and therapy. It highlights the use of flavonoid nanoformulations to enhance stability, increase absorption, and maximize anti-PC activity, improving patient outcomes. The review calls for further research to optimize the use of flavonoid nanoformulations in clinical trials, leading to innovative treatment strategies and more effective approaches for PC.

Although Astragalus membranaceus is known to have anti-inflammatory, anti-obesity, and anti-oxidant properties, the underlying apoptotic mechanism of Astragalus membranaceus extract has never been elucidated in prostate cancer. In this paper, the apoptotic mechanism of a water extract from the dried root of Astragalus membranaceus (WAM) was investigated in prostate cancer cells in association with heat shock protein 27 (HSP27)/androgen receptor (AR) signaling. WAM increased cytotoxicity and the sub-G1 population, cleaved poly (ADP-ribose) polymerase (PARP) and cysteine aspartyl-specific protease 3 (caspase 3), and attenuated the expression of B-cell lymphoma 2 (Bcl-2) in LNCaP cells after 24 h of exposure. Consistently, WAM significantly increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive LNCaP cells. WAM decreased the phosphorylation of HSP27 on Ser82 and inhibited the expression of the AR and prostate-specific antigen (PSA), along with reducing the nuclear translocation of p-HSP27 and the AR via the disturbed binding of p-HSP27 with the AR in LNCaP cells. WAM consistently inhibited the expression of the AR and PSA in dihydrotestosterone (DHT)-treated LNCaP cells. WAM also suppressed AR stability, both in the presence and absence of cycloheximide, in LNCaP cells. Taken together, these findings provide evidence that WAM induces apoptosis via the inhibition of HSP27/AR signaling in prostate cancer cells and is a potent anticancer candidate for prostate cancer treatment.