Talks
Presenting Author Academic/Professional Position
Post-doc
Academic Level (Author 1)
Post-doc
Discipline/Specialty (Author 1)
Immunology and Microbiology
Academic Level (Author 5)
Faculty
Discipline/Specialty (Author 5)
Immunology and Microbiology
Presentation Type
Oral Presentation
Discipline Track
Biomedical Science
Abstract Type
Research/Clinical
Abstract
Background: The liver is the principal organ responsible for the detoxification of exogenous and endogenous toxins, xenobiotics, and viruses and bacteria, making it susceptible to damage by various chemicals and metabolites that enter the body. In clinical relevance, Hepatocellular carcinoma (HCC) is a major global health concern, being the sixth most common cancer worldwide and third leading cause of cancer-related death. HCC accounts for 85–90% of liver cancers globally. Texas is projected to have the second-highest liver cancer-related deaths, with Hispanic populations experiencing the highest mortality rates. The liver, a vital metabolic organ, is particularly vulnerable to stress-induced damage. According to the ACS 2024, the USA is expected to report 41,630 new cases and 29,840 deaths from HCC. In the South Texas Rio Grande Valley (RGV), where ~90% of the population is Latino/Hispanic, socioeconomic disparities, poverty, obesity, diabetes, and low-income levels contribute to a high prevalence of stress. Stress exacerbates cancer progression by impairing immune responses, triggering inflammation, and activating the Hypothalamic-Pituitary-Adrenal (HPA) axis, which releases cortisol and leptin, known to influence oncogenesis. These stressors can significantly affect liver function, hastening HCC progression. Critical need for targeted therapies in stress-associated HCC growing importance of natural compounds in cancer treatment, Silymarin as a promising hepatoprotective agent in HCC. The therapeutic Potential of Silymarin, a flavonolignan complex derived from Silybum marianum (milk thistle), has demonstrated hepatoprotective and anticancer properties. Its historical use in liver diseases, such as cirrhosis and hepatitis, underscores its potential as a therapeutic agent in HCC. Studies indicate its antioxidant, anti-inflammatory, and anti-fibrotic properties, which are essential in mitigating stress-induced liver damage.
Methods: Proteins, pathways associated with stress were identified through liquid chromatography-mass spectrometry (LC-MS) and analysis the data by proteome discoverer 2.5 software. HCC cell lines were treated with cortisol and leptin to simulate acute and chronic stress conditions. Gene expression was analyzed via reverse transcription-polymerase chain reaction (RT-PCR), and overexpression models were established using lentiviral vectors. Further identified genes/proteins from stress-treated and silymarin-treated in SKHep1 cell lines with control were validated by RT-PCR, western blot and Immunohistochemistry analysis.
Results: We identified more than 4150 proteins from stress-treated and silymarin-treated in SKhep1 lines with control via LC-MS analysis and focused/target on previously identified eleven key stress-associated proteins, including IPO7, BASP1, SCFD1, TIPRL, SCL25, SERPINB6, TRMT2, and HSP90B1 from Malat1 overexpression cell lines and were validated in leptin, cortisol and Silymarin-treated in SK-Hep1 cells. The Quan ratio and Quan channel values by LC-MS analysis and the Cancer Genome Atlas (TCGA) database analysis confirmed these findings in HCC patient cohorts. Notably, silymarin significantly reduced stress-response gene expression in treated SK-Hep1 cells while sparing untreated parental cells. Further pathway analyses and validation in knockdown models are ongoing to elucidate mechanisms underlying these effects.
Conclusion: Novel therapeutic approach of silymarin as a potential therapeutic agent significantly demonstrated hepatoprotective effects through antioxidant properties. Silymarin effectively downregulated cortisol- and leptin-induced stress-response proteins in SK-Hep1 cells, highlighting its therapeutic potential in stress-associated HCC while developing precision therapy approaches for improved patient outcomes. These findings underscore silymarin's role in targeting novel molecular pathways, offering promising strategies to address HCC disparities in underserved populations in the RGV. This research aims to improve outcomes and reduce mortality among high-risk groups, addressing a critical healthcare challenge in Texas and Worldwide.
Recommended Citation
Hussain, Mohammad Shabir; Anaya, Yamile A.; Sanchez, Amairani; Leslie, Sophia; and Tripathi, Manish Kumar, "Proteomic Profiling of Stress-Associated Proteins in Hepatocellular Carcinoma and The Hepatoprotective Effects of Silymarin" (2025). Research Symposium. 21.
https://scholarworks.utrgv.edu/somrs/2025/talks/21
Included in
Proteomic Profiling of Stress-Associated Proteins in Hepatocellular Carcinoma and The Hepatoprotective Effects of Silymarin
Background: The liver is the principal organ responsible for the detoxification of exogenous and endogenous toxins, xenobiotics, and viruses and bacteria, making it susceptible to damage by various chemicals and metabolites that enter the body. In clinical relevance, Hepatocellular carcinoma (HCC) is a major global health concern, being the sixth most common cancer worldwide and third leading cause of cancer-related death. HCC accounts for 85–90% of liver cancers globally. Texas is projected to have the second-highest liver cancer-related deaths, with Hispanic populations experiencing the highest mortality rates. The liver, a vital metabolic organ, is particularly vulnerable to stress-induced damage. According to the ACS 2024, the USA is expected to report 41,630 new cases and 29,840 deaths from HCC. In the South Texas Rio Grande Valley (RGV), where ~90% of the population is Latino/Hispanic, socioeconomic disparities, poverty, obesity, diabetes, and low-income levels contribute to a high prevalence of stress. Stress exacerbates cancer progression by impairing immune responses, triggering inflammation, and activating the Hypothalamic-Pituitary-Adrenal (HPA) axis, which releases cortisol and leptin, known to influence oncogenesis. These stressors can significantly affect liver function, hastening HCC progression. Critical need for targeted therapies in stress-associated HCC growing importance of natural compounds in cancer treatment, Silymarin as a promising hepatoprotective agent in HCC. The therapeutic Potential of Silymarin, a flavonolignan complex derived from Silybum marianum (milk thistle), has demonstrated hepatoprotective and anticancer properties. Its historical use in liver diseases, such as cirrhosis and hepatitis, underscores its potential as a therapeutic agent in HCC. Studies indicate its antioxidant, anti-inflammatory, and anti-fibrotic properties, which are essential in mitigating stress-induced liver damage.
Methods: Proteins, pathways associated with stress were identified through liquid chromatography-mass spectrometry (LC-MS) and analysis the data by proteome discoverer 2.5 software. HCC cell lines were treated with cortisol and leptin to simulate acute and chronic stress conditions. Gene expression was analyzed via reverse transcription-polymerase chain reaction (RT-PCR), and overexpression models were established using lentiviral vectors. Further identified genes/proteins from stress-treated and silymarin-treated in SKHep1 cell lines with control were validated by RT-PCR, western blot and Immunohistochemistry analysis.
Results: We identified more than 4150 proteins from stress-treated and silymarin-treated in SKhep1 lines with control via LC-MS analysis and focused/target on previously identified eleven key stress-associated proteins, including IPO7, BASP1, SCFD1, TIPRL, SCL25, SERPINB6, TRMT2, and HSP90B1 from Malat1 overexpression cell lines and were validated in leptin, cortisol and Silymarin-treated in SK-Hep1 cells. The Quan ratio and Quan channel values by LC-MS analysis and the Cancer Genome Atlas (TCGA) database analysis confirmed these findings in HCC patient cohorts. Notably, silymarin significantly reduced stress-response gene expression in treated SK-Hep1 cells while sparing untreated parental cells. Further pathway analyses and validation in knockdown models are ongoing to elucidate mechanisms underlying these effects.
Conclusion: Novel therapeutic approach of silymarin as a potential therapeutic agent significantly demonstrated hepatoprotective effects through antioxidant properties. Silymarin effectively downregulated cortisol- and leptin-induced stress-response proteins in SK-Hep1 cells, highlighting its therapeutic potential in stress-associated HCC while developing precision therapy approaches for improved patient outcomes. These findings underscore silymarin's role in targeting novel molecular pathways, offering promising strategies to address HCC disparities in underserved populations in the RGV. This research aims to improve outcomes and reduce mortality among high-risk groups, addressing a critical healthcare challenge in Texas and Worldwide.
