Autophagy modulating agents as chemosensitizers for cisplatin therapy in cancer

Published on Apr 1, 2021in Investigational New Drugs3.85
· DOI :10.1007/S10637-020-01032-Y
Bartosz Gąsiorkiewicz2
Estimated H-index: 2
(Jagiellonian University Medical College),
Paulina Koczurkiewicz-Adamczyk4
Estimated H-index: 4
(Jagiellonian University Medical College)
+ 1 AuthorsElżbieta Pękala19
Estimated H-index: 19
(Jagiellonian University Medical College)
Although cisplatin is one of the most common antineoplastic drug, its successful utilisation in cancer treatment is limited by the drug resistance. Multiple attempts have been made to find potential cisplatin chemosensitisers which would overcome cancer cells resistance thus improving antineoplastic efficacy. Autophagy modulation has become an important area of interest regarding the aforementioned topic. Autophagy is a highly conservative cellular self-digestive process implicated in response to multiple environmental stressors. The high basal level of autophagy is a common phenomenon in cisplatin-resistant cancer cells which is thought to grant survival benefit. However current evidence supports the role of autophagy in either promoting or limiting carcinogenesis depending on the context. This encourages the search of substances modulating the process to alleviate cisplatin resistance. Such a strategy encompasses not only simple autophagy inhibition but also harnessing the process to induce autophagy-dependent cell death. In this paper, we briefly describe the mechanism of cisplatin resistance with a special emphasis on autophagy and we give an extensive literature review of potential substances with cisplatin chemosensitising properties related to autophagy modulation.
#1Xinyu Li (PRC: China Medical University (PRC))H-Index: 6
#2Yong Zhou (PRC: China Medical University (PRC))H-Index: 2
Last. Hangyu Li (PRC: China Medical University (PRC))H-Index: 19
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Abstract The success of targeted drug therapy for cancer patients has attracted extensive attention from academia and society. However, the rapid development of acquired drug resistance is becoming a major challenge. Autophagy, as an essential homeostatic and catabolic process, is crucial for the degradation or recycling of proteins and cellular components. Autophagy has a crucial role in several cellular functions and its dysregulation is associated with tumorigenesis, tumor–stroma interactions...
#1Iva Potočnjak (University of Rijeka)H-Index: 11
#2Lidija Šimić (University of Rijeka)H-Index: 3
Last. Robert Domitrović (University of Rijeka)H-Index: 23
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Abstract Oleanolic acid (OA) is a natural triterpenoid that possesses numerous beneficial health effects such as antioxidant, anti-inflammatory and anti-apoptotic activities. In this study, we investigated the therapeutic effect of OA (10 and 40 mg/kg) on cisplatin (CP)-induced (13 mg/kg) nephrotoxicity. Treatment with OA 40 mg/kg once daily for 2 days, 48 h after CP-intoxication, ameliorated the increased serum markers and histological features of kidney injury. CP administration increased rena...
#1Yaxian ZhaoH-Index: 1
#2Huanjun Xia (Jining Medical University)H-Index: 1
Abstract Background Cisplatin resistance has been found to contribute to the failure of ovarian carcinoma treatment. Oridonin is a natural en-kaurane tetracyclic diterpenoid compound discovered in Rabdosia rubescene (Henmsl.) Hara. Herein, we tested whether oridonin could exert chemo-sensitization activity on cisplatin-resistant ovarian carcinoma cells. Methods Firstly, A2780CP cells and SKOV3/DDP cells were exposed to cisplatin and/or oridonin treatment. Cell counting kit-8 (CCK-8) kit and Dead...
