Evidence map›Paper›PMID 39318019›Full record

ArticleCurrent cancer drug targets2025

Deoxypodophyllotoxin Mediates Autophagy Death through Inhibition of GRP78 in Human Osteosarcoma.

Xiao-Jun Tang, Ling-Li Luo, Wenchao Zhou, Gang-Qing Shi, Xiao-Xu Wang, Tian Zeng, Xiong-Jin Tan, Wei-Ming Guo, An-Bo Gao, Yukun Li and 1 more

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Article in Current cancer drug targets, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Xiao-Jun TangThe Second Affiliated Hospital, Department of Spinal Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
Ling-Li LuoMedical College, Hunan Polytechnic of Environment and Biology, Hengyang, 421005, Hunan Province, China.
Wenchao ZhouHunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, University of South China, Hengyang, 421001, Hunan Province, China.
Gang-Qing ShiHunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, University of South China, Hengyang, 421001, Hunan Province, China.
Xiao-Xu WangThe Second Affiliated Hospital, Department of Joint Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
Tian ZengHunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, University of South China, Hengyang, 421001, Hunan Province, China.
Xiong-Jin TanThe Second Department of Orthopaedic, 922 Hospital of PLA, Hengyang, Hunan, 410011, China.
Wei-Ming GuoThe Second Affiliated Hospital, Department of Joint Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
An-Bo GaoClinical Research Institute, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Yukun LiDepartment of Assisted Reproductive Centre, Zhuzhou Central Hospital, Xiangya Hospital Zhuzhou Central South University, Central South University, Zhuzhou, Hunan, China.
Juan ZouHunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, University of South China, Hengyang, 421001, Hunan Province, China.

Funding

Hunan Provincial Natural Science Foundation of China 2022JJ30519Scientific Research Fund of Hengyang Science and Technology Bureau 2019jh010988Scientific Research Fund of Hunan Provincial Education Department 21C1121Scientific Research Fund of Hunan Provincial Health Commission 20200968
6 · The paper itself

Abstract

backgroundGlucose-regulated protein 78 (GRP78), as a chaperone protein, can protect the endoplasmic reticulum of cells and is expressed to influence chemoresistance and prognosis in cancer. Deoxypodophyllotoxin (DPT) is a compound with antitumor effects on cancers. DPT inhibits the proliferation of osteosarcoma by inducing apoptosis, necrosis, or cell cycle arrest.

objectivesThis study was performed to demonstrate the molecular mechanism by which DPT attenuates osteosarcoma progression through GRP78.

methodsNatural compound libraries and western blot (WB) were used to screen the inhibitors of osteosarcoma GRP78. The expression of mitochondria-related genes in cancer cells of the treatment group was detected by quantitative real-time PCR (qPCR) and WB. 3-(4,5)- Dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and 5-ethynyl-2'- deoxyuridine (EDU) were used to discover the activity and proliferation of osteosarcoma cells treated with DPT. We constructed an

resultsDPT inhibited osteosarcoma cell survival and the growth of tumor xenografts. It promoted up-regulation of BCL2-associated X protein (Bax) and B-cell CLL/lymphoma 2 (Bcl-2), which serves to mediate and attenuate, respectively, the killing activities of DPT through mitochondria dysfunction. The effect of DPT against cancer cells could be attenuated by the overexpression of GRP78, characterized by the inactivation of the caspase cascade. The loss of GRP78 in osteosarcoma cells negatively mediated the basal level of autophagyassociated genes. DPT stimulated autophagy via the phosphoinositide 3-kinase (PI3K)-v-akt murine thymoma viral oncogene homolog (AKT), a mechanistic target of rapamycin (mTOR) axis. The autophagy caused by DPT played an active role in the osteosarcoma of humans and blocked the apoptotic cascade.

conclusionCombination treatment with the GRP78 inhibitor DPT and pharmacological autophagy inhibitors will be a meaningful method of obviating osteosarcoma cells.

Indexed as

AutophagyBone NeoplasmsHeat-Shock ProteinsOsteosarcomaPodophyllotoxinAnimalsApoptosisCell Line, TumorCell ProliferationDrugs, Chinese HerbalEndoplasmic Reticulum Chaperone BiPHumansMiceMice, Inbred BALB CMice, NudeXenograft Model Antitumor AssaysdeoxypodophyllotoxinDrugs, Chinese HerbalEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsHSPA5 protein, humanHspa5 protein, mousePodophyllotoxinapoptosisautophagycombination treatment.DPTGRP78osteosarcoma

Identifiers

PMID39318019

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.