Review
Biochemistry & Molecular Biology
Anna Fontana, Ilaria Cursaro, Gabriele Carullo, Sandra Gemma, Stefania Butini, Giuseppe Campiani
Summary: HDAC8, an important enzyme, plays a role in various diseases and selective HDAC8 inhibitors are being developed. Polypharmacological approaches have also been explored.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Huijun Zhang, Xiangwei Wang, Min Qu, Zhiyong Li, Xiangping Yin, Lijie Tang, Xiangtao Liu, Yuefeng Sun
Summary: This study reveals that histone deacetylase 8 (HDAC8) inhibits the replication of foot-and-mouth disease virus (FMDV) by regulating innate immune signal transduction and antiviral response. In response, FMDV utilizes autophagy to promote the degradation of HDAC8. Further investigations demonstrate that FMDV structural protein VP3 promotes autophagy during virus infection, interacting with and degrading HDAC8 through an AKT-MTOR-ATG5-dependent autophagy pathway. These findings highlight a strategy employed by FMDV to counteract host antiviral activity through autophagic degradation of a protein involved in innate immune response.
Article
Chemistry, Medicinal
Hualong Mo, Ruiqiang Zhang, Yajun Chen, ShuTing Li, Yao Wang, Wenbo Zou, Qiman Lin, Deng-Gao Zhao, Yarong Du, Kun Zhang, Yan-Yan Ma
Summary: Compound 21 is an effective anticancer agent that inhibits tumor growth by inhibiting autophagy and inducing cell apoptosis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Chandra Sekhar Bhol, Soumya Ranjan Mishra, Shankargouda Patil, Sunil Kumar Sahu, R. Kirtana, Soumen Manna, Muthu Kumaraswamy Shanmugam, Gautam Sethi, Samir Kumar Patra, Sujit Kumar Bhutia
Summary: Procaine inhibits DNA methylation by suppressing DNMT activity and increases the expression of PAX9 in oral squamous cell carcinoma cells, triggering an anticancer mechanism and potentially offering a new therapeutic strategy for OSCC.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Multidisciplinary Sciences
Ting Guo, Shaohua Hu, Weijue Xu, Jin Zhou, Feng Chen, Tingting Gao, Wenqian Qu, Faling Chen, Zhibao Lv, Li Lu
Summary: This study found that histone deacetylase 8 (HDAC8) plays an important role in modulating arginine metabolism during the development of necrotizing enterocolitis (NEC) by regulating the acetylation of histone 3 lysine 9 (acetyl-H3K9). The upregulation of HDAC8 was observed in samples from humans and mice with NEC, and selective inhibition of HDAC8 expression improved NEC. HDAC8 was found to regulate enzymes involved in the metabolic conversion of proline to arginine and arginine to ornithine, and the signal of H3K9ac in the promoter region of PRODH/PRODH2 was mediated by HDAC8. A decreased concentration of butyric acid was correlated with elevated HDAC8 levels and circulating arginine, suggesting an unbalanced Firmicutes/Bacteroidetes ratio.
Article
Oncology
Wei Zhao, Chen Chen, Jianjun Zhou, Xiaoqing Chen, Kuan Cai, Miaomiao Shen, Xuan Chen, Lei Jiang, Guodong Wang
Summary: In this study, it was found that metformin inhibits cell proliferation in Oral Squamous Cell Carcinoma (OSCC) by promoting apoptosis and blocking the cell cycle, and inhibiting autophagy with hydroxychloroquine (HCQ) enhances the anti-tumor effect of metformin. Metformin combined with HCQ may become a safe and effective treatment strategy for OSCC.
Article
Chemistry, Medicinal
An-Min Zhou, Meng-Meng Wang, Yan Su, Zheng-Hong Yu, Hong-Ke Liu, Zhi Su
Summary: In this study, a new agent Ir-VPA was developed, which exhibited switching between apoptosis and autophagy in cervical cancer cells due to the inhibition of HDAC6 at different levels. Ir-VPA showed the best anticancer activity to HeLa cells, inducing severe DNA damages and cell cycle arrest at G2/M phase. The anticancer mechanism of Ir-VPA was dependent on the inhibitory performance of HDAC6, with caspase-dependent apoptosis at low concentration and autophagy with autophagy flux blockage at high concentration.
