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Updated: Aug 12, 2025
Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
Published on: May 14, 2016
An AIE luminogen targeting the endoplasmic reticulum inhibits cancer cell growth via multicellular organelle
Li Yang1, Xing Wang1, Yongfei Zhao1
1School of Chemistry and Chemical Engineering, Southeast University, Nanjing, Jiangsu 211189, PR China.
Abstract:
Organelle-targeted photodynamic therapy has been increasingly investigated in recent decades, but little attention has been paid to the damage caused to other non-primary target organelles during the course of action, even though these non-primary target organelles may play a substantial role in inhibiting the growth of cancer cells. In this contribution, we report an AIE-type strong endoplasmic reticulum-targeted luminogen (MTOQS) with a distorted structure, which is efficient in producing ROS both in cellular and non-cellular environment, causing an effective reduction of high levels of GSH and MDA in cancer cells through the efficient accumulation of intracellular ROS, and the levels of ATP, l-lactic acid, anti-apoptotic factor Bcl-2 and apoptotic protein caspase-3 were determined. Through the identification of these markers, it was evidenced that MTOQS-induced dual organelle oxidative stress could diminish the degree of oxidative phosphorylation and glycolysis in cancer cells and trigger an alteration in the culture environment of cancer cells, while causing damage to the endoplasmic reticulum and mitochondria through multiorganelle oxidative stress, turning on the pathway of apoptosis and consequently driving cancer cells to apoptosis.
Insights
This study introduces MTOQS, a novel endoplasmic reticulum-targeting agent that generates reactive oxygen species (ROS). MTOQS effectively reduces cancer cell growth by inducing oxidative stress in multiple organelles, triggering apoptosis.
Area of Science:
- Biochemistry
- Cell Biology
- Materials Science
Background:
- Organelle-targeted photodynamic therapy is under investigation for cancer treatment.
- Damage to non-target organelles during therapy is often overlooked but crucial for efficacy.
Purpose of the Study:
- To develop and evaluate an aggregation-induced emission (AIE) luminogen (MTOQS) for endoplasmic reticulum targeting.
- To investigate the effects of MTOQS-induced oxidative stress on cancer cell metabolism and apoptosis.
Main Methods:
- Synthesis of a distorted AIE luminogen (MTOQS) with endoplasmic reticulum affinity.
- Measurement of reactive oxygen species (ROS) production in cellular and non-cellular environments.
- Quantification of glutathione (GSH), malondialdehyde (MDA), ATP, lactate, Bcl-2, and caspase-3 levels in cancer cells.
Main Results:
- MTOQS efficiently produces ROS, reducing GSH and MDA levels in cancer cells.
- MTOQS accumulation leads to diminished oxidative phosphorylation and glycolysis.
- MTOQS induces multi-organelle oxidative stress, damaging endoplasmic reticulum and mitochondria, activating apoptosis.
Conclusions:
- MTOQS demonstrates potential as an endoplasmic reticulum-targeted agent for cancer therapy.
- Dual organelle oxidative stress induced by MTOQS effectively triggers apoptosis in cancer cells.
- Targeting multiple organelles offers a promising strategy for enhancing photodynamic therapy efficacy.
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