Article
Chemistry, Medicinal
Pavel Spirin, Elena Shyrokova, Timofey Lebedev, Elmira Vagapova, Polina Smirnova, Alexey Kantemirov, Sergey A. Dyshlovoy, Gunhild von Amsberg, Maxim Zhidkov, Vladimir Prassolov
Summary: Myeloid leukemia can be treated with chemotherapy and stem cell transplantation, but there is a need to optimize treatment outcomes.
Article
Chemistry, Multidisciplinary
Hyeonwoo Je, Gi-Hoon Nam, Gi Beom Kim, Wonjun Kim, Soo Rin Kim, In-San Kim, Eun Jung Lee
Summary: TRAIL shows promising anti-tumor activity, but faces challenges such as resistance and delivery issues. A nanocage has been developed to efficiently deliver TRAIL and a re-sensitizing drug (DOX) to overcome TRAIL-resistant tumors, demonstrating potential as an effective antitumor agent.
JOURNAL OF CONTROLLED RELEASE
(2021)
Review
Biochemistry & Molecular Biology
Longfei Deng, Xuan Zhai, Ping Liang, Hongjuan Cui
Summary: TRAIL holds therapeutic potential in cancer treatment, but many cancers, including GBM, exhibit resistance. Recent studies have identified new mechanisms in regulating TRAIL-induced apoptosis in GBM and effective combinatorial strategies. The TRAIL/TRAIL death receptor axis may have future clinical applications for GBM treatment.
Review
Physiology
Laurel A. Grisanti
Summary: Cardiovascular disease is a leading cause of death globally. Cardiomyocyte death, which occurs in heart damage and stress, contributes to cardiac dysfunction and further damages the heart. Apoptosis, a regulated form of cell death, can occur through intrinsic or extrinsic pathways. The poorly characterized TNF-related ligand TRAIL and its receptors have been found to play a role in cardiac pathology. This article aims to provide an overview of the current understanding of TRAIL and its receptors in normal and pathological conditions in the heart.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Cell Biology
Emir Bozkurt, Heiko Dussmann, Manuela Salvucci, Brenton L. Cavanagh, Sandra Van Schaeybroeck, Daniel B. Longley, Seamus J. Martin, Jochen H. M. Prehn
Summary: The study reveals that TRAIL signaling not only activates apoptosis in colon cancer cells but also induces entosis through TRAIL receptors and the structural presence of caspase-8. The association of TRAIL signaling with cell-in-cell structures is significant in colorectal cancer, especially in the context of patient prognosis. Factors controlling entosis in tumors remain to be elucidated despite the evidence of entosis in cancers.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Cell Biology
Tayyab Shahzad, Cho-Ming Chao, Stefan Hadzic, Judith Behnke, Luisa Biebach, Eva Boettcher-Friebertshaeuser, Jochen Wilhelm, Anne Hilgendorff, Klaus-Peter Zimmer, Rory E. Morty, Saverio Bellusci, Harald Ehrhardt
Summary: Hyperoxia-induced inflammation and tissue damage are crucial steps leading to BPD. TRAIL plays a protective role in lung development, and its depletion leads to structural damage.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Oliver H. Voss, Daniel Arango, Justin C. Tossey, Miguel A. Villalona Calero, Andrea Doseff
Summary: Apigenin sensitizes primary lung cancer cells to TRAIL-induced apoptosis through reprogramming alternative splicing of key TRAIL/DISC components and directly binding heat shock protein 70 to promote cell death. These findings emphasize the synergies between diet and cancer treatments, providing new avenues for improved cancer therapies.