Article
Biochemistry & Molecular Biology
Chunlong Zhao, Deng Chen, Fengzhi Suo, Rita Setroikromo, Wim J. Quax, Frank J. Dekker
Summary: Aberrations in HDAC8 functions are closely linked to various diseases, and development of HDAC8 degradation inducers may be more promising than HDAC8 inhibitors. Using the PROTAC strategy, we developed a selective and potent HDAC8 degradation inducer CT-4 with single-digit nano-molar DC50 values and over 95% Dmax in both MDA-MB-231 cells and T-cell leukemia cells. CT-4 showed potent anti-migration activity and limited anti-proliferative activity in MDA-MB-231 cells, while effectively inducing apoptotic cell death in Jurkat cells. These findings suggest that the development of HDAC8 degradation inducers holds great potential for the treatment of HDAC8-related diseases.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ryosuke Ushio, Miki Hiroi, Ari Matsumoto, Kazumasa Mori, Nobuharu Yamamoto, Yoshihiro Ohmori
Summary: The combined treatment of DNMTis, HMTis, and HDACis in epigenomic therapy effectively reduces the viability of oral squamous cell carcinoma cells by inducing apoptosis and cell cycle arrest in the S and G2/M phases.
Article
Cell Biology
Jierong Chen, Lixue Cao, Jianhong Ma, Caifeng Yue, Dandan Zhu, Ran An, Xiaoxiao Wang, Yunmiao Guo, Bing Gu
Summary: This study reveals the critical role of the HDAC8/IRF1/SUCNR1 axis in colorectal cancer (CRC), with implications in cell growth, autophagy, and liver metastasis.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2022)
Article
Oncology
Xiao-Tian Jiang, Ye Qiu, Cong-Hua LI
Summary: This study found that cryptotanshinone, a compound isolated from the Chinese herb Salvia miltiorrhiza, can significantly induce apoptosis and inhibit proliferation in oral squamous cell carcinoma (OSCC). It induces cell autophagy through the activation of the LC3 pathway, and has shown significant antitumor effects in a tumor xenograft model.
Article
Oncology
Weihong Xie, Lijuan Xu
Summary: USP14 is identified as a key regulator of radioresistance in oral squamous cell carcinoma (OSCC), with high expression predicting poor survival. Knockdown of USP14 enhances DNA damage and apoptosis induced by radiation, inhibits cell proliferation.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Oncology
Zhi-Hang Zhou, Tong-Chao Zhao, Si-Yuan Liang, Zhi-Yuan Zhang, Dong-Wang Zhu, Wu-Tong Ju, Lai-Ping Zhong
Summary: The combination therapy of Interferon-gamma and autophagy inhibitor (chloroquine) has shown significant efficacy in oral squamous cell carcinoma, promoting apoptosis and inhibiting cellular growth. Interferon-gamma-induced autophagy plays a protective role in oral squamous cell carcinoma cells, while blocking autophagy flux can enhance Interferon-gamma-mediated apoptosis. This novel strategy represents a promising approach for oral squamous cell carcinoma therapy.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Chemistry, Medicinal
Nan Sun, Kexin Yang, Wenzhong Yan, Mingyue Yao, Chengying Xie, Jianjun Cheng, Chengcheng Yu, Wenwen Duan, Xiaoke Gu, Dong Guo, Hualiang Jiang
Summary: Compound 19h, a novel HDAC inhibitor, showed potent and selective inhibition of HDAC1 and exhibited good antiproliferative activity in vitro. It significantly inhibited the growth of human tumor xenografts and murine tumor in animal models. When combined with the mPD-1 antibody, 19h increased the ratio of splenic CD4+ T effector cells and promoted complete tumor regression in 5/6 animals in the MC38 model. These findings suggest that selective class I HDAC inhibitors have direct tumor growth inhibition and indirect immune cell-mediated antitumor effects, and synergize with immune checkpoint inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Dentistry, Oral Surgery & Medicine
Thi Thuy Tien Vo, Yinshen Wee, Hsin-Chung Cheng, Ching-Zong Wu, Yuh-Lien Chen, Vo Phuoc Tuan, Ju-Fang Liu, Wei-Ning Lin, I-Ta Lee
Summary: This study investigated the anticancer effects and underlying mechanisms of surfactin on human oral squamous cell carcinoma (OSCC). The results showed that surfactin could induce apoptosis, autophagy, and cell cycle arrest through different signaling pathways. The study suggests that surfactin may serve as a multifaceted anticancer agent for OSCC.