Mitochondria in colorectal cancer stem cells - a target in drug resistance

Abstract

Colorectal cancer (CRC) is the third most diagnosed cancer and the second most deadly type of cancer worldwide. In late diagnosis, CRC can resist therapy regimens in which cancer stem cells (CSCs) are intimately related. CSCs are a subpopulation of tumor cells responsible for tumor initiation and maintenance, metastasis, and resistance to conventional treatments. In this scenario, colorectal cancer stem cells (CCSCs) are considered an important key for therapeutic failure and resistance. In its turn, mitochondria is an organelle involved in many mechanisms in cancer, including chemoresistance of cytotoxic drugs due to alterations in mitochondrial metabolism, apoptosis, dynamics, and mitophagy. Therefore, it is crucial to understand the mitochondrial role in CCSCs regarding CRC drug resistance. It has been shown that enhanced anti-apoptotic protein expression, mitophagy rate, and addiction to oxidative phosphorylation are the major strategies developed by CCSCs to avoid drug insults. Thus, new mitochondria-targeted drug approaches must be explored to mitigate CRC chemoresistance via the ablation of CCSCs.

Ru(II) Phenanthroline-Based Oligothienyl Complexes as Phototherapy Agents

“…In addition, PDT can induce hypoxia as oxygen is consumed during irradiation. , Decreased generation of ROS limits damage to cancerous cells. To address this, there is motivation to develop light-triggered compounds that exploit oxygen-independent mechanisms for phototoxicity. − In this context, metal complexes such as Ru(II) polypyridyl systems have attracted considerable attention. ,,,− Judicious choice of ligand–metal combinations provides access to a variety of excited-state configurations with characteristic photophysical properties and reactivities. Strategies have included photorelease of bulky ligands to reveal phototoxic metals and/or ligands, ,,,,,− photocaging of chemotherapeutics and enzyme inhibitors, ,,,,,− …”

Mitochondrial fusion–fission dynamics and its involvement in colorectal cancer

“…Research has established that doxorubicin‐ or oxaliplatin‐resistant colon cancer cells exhibit pronounced mitochondrial fragmentation due to increased division [ 40 , 45 ]. Although studies on mitochondrial morphology in the context of drug resistance in CRC stem cells (CCSCs) are lacking, the elevated mitophagy rate implies that mitochondrial fission is a mechanism underlying chemotherapy resistance in CCSCs [ 46 ]. miR‐17‐5p and miR‐27a induce mitochondrial fission, leading to reduced apoptosis and 5‐FU chemoresistance in CRC [ 47 , 48 ].…”

Supramolecular host-guest nanosystems for overcoming cancer drug resistance

“…Mitochondria serves as the center for regulating tumor cell apoptosis [ 131 , 132 ] . Therefore, the destruction of mitochondria is also an effective way to overcome cancer drug resistance [ 133 - 135 ] . Recently, Dai et al synthesized a multivalent supramolecular polymer (HABMitP) by modifying HA with mitochondrial targeting peptide and 4-bromophenylpyridium [ Figure 9A ] [ 136 ] .…”