CELL DEATH & DISEASE
(2021)
Article
Pharmacology & Pharmacy
Yu Ren, Xue Wang, Shuaishuai Huang, Yangkai Xu, Guobin Weng, Rui Yu
Summary: In this study, we found that alternol sensitized renal carcinoma cells to TRAIL-induced apoptosis by inhibiting antiapoptotic proteins, upregulating DR5 levels, ROS generation, and the CHOP pathway, thus enhancing TRAIL-mediated apoptosis.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Anderson Luiz-Ferreira, Teresa Pacifico, Alefe Cardoso Cruz, Federica Laudisi, Giovanni Monteleone, Carmine Stolfi
Summary: TRAIL is a promising anticancer agent that selectively induces apoptosis in transformed cells, while flavonoids, natural compounds found in plants, have shown competence in enhancing TRAIL-induced apoptosis. However, bioavailability issues are the main limitations for the clinical use of flavonoids.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Anna-Christina Rambow, Insa Aschenbach, Sofie Hagelund, Doaa Tawfik, Jan-Paul Gundlach, Sebastian Weisse, Nicolai Maass, Anna Trauzold
Summary: Binding of TRAIL to its death domain-containing receptors TRAIL-R1 and TRAIL-R2 can induce cell death and/or pro-inflammatory signaling. The importance of TRAIL and TRAIL-R1/R2 in tumor immune surveillance and cancer biology has meanwhile been well documented. TRAIL also binds to TRAIL-R3 and TRAIL-R4, which have regulatory functions in apoptotic and non-apoptotic signaling pathways. Knockdown of TRAIL-R4 affects the activation of apoptotic and non-apoptotic pathways in cancer cells, showing opposing effects on cell death and clonogenic survival. TRAIL-R4 also regulates the expression of anti-apoptotic proteins and affects the activity of AKT, ERK, p38 and NF-kappa B. This study provides evidence for the important role of endogenous TRAIL-R4 in cancer cells and improves the understanding of the complex TRAIL/TRAIL-R system in humans.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
K. M. A. Zinnah, Sang-Youel Park
Summary: The study demonstrated the mechanism behind the synergistic anticancer effect of amitriptyline and TRAIL, showing that amitriptyline increases TRAIL-induced apoptosis by upregulating death receptors DR4 and DR5. Inhibition of autophagy by amitriptyline was also shown to enhance DR4 and DR5 expression.
Review
Biochemistry & Molecular Biology
You-Take Oh, Shi-Yong Sun
Summary: The involvement of the TRAIL/death receptor signaling pathway in the regulation of cancer invasion and metastasis is complex, with both positive and negative roles reported. The underlying molecular mechanisms are even more complicated. This review focuses on discussing the current understanding of how TRAIL/death receptor-mediated signaling regulates cancer cell invasion and metastasis.
Article
Biochemistry & Molecular Biology
Nadine Kretschmer, Christin Durchschein, Antje Hufner, Beate Rinner, Birgit Lohberger, Rudolf Bauer
Summary: In this study, a novel shikonin derivative called SK119 was synthesized and evaluated for its pharmacological effects on human melanoma cells. SK119 exhibited promising activity in a nano-molar range and showed synergistic effects with vemurafenib and cobimetinib, two clinically used melanoma therapeutics. Further research indicates the potential of SK119 in melanoma therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yudong Yin, Li Sun, Lixin Sheng, Liqiong Zhang, Jingjing Liu, Xiaoan Wen, Weibin Mo, Quande Wang, Keguang Cheng
Summary: To discover more effective and less toxic drugs in anti-tumor field, the backbone structure of 17/?-estradiol was modified and 11 target compounds were synthesized. Compounds 5 and 10 showed better anti-tumor activity and higher selectivity, inducing apoptosis in MCF-7 cells and binding to estradiol receptor alpha. They also upregulated the expression of apoptosis-related factors and downregulated anti-apoptotic factors, indicating the induction of cell death through both endogenous and exogenous pathways.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Pharmacology & Pharmacy
Ting-Li Tang, Yan Yang, Lin Guo, Shuang Xia, Bikui Zhang, Miao Yan