#1Jennifer Bryant (University of Birmingham)H-Index: 4
#2Nikolaos Batis (University of Birmingham)H-Index: 7
Last. Hisham MehannaH-Index: 47
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// Jennifer Bryant 1 , * , Nikolaos Batis 1 , * , Anna Clara Franke 1 , Gabriella Clancey 1 , Margaret Hartley 1 , Gordon Ryan 1 , Jill Brooks 1 , Andrew D. Southam 4 , 5 , Nicholas Barnes 2 , 7 , Joanna Parish 2 , Sally Roberts 2 , Farhat Khanim 6 , Rachel Spruce 1 , # and Hisham Mehanna 1 , 3 , # 1 Institute of Head and Neck Studies and Education (InHANSE), University of Birmingham, Birmingham, UK 2 Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of...
#1Shang Hung Chen (NCKU: National Cheng Kung University)H-Index: 1
#2Jang Yang Chang (NCKU: National Cheng Kung University)H-Index: 61
Although cisplatin has been a pivotal chemotherapy drug in treating patients with various types of cancer for decades, drug resistance has been a major clinical impediment. In general, cisplatin exerts cytotoxic effects in tumor cells mainly through the generation of DNA-platinum adducts and subsequent DNA damage response. Accordingly, considerable effort has been devoted to clarify the resistance mechanisms inside tumor cells, such as decreased drug accumulation, enhanced detoxification activit...
#1Huahong Yang (JLU: Jilin University)H-Index: 1
#2Yun Gao (JLU: Jilin University)H-Index: 3
Last. Xinxin Ci (JLU: Jilin University)H-Index: 25
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AMPK-mediated autophagy and Akt/mTOR pathways play important roles in current cancer treatments. Oridonin (Ori), an ent-kaurane diterpenoid isolated from Isodon rubescens, exerts extensive anti-tumor potential and controversial effects on autophagy. In this study, we investigated the effect of Ori on the autophagy, apoptosis, and AMPK/Akt/mTOR pathways and determined whether Ori was related to the increased cisplatin sensitivity observed in A549 cells. First, we found that Ori suppressed Akt/mTO...
#1Alexey V. Morozov (EIMB: Engelhardt Institute of Molecular Biology)H-Index: 10
#2Vadim L. Karpov (EIMB: Engelhardt Institute of Molecular Biology)H-Index: 19
The life of every organism is dependent on the fine-tuned mechanisms of protein synthesis and breakdown. The degradation of most intracellular proteins is performed by the ubiquitin proteasome system (UPS). Proteasomes are central elements of the UPS and represent large multisubunit protein complexes directly responsible for the protein degradation. Accumulating evidences indicate that there is an intriguing diversity of cellular proteasomes. Different proteasome forms, containing different subu...
#1Jia-Jun Li (Guangzhou Medical University)H-Index: 8
#2Yanyan Yan (SDU: Shanxi Datong University)H-Index: 7
Last. Jianye Zhang (Guangzhou Medical University)H-Index: 16
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As a a quinonemethide triterpenoid extracted from species of the Celastraceae and Hippocrateaceae, pristimerin has been shown to have potent anti-cancer effects. Specifically, it was found that pristimerin can affect many tumor-related processes including vasculogenesis, autophagy, epithelial-mesenchymal transition and ubiquitin-proteasomal degradation, as well as involving various molecular targets and signaling pathways such as cyclins, reactive oxygen species caspase-3, and NF-κB, MAPK/ERK an...
#1Sumit Ghosh (IITK: Indian Institute of Technology Kanpur)H-Index: 2
Abstract Cisplatin or (SP-4-2)-diamminedichloridoplatinum(II) is one of the most potential and widely used drugs for the treatment of various solid cancers such as testicular, ovarian, head and neck, bladder, lung, cervical cancer, melanoma, lymphomas and several others. Cisplatin exerts anticancer activity via multiple mechanisms but its most acceptable mechanism involves generation of DNA lesions by interacting with purine bases on DNA followed by activation of several signal transduction path...
#1Samprikta MannaH-Index: 2
#2Cathal McCarthy (UCC: University College Cork)H-Index: 17
Last. Fergus P. McCarthyH-Index: 25
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Preeclampsia is a multisystemic pregnancy disorder and a major cause of maternal and neonatal morbidity and mortality worldwide. The exact pathophysiology of preeclampsia remains unclear; however, it is speculated that the various pathologies can be attributed to impaired vascular remodelling and elevated oxidative stress within the placenta. Oxidative stress plays a key role in cell ageing, and the persistent presence of elevated oxidative stress precipitates cellular senescence and mitochondri...
Cited By6
#10Xia Liu (MOE: Chinese Ministry of Education)H-Index: 1
#1Asal Jalal Abadi (IAU: Islamic Azad University)H-Index: 2
#2Sepideh Mirzaei (IAU: Islamic Azad University, Science and Research Branch, Tehran)H-Index: 11
Last. Gautam Sethi (NUS: National University of Singapore)H-Index: 116
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Curcumin is a phytochemical isolated from Curcuma longa with potent tumor-suppressor activity, which has shown significant efficacy in pre-clinical and clinical studies. Curcumin stimulates cell death, triggers cycle arrest, and suppresses oncogenic pathways, thereby suppressing cancer progression. Cisplatin (CP) stimulates DNA damage and apoptosis in cancer chemotherapy. However, CP has adverse effects on several organs of the body, and drug resistance is frequently observed. The purpose of the...
#1Changcheng Wang (Peking Union Medical College)
#2Jia Guo (Peking Union Medical College)
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Traditional Chinese medicine Curcuma zedoary has been used for treating various diseases and cancers. However, the therapeutic effect of Curdione, one of its major components in triple negative breast cancer (TNBC) is still obscure. This study is aimed to explore whether combination of Curdione and docetaxel (DTX) could strengthen the DTX-induced pro-apoptotic effects in TNBC cells and identify its involved signaling pathways. In this study, combination of Curdione and DTX intensified the inhibi...
#1Maciej Sobczak (Hong Kong Environmental Protection Department)
Lung cancer is one of the most lethal types of cancer due to a lack of proper treatment. The rare presence of molecular therapy targets forces the use of platinum-based drugs. Cisplatin, approved by the USA as an anticancer therapy in the 1970s, is still one of the most prominent therapies against lung cancer. Unfortunately, the biggest limitation of cisplatin-based therapy is the development of cisplatin resistance. Cancer cells overcome the vast DNA damage caused by the drug in a variety of wa...
#1K.M.A. Zinnah (CBNU: Chonbuk National University)H-Index: 3
#2Sang-Youel Park (CBNU: Chonbuk National University)H-Index: 28
Tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) is a cytokine with the potential to induce cancer cell‑specific apoptosis with minimal toxicity to normal cells. Therefore, the resistance of certain cancer cells to TRAIL is a major concern and agents that can either enhance TRAIL capabilities or overcome TRAIL resistance are necessary for the development of cancer treatments. The present study investigated whether the antidepressant drug amitriptyline could sensitize TRAIL‑resista...
Clinical outcomes of conventional drug combinations are not ideal due to high toxicity to healthy tissues. Cisplatin (CDDP) is the standard component for many cancer treatments, yet its principal dose-limiting side effect is nephrotoxicity. Thus, CDDP is commonly used in combination with other drugs, such as the autophagy inhibitor chloroquine (CQ), to enhance tumor cell killing efficacy and prevent the development of chemoresistance. In addition, nanocarrier-based drug delivery systems can over...
#1Sepideh MirzaeiH-Index: 11
#2Kiavash HushmandiH-Index: 15
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The failure of chemotherapy is a major challenge nowadays, and in order to ensure effective treatment of cancer patients, it is of great importance to reveal the molecular pathways and mechanisms involved in chemoresistance. Cisplatin (CP) is a platinum-containing drug with anti-tumor activity against different cancers in both pre-clinical and clinical studies. However, drug resistance has restricted its potential in the treatment of cancer patients. CP can promote levels of free radicals, parti...
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