Guaiazulene Triggers ROS-Induced Apoptosis and Protective Autophagy in Non-small Cell Lung Cancer
1Department of Oncology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Abstract:
Non-small cell lung cancer (NSCLC) is one of the most frequent cancers worldwide, yet effective treatment remains a clinical challenge. Guaiazulene (GYZ), a cosmetic color additive, has previously been characterized as a potential antitumor agent due to observed anticancer effects. However, the efficacy of GYZ in the treatment of NSCLC and the involved molecular mechanisms remain largely unknown. Here, we indicated a role for GYZ in the suppression of NSCLC both in vitro and in vivo via triggering reactive oxygen species (ROS)-induced apoptosis. Concomitantly, GYZ induced complete autophagic flux in NSCLC cells via inhibiting the Akt/mTOR signaling pathway, which displayed cytoprotective effect against GYZ-induced growth suppression. Accompanied with autophagy inhibition obviously enhanced the effects of GYZ. Notably, GYZ acts synergistically with paclitaxel in the suppression of NSCLC in vitro. Together, our results for the first time reported that GYZ suppressed the proliferation of NSCLC and suggested a potential strategy for inhibiting NSCLC growth by combinational use of GYZ and autophagy inhibitors.
Insights
Guaiazulene (GYZ) suppresses non-small cell lung cancer (NSCLC) by inducing apoptosis and autophagy. Combining GYZ with autophagy inhibitors or paclitaxel enhances its anti-NSCLC effects, offering a potential new treatment strategy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Non-small cell lung cancer (NSCLC) presents significant treatment challenges globally.
- Guaiazulene (GYZ), a cosmetic additive, shows potential anticancer properties.
- The specific efficacy and mechanisms of GYZ against NSCLC are not well understood.
Purpose of the Study:
- To investigate the efficacy of Guaiazulene (GYZ) in suppressing non-small cell lung cancer (NSCLC).
- To elucidate the molecular mechanisms underlying GYZ's anti-NSCLC effects.
- To explore the synergistic potential of GYZ in combination with other therapeutic agents.
Main Methods:
- In vitro and in vivo studies were conducted using NSCLC models.
- Reactive oxygen species (ROS) generation and apoptosis induction were assessed.
- Autophagic flux and the Akt/mTOR signaling pathway were analyzed.
- Synergistic effects with paclitaxel and autophagy inhibitors were evaluated.
Main Results:
- Guaiazulene (GYZ) demonstrated significant suppression of NSCLC proliferation both in vitro and in vivo.
- GYZ triggered apoptosis through the induction of reactive oxygen species (ROS).
- GYZ induced complete autophagic flux by inhibiting the Akt/mTOR pathway, which conferred a cytoprotective effect.
- Inhibition of autophagy potentiated GYZ's anti-cancer effects.
- GYZ exhibited synergistic activity with paclitaxel against NSCLC in vitro.
Conclusions:
- Guaiazulene (GYZ) effectively suppresses non-small cell lung cancer (NSCLC) proliferation via ROS-induced apoptosis.
- GYZ-induced autophagy acts as a cytoprotective mechanism in NSCLC.
- Combining GYZ with autophagy inhibitors significantly enhances its therapeutic efficacy against NSCLC.
- GYZ shows synergistic potential with paclitaxel, suggesting a promising therapeutic strategy for NSCLC treatment.
Related Concept Videos
01:31The Intrinsic Apoptotic Pathway
01:18Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...