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Liver cancer such as hepatocellular carcinoma (HCC) is one of the most common causes of cancer deaths globally and shows resistance to several anticancer drugs. Despite the rising incidence and poor prognosis of malignant HCC, the underlying molecular mechanisms driving this aggressive cancer remain unclear. Several natural compounds, such as phytochemicals of dietary and non-dietary origin, affect hepatocarcinogenesis signaling pathways in vitro and in vivo, which may help prevent and treat HCC cells. Current HCC cells treatments include chemotherapy, radiation, and surgery. However, these standard therapies have substantial side effects, and combination therapy enhances side effects for an acceptable therapeutic benefit. Therefore, there is a need to develop treatment strategies for HCC cells that are more efficacious and have fewer adverse effects. Multiple genetic and epigenetic factors are responsible for the HCC cells to become resistant to standard treatment. Autophagy contributes to maintain cellular homeostasis, which activates autophagy for biosynthesis and mitochondrial regulation and recycling. Therefore, modifying autophagic signaling would present a promising opportunity to identify novel therapies to treat HCC cells resistant to current standard treatments. This comprehensive review illustrates how natural compounds demonstrate their anti-hepatocellular carcinoma function through autophagy.<\/jats:p>","DOI":"10.3390\/cells13141186","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T08:16:57Z","timestamp":1720772217000},"page":"1186","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Advancements in Utilizing Natural Compounds for Modulating Autophagy in Liver Cancer: Molecular Mechanisms and Therapeutic Targets"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6649-3694","authenticated-orcid":false,"given":"Md Ataur","family":"Rahman","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4126-8751","authenticated-orcid":false,"given":"S M","family":"Rakib-Uz-Zaman","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA"},{"name":"Biotechnology Program, Department of Mathematics and Natural Sciences, School of Data and Sciences, BRAC University, Dhaka 1212, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9553-7246","authenticated-orcid":false,"given":"Somdeepa","family":"Chakraborti","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7564-2078","authenticated-orcid":false,"given":"Sujay Kumar","family":"Bhajan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology & Genetic Engineering, Bangabandhu Sheikh Mujibur Rahman Science & Technology University, Gopalganj 8100, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-676X","authenticated-orcid":false,"given":"Rajat Das","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4726-0507","authenticated-orcid":false,"given":"Maroua","family":"Jalouli","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0246-3872","authenticated-orcid":false,"given":"Md. Anowar Khasru","family":"Parvez","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Jahangirnagar University, Savar 1342, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9953-3939","authenticated-orcid":false,"given":"Mushfiq H.","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head & Neck Surgery, Western University, London, ON N6A 4V2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6840-3787","authenticated-orcid":false,"given":"Ehsanul","family":"Hoque Apu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Dental Medicine, Lincoln Memorial University, Knoxville, TN 37923, USA"},{"name":"DeBusk College of Osteopathic Medicine, Lincoln Memorial University, Harrogate, TN 37752, USA"},{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2170-1303","authenticated-orcid":false,"given":"Abdel Halim","family":"Harrath","sequence":"additional","affiliation":[{"name":"Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungjoon","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Korean Medicine, Kyung Hee University, 1\u20135 Hoegidong Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8678-156X","authenticated-orcid":false,"given":"Bonglee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Korean Medicine, Kyung Hee University, 1\u20135 Hoegidong Dongdaemun-gu, Seoul 02447, Republic of Korea"},{"name":"Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"174891","DOI":"10.1016\/j.ejphar.2022.174891","article-title":"Rebamipide attenuates alcohol-induced gastric epithelial cell injury by inhibiting endoplasmic reticulum stress and activating autophagy-related proteins","volume":"922","author":"He","year":"2022","journal-title":"Eur. 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