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Triptolide Induces Apoptosis and Autophagy in Cutaneous Squamous Cell Carcinoma via Akt/mTOR Pathway

Zhe Zheng^1,2, Guorong Yan^1,2, Ningyuan Xi²

¹Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225009, P.R. China.

Anti-Cancer Agents in Medicinal Chemistry

|April 14, 2023

Abstract

Background:

Tripterygium wilfordii Hook F provided the source of the first diterpenoid triepoxide lactone, Triptolide, identified as the primary constituent causing the anticancer activity. So far, it has not been reported whether triptolide has a therapeutic effect on cutaneous squamous cell carcinoma (cSCC).

Objective:

This study investigates the triptolide's therapeutic impact on cSCC both in vitro and in vivo and investigates the triptolide's potential involvement in signaling pathways.

Methods:

The CCK-8 assