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Updated: May 10, 2026
Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel
Published on: May 14, 2018
Differential effects of paclitaxel and docetaxel on gap junctions affects their cytotoxicities in transfected HeLa
Nan Tang1, Qin Wang, Dengpan Wu
1Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
Abstract:
Gap junctions (GJs) enhance the cytotoxicity of specific cancer chemotherapeutic drugs and therefore, the inhibition of functional GJs may represent a mechanism by which the toxicity of chemotherapeutics in cancer cells can be reduced. In the present study, the effects and mechanisms of paclitaxel and docetaxel on GJ intercellular communication (GJIC) and the modulation of drug cytotoxicity were investigated in HeLa cells that were stably transfected with the connexin (Cx) 32 expression plasmid. Paclitaxel, but not docetaxel, was observed to inhibit dye‑coupling through junctional channels. Gating closure rather than the alteration of Cx32 expression or its membrane localization was responsible for the inhibitory action of paclitaxel on GJ function following short‑term exposure. The results revealed that the cytotoxicity of paclitaxel or docetaxel increased in the presence of functional GJs compared with that observed when GJIC was suppressed. In addition, paclitaxel‑induced downregulation of GJIC decreased the cytotoxicity of paclitaxel in the presence of functional GJs compared with that of docetaxel, which did not affect Cx32 channels. These observations demonstrated that the differential effects of paclitaxel and docetaxel on GJIC may affect the cytotoxicity of chemotherapeutic drugs. The present study provides a promising new approach to select antineoplastics and improve drug efficacy in carcinoma cells that form GJs.
Insights
Inhibiting gap junctions (GJs) can reduce chemotherapy toxicity. Paclitaxel, but not docetaxel, inhibits GJs, altering drug efficacy in cancer cells expressing connexin 32.
Area of Science:
- Cell Biology
- Pharmacology
- Cancer Research
Background:
- Gap junctions (GJs) facilitate intercellular communication.
- Functional GJs can enhance the cytotoxicity of certain chemotherapeutic drugs.
- Inhibiting GJs may offer a strategy to reduce chemotherapy side effects.
Purpose of the Study:
- Investigate the effects of paclitaxel and docetaxel on GJ intercellular communication (GJIC).
- Determine how these drugs modulate GJIC and their cytotoxicity in HeLa cells.
- Explore the role of connexin 32 (Cx32) in these interactions.
Main Methods:
- Utilized HeLa cells stably transfected with a Cx32 expression plasmid.
- Assessed paclitaxel and docetaxel effects on dye-coupling and GJIC.
- Evaluated drug cytotoxicity under conditions of suppressed versus functional GJIC.
Main Results:
- Paclitaxel inhibited dye-coupling via Cx32 channels through gating closure, not altered expression or localization.
- Docetaxel did not significantly affect Cx32 channels or GJIC.
- Drug cytotoxicity was higher with functional GJs; paclitaxel's GJIC inhibition reduced its own cytotoxicity.
Conclusions:
- Differential effects of paclitaxel and docetaxel on GJIC influence their cytotoxicity.
- Targeting GJIC offers a novel approach for selecting and improving chemotherapeutic efficacy in GJ-forming carcinomas.
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