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Cancer and Immunology

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Biomedical Science

Abstract

Background: Pancreatic cancer (PanCa) is the fourth deadliest cancer worldwide and expected to become the second deadliest cancer by 2030. In the USA, the National Cancer Institute put forth a grim prediction stating that there will be 64,050 new cases in 2023 alone and about 50,000 of these patients will die. The first line treatment for pancreatic cancer is Folfrinox, a three-drug regimen consisting of 5-Fluorouracil, irinotecan, and oxaliplatin. The second line treatment is gemcitabine combined with paclitaxel. Only 19% of patients who are prescribed the former regimen survive past 18 months of treatment while just 6% of patients survive past 18 months with gemcitabine. In addition to these regimens, the overall five-year survival rate for pancreatic cancer patients only stands at 11%. Therefore, the discovery of potentially new molecular targets is warranted. In pancreatic cancer, the ribosome biogenesis is dysregulated because the tumor cells require an increased amount of protein synthesis. Furthermore, RPA194, a catalytic subunit of RNA Polymerase I, is overexpressed to meet this demand by elevating the number of ribosomes. Apoptotic pathways are also downregulated to enhance the survivability of PanCa.

Methods: The cytotoxicity of honey was determined in four PanCa cell lines i.e., AsPc-1, MiaPaCa-2, Capan-2, and HPAF-2, using MTT assay. Western blotting was done to assess the regulatory role of honey on distinct proteins involved in ribosome biogenesis, nuclear stress, and apoptosis. Polymerase Chain Reaction (PCR) was utilized to determine the expression of genes within these cancer cells. Confocal microscopy was used to detect proteins associated with ribosome biogenesis and nuclear stress. Cell cycle analysis was performed to assess cellular arrest in specific stage of the cell cycle. The percentage of cells that underwent programmed cellular death was measured by apoptosis assay.

Results: MTT analysis indicated that honey exerted dose-dependent cellular cytotoxicity in AsPc- 1, MiaPaCa-2, Capan-2, and HPAF-2 cells, four pancreatic cancer cell lines. The western blotting analysis revealed that the treatment with honey markedly targeted the process of ribosome biogenesis via downregulating the expression of RPA-194 (catalytic unit of RNA Pol), RPA-135, RPL-29, c-Myc, nucleolin (NCL), and fibrillarin (FBL) in AsPC-1 and MiaPaCa-2 cells. The mRNA expression analysis also indicated the effect of honey on ribosome biogenesis in PanCa cells. The same findings were further validated through confocal microscopy. Cell cycle analysis indicated a concentration-dependent decrease of cancer cells in the G1 stage and a concentration-dependent G2/M phase arrest in AsPc-1 and MiaPaCa-2 cells. Apoptosis assay indicated early and late-stage apoptosis in cancer cells with honey administration. Furthermore,honey also induced the apoptosis in AsPC-1 and MiaPaCa-2 cells via targeting p53 (truncated and mutated, respectively), Bcl-2 (important for apoptosis), cleaved PARP, and Caspase-3 expression.

Conclusions: Honey, as a natural compound, can serve as an anticancer agent via targeting both ribosome biogenesis and apoptotic pathways. Honey has the potential to become a therapeutic of interest for future patients due to its medicinal effects, natural properties, and attractive prices. However, more studies are warranted to understand the complex and diverse mechanisms that honey utilizes in combating pancreatic cancer.

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Poster

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Honey: A Natural Recipe for the Management of Pancreatic Cancer

Background: Pancreatic cancer (PanCa) is the fourth deadliest cancer worldwide and expected to become the second deadliest cancer by 2030. In the USA, the National Cancer Institute put forth a grim prediction stating that there will be 64,050 new cases in 2023 alone and about 50,000 of these patients will die. The first line treatment for pancreatic cancer is Folfrinox, a three-drug regimen consisting of 5-Fluorouracil, irinotecan, and oxaliplatin. The second line treatment is gemcitabine combined with paclitaxel. Only 19% of patients who are prescribed the former regimen survive past 18 months of treatment while just 6% of patients survive past 18 months with gemcitabine. In addition to these regimens, the overall five-year survival rate for pancreatic cancer patients only stands at 11%. Therefore, the discovery of potentially new molecular targets is warranted. In pancreatic cancer, the ribosome biogenesis is dysregulated because the tumor cells require an increased amount of protein synthesis. Furthermore, RPA194, a catalytic subunit of RNA Polymerase I, is overexpressed to meet this demand by elevating the number of ribosomes. Apoptotic pathways are also downregulated to enhance the survivability of PanCa.

Methods: The cytotoxicity of honey was determined in four PanCa cell lines i.e., AsPc-1, MiaPaCa-2, Capan-2, and HPAF-2, using MTT assay. Western blotting was done to assess the regulatory role of honey on distinct proteins involved in ribosome biogenesis, nuclear stress, and apoptosis. Polymerase Chain Reaction (PCR) was utilized to determine the expression of genes within these cancer cells. Confocal microscopy was used to detect proteins associated with ribosome biogenesis and nuclear stress. Cell cycle analysis was performed to assess cellular arrest in specific stage of the cell cycle. The percentage of cells that underwent programmed cellular death was measured by apoptosis assay.

Results: MTT analysis indicated that honey exerted dose-dependent cellular cytotoxicity in AsPc- 1, MiaPaCa-2, Capan-2, and HPAF-2 cells, four pancreatic cancer cell lines. The western blotting analysis revealed that the treatment with honey markedly targeted the process of ribosome biogenesis via downregulating the expression of RPA-194 (catalytic unit of RNA Pol), RPA-135, RPL-29, c-Myc, nucleolin (NCL), and fibrillarin (FBL) in AsPC-1 and MiaPaCa-2 cells. The mRNA expression analysis also indicated the effect of honey on ribosome biogenesis in PanCa cells. The same findings were further validated through confocal microscopy. Cell cycle analysis indicated a concentration-dependent decrease of cancer cells in the G1 stage and a concentration-dependent G2/M phase arrest in AsPc-1 and MiaPaCa-2 cells. Apoptosis assay indicated early and late-stage apoptosis in cancer cells with honey administration. Furthermore,honey also induced the apoptosis in AsPC-1 and MiaPaCa-2 cells via targeting p53 (truncated and mutated, respectively), Bcl-2 (important for apoptosis), cleaved PARP, and Caspase-3 expression.

Conclusions: Honey, as a natural compound, can serve as an anticancer agent via targeting both ribosome biogenesis and apoptotic pathways. Honey has the potential to become a therapeutic of interest for future patients due to its medicinal effects, natural properties, and attractive prices. However, more studies are warranted to understand the complex and diverse mechanisms that honey utilizes in combating pancreatic cancer.

 

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