Summary: Experimental findings indicate that Sunitinib induces hepatocellular death primarily by inducing apoptosis and autophagy, with the ROS/MAPKs signaling pathway playing a crucial role. Glycyrrhetinic acid can mitigate Sunitinib-induced cell damage by inhibiting apoptosis and autophagy.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Qiumeng Zhang, Rui Che, Wei Lu
BIOORGANIC & MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Multidisciplinary
Shuangxi Liu, Zonglong Hu, Qiumeng Zhang, Qiwen Zhu, Yi Chen, Wei Lu
Article
Chemistry, Medicinal
Donghuai Xiao, Yu-jie Wang, Han-lin Wang, Yu-bo Zhou, Jia Li, Wei Lu, Jiyu Jin
ARCHIV DER PHARMAZIE
(2020)
Article
Biophysics
Yuliu Zhang, Yi Xiao, Yushu Huang, Yang He, Yanyun Xu, Wei Lu, Jiahui Yu
COLLOIDS AND SURFACES B-BIOINTERFACES
(2020)
Article
Biophysics
Yang He, Yanyun Xu, Yushu Huang, Hao Quang, Xiaoyan Xia, Hongbo Zhao, Yi Xiao, Wei Lu, Jiahui Yu
Summary: In this study, a pH and redox dual-responsive polymer prodrug was developed for the efficient delivery of drugs to metastatic breast cancer cells, leading to inhibition of cancer metastasis to the lung. The nanocapsules showed enhanced drug release under low pH and high redox conditions, as well as active targeting and selectivity to breast cancer cells. Furthermore, the nanocapsules significantly inhibited cell migration and invasion, and suppressed lung metastasis with minimal toxicity.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2022)
Article
Chemistry, Applied
Shulei Zhu, Yingxin Lu, Jiyu Jin, Jiahui Yu, Wei Lu
Summary: A fluorescent probe based on an HSP90 inhibitor was synthesized in this study, showing potential for selective tumor targeting and early diagnosis.
Article
Chemistry, Medicinal
Zhiyang Cheng, Ying Huang, Qianqian Shen, Yangrong Zhao, Lei Wang, Jiahui Yu, Wei Lu
Summary: The study presented an albumin-based drug delivery system, synthesized an antitumor prodrug Mal-glu-CPTS0001, and demonstrated its in vivo antitumor effects. The prodrug covalently binds to plasma albumin, releases the drug in tumors, and achieves reduced toxicity and enhanced selectivity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Ying Huang, Lei Wang, Zhiyang Cheng, Biyu Yang, Jiahui Yu, Yi Chen, Wei Lu
Summary: The novel Mal-glu-SN38 prodrug showed selective delivery of SN38 to tumour sites and enhanced efficacy. With slower plasma clearance, increased drug exposure over time, and enhanced accumulation at the tumour site, Mal-glu-SN38 significantly delayed tumour growth after multiple doses, leading to an impressive reduction or even disappearance of tumours without observable side effects in 67% of mice.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Biochemistry & Molecular Biology
Shuting Wang, Shulei Zhu, Yawen Tanzeng, Yuexing Zhang, Chuchu Li, Mingliang Ma, Wei Lu
Summary: A series of novel near-infrared fluorescent molecules were designed with a compact donor-acceptor-donor architecture, exhibiting significant variations in fluorescence intensity and viscosity sensitivity in different solvent polarities. Among them, one molecule M-3 showed a 3-fold increase in emission intensity in a high viscosity solvent system and a 4-fold increase in fluorescence intensity in the presence of proteins, demonstrating superior environmental sensitivity and potential for optical imaging probe development.
Article
Biochemistry & Molecular Biology
Yingxin Lu, Danwen Sun, Donghuai Xiao, Yingying Shao, Mingbo Su, Yubo Zhou, Jia Li, Shulei Zhu, Wei Lu
Summary: Novel CRBN-recruiting HDAC PROTACs were designed and synthesized, with 21a showing excellent activity and demonstrating the potential of the benzyl alcohol linker. These PROTACs exhibited outstanding inhibitory activity on different HDAC classes and showed better anti-proliferative activity on the MM.1S cell line.
Article
Biochemistry & Molecular Biology
Tingting He, Shulei Zhu, Wei Lu
Summary: Heat shock protein 90 (HSP90) is a promising target for anticancer drugs. In this study, a series of novel HSP90 inhibitors was synthesized and compound 6u exhibited the most potent anti-proliferative activity, particularly in Capan-1 cell line. Molecular modeling studies also confirmed the interaction mechanism between 6u and HSP90, suggesting it as a potential candidate for further research.
MOLECULAR DIVERSITY
(2023)
Article
Biochemistry & Molecular Biology
Longjun Ma, Yan Zhou, Dehua Yang, Ming-Wei Wang, Wei Lu, Jiyu Jin
Summary: Hydroxymethylthiohydantoin, hydroxymethylthiohydantoin, and hydantoin, all containing a pyridine group, were synthesized to investigate their androgen receptor antagonistic activities. Among them, compounds 6a/6c/7g/19a/19b showed remarkable antagonistic activity against the androgen receptor, comparable to or even surpassing enzalutamide. Additionally, compounds 19a and 19b exhibited superior antiproliferative activity compared to enzalutamide in prostate cancer cells. These findings suggest that compound 19a holds promising potential as a novel AR antagonist.
Article
Biochemistry & Molecular Biology
Mengyuan Ding, Yingying Shao, Danwen Sun, Suorina Meng, Yi Zang, Yubo Zhou, Jia Li, Wei Lu, Shulei Zhu
Summary: This study designed and synthesized a series of small molecule BRD4 PROTACs, among which 8b could effectively degrade BRD4 and has the potential for treating related diseases such as leukemia, multiple myeloma, and pulmonary fibrosis.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Shulei Zhu, Jieyu Liu, Donghuai Xiao, Peipei Wang, Jingkun Ma, Xiaobei Hu, Jingfeng Fu, Yubo Zhou, Jia Li, Wei Lu
Summary: This study reports a novel Wee1 degrader based on PROTAC technology, which effectively degrades cellular Wee1 protein and has potential applications in cancer therapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Zhiyang Cheng, Ying Huang, Pingxuan Shao, Lei Wang, Shulei Zhu, Jiahui Yu, Wei Lu
Summary: Stimulus-responsive albumin-based prodrugs offer a promising drug delivery strategy for targeted and controlled release in tumor microenvironments, with hypoxia-activated Mal-azoExatecan showing potential for specific tumor targeting and release control.
Review
Oncology
Xinru Zhou, Yin Jia, Chuanbin Mao, Shanrong Liu
Summary: Small extracellular vesicles (sEVs), such as exosomes, have emerged as crucial targets for liquid biopsy and promising drug delivery vehicles in tumor progression. They can serve as biomarkers for tumor diagnosis and as drug carriers for cancer treatment.
Article
Oncology
Ruochan Chen, Ju Zhu, Xiao Zhong, Jie Li, Rui Kang, Daolin Tang
Summary: The interplay between autophagy and apoptosis plays a crucial role in tumorigenesis and cancer therapy, with HMGB1 serving as a key regulator in these processes.
Article
Oncology
Zongfu Pan, Xixuan Lu, Tong Xu, Jinming Chen, Lisha Bao, Ying Li, Yingying Gong, Yulu Che, Xiaozhou Zou, Zhuo Tan, Ping Huang, Minghua Ge
Summary: This study uncovered the emerging role of HN1 in promoting dedifferentiation of anaplastic thyroid cancer (ATC) cells. HN1 negatively regulated the thyroid differentiation markers and had an inhibitory effect on the transcriptional activation of CTCF, thereby influencing the chromatin accessibility of thyroid differentiation genes.
Article
Oncology
Yi Qin, Shengjun Xiong, Jun Ren, Gautam Sethi
Summary: Autophagy plays an important regulatory role in glioblastoma, and its dysregulation can lead to drug resistance and radioresistance. It also affects stem cell characteristics, overall growth, and metastasis. Therefore, autophagy is a promising target for glioblastoma therapy.
Article
Oncology
Katsuya Nagaoka, Xuewei Bai, Dan Liu, Kevin Cao, Joud Mulla, Chengcheng Ji, Hongze Chen, Muhammad Azhar Nisar, Amalia Bay, William Mueller, Grace Hildebrand, Jin-Song Gao, Shaolei Lu, Hiroko Setoyama, Yasuhito Tanaka, Jack R. Wands, Chiung-Kuei Huang
Summary: This study found that serum 2-OG levels in cholangiocarcinoma patients are associated with the effectiveness of chemotherapy. Patients with progressive disease showed significantly higher levels of serum 2-OG compared to stable disease and partial response patients. The study also revealed that overexpression of ASPH mimics the effects of 2-OG, and knockdown of ASPH improves chemotherapy. Targeting ASPH enhances the effects of chemotherapy by modulating ATM and ATR, two key regulators of DDRs.
