Cyclometallated phenylpyridyl Iridium complexes as potential anticancer agents in cervical cancer via connexin-43 mediated Gap Junction Intercellular Communication Loss

Pani, Soumili (2023) Cyclometallated phenylpyridyl Iridium complexes as potential anticancer agents in cervical cancer via connexin-43 mediated Gap Junction Intercellular Communication Loss. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS dissertation of Soumili Pani (18MS097)) Thesis_18MS097.pdf - Submitted Version Restricted to Repository staff only Download (4MB)

Abstract

Researchers worldwide have been focused on creating an effective anticancer treatment with minimal side effects. Currently authorized medications such as cisplatin, oxaloplatin, and carboplatin have low cytotoxicity and selectivity towards cancer cells, so researchers have been exploring other transition metal-based scaffolds. Iridium-based complexes have shown promise as anticancer agents due to their ability to exhibit variable oxidation states and kinetic stability in biological systems , high water solubility, promising anti-proliferative activity in vitro and in vivo. These complexes have diverse mechanisms of action, such as interference with cellular redox balance, interactions with protein kinases, and regulation of non-apoptotic pathways in addition to generation of reactive oxygen species, which induce cell apoptosis by acting on mitochondria and DNA. Additionally, iridium complexes can serve as bio-imaging and bio-sensing agents due to their good photo-stability and cell permeability. They can inhibit cell growth through DNA interactions and act as efficient photo synthesizers and catalysts. Iridium complexes can interact and bind with proteins through hydrophobic interactions, causing a loss of function. Gap junction intercellular communication (GJIC) plays a crucial role in maintaining tissue homeostasis and regulating cell growth and differentiation. Connexin 43 is a type of gap junction protein that has been studied for its role in protecting cells against oxidative stress-induced cell death. The role of Connexin 43 in tumor growth and progression is complex and can be both pro-tumoral and anti-tumoral. It has been shown that gap junctional intercellular communication (GJIC) is reduced in cancer cells compared to their normal counterparts. In some types of cancer, decreased connexin expression and loss of GJIC is associated with cancer onset and progression. GJIC disruption in cancer cells causes uncontrolled cell proliferation, reduced apoptosis, and increased invasiveness. Recent studies suggest that restoring GJIC in cancer cells may inhibit tumour growth and promote cell death, making it a potential treatment. In certain other types of cancer, re-expression of connexins and intense GJIC are associated with a high invasive potential and metastatic capability of cancer cells. To understand whether iridium complexes can be used as potential anticancer agents by targeting the connexin proteins, docking studies, immunofluorescence and western blot was done to assess the binding potential of the complexes.

Actions (login required)

View Item