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SDIRSACR Oncology Insights

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Dual targeting concept: hybrid molecules of cisplatin and antiinflammatory drugs

Dijana Bovan 1

1 Department of Immunology, Institute for Biological Research “Siniša Stanković”, National Institute of the Republic of Serbia,
University of Belgrade, Belgrade; Serbia

Keywords: antiinflammatory drugs, chemotherapy, drug delivery, platinum

Background: Recently, it has become evident that dying cells play a central role in promoting cell division and serve as a
primary source of signals driving tumor repopulation and the development of an aggressive phenotype. Prostaglandin
E2 (PGE2), a proinflammatory molecule, has a prominent role in delivering a mitogenic signal to neighboring cells,
thus providing a therapeutic opportunity against cancer. With an aim to block mitogenic signal of PGE2, we created
hybrid molecules composed of nonsteroidal antiinflammatory drugs and conventional platinum-based cytostatic. This
multitargeting approach enables induction of cell death without tumor repopulation feedback. In addition to official
cyclooxygenase 2 (COX-2) inhibitors, many unexplored plant metabolites, for instance alkyl esters of caffeic acid (CA),
demonstrate significant enzyme inhibition. To further improve antitumor potential of novel compounds, mesoporous
nanosilica was employed as drug delivery vehicle. In this study Pt(IV) complexes based on cisplatin scaffold bearing
naproxen, ibuprofen, flurbiprofen, and derivative of CA, loaded into silica SBA-15 were evaluated in 2D and 3D cell
culture as well as in vivo syngeneic mouse model of melanoma, breast and colon cancer.
Material and Methods: The cytotoxicity of four conjugates on 4T1, B16, CT26, and MC38 cell lines was estimated
by MTT and CV assays. Organoids were established from MC38-induced tumors in C57BL/6 mice which were then
isolated, digested and further propagated. CellTiter-Glo™ luminescent assay was employed for evaluation of the drugs'
effect on organoids. In vivo efficacy was investigated in tumor-challenged C57BL/6 and BALB/c mice. Flow cytometry
and microscopy were employed in order to enlight the mechanism of action of selected conjugates.
Results: All tested hybrid drugs significantly reduced viability of cell lines in 2D cultures with high reproducibility in
3D cultures. In mouse model of melanoma, breast and colon cancer, tumor shrinkage and a better toxicity profile
comparing to cisplatin were noticeable. Mechanistic insight on melanoma in vitro has indicated a pro-senescent action
of selected drugs.
Conclusions: This strategy of combining cytotoxic drug and antiinflammatory agents holds great potential for developing
treatment options that simultaneously target cancer cells and intercellular network in tumor microenvironment.

Acknowledgments and funding:Thanks to the Ministry of Science, Technological Development, and Innovation of the
Republic of Serbia (No. 451-03-136/2025-03/200007) and the Science Fund of the Republic of Serbia, Prisma Program,
# GRANT No 5456, Project – ADVANCED for financial support.

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Acrylamide in Food and Its Carcinogenic Potential: What Do We Really Know?

Aysegül ÇEBİ1

1Giresun University, Faculty of Health Sciences, Giresun, Türkiye

Keywords: acrylamide, carcinogen, food

Acrylamide, a chemical compound formed in carbohydrate-rich foods during high-temperature cooking processes such
as frying, baking, and roasting, has been classified as a probable human carcinogen based on animal studies. These
studies have demonstrated that acrylamide and its metabolite, glycidamide, can cause DNA damage and increase cancer
risk in rodents. Acrylamide has been demonstrated to exert deleterious effects in experimental animals. Evidence has
emerged that this substance is toxic to certain tissues, including reproductive tissues and the retina. In addition, studies
have indicated that it is neurotoxic to rats and mice. The substance undergoes conversion to glycidamide, a highly
reactive epoxide, by CYP2E in humans. This process results in the acquisition of genotoxic and carcinogenic properties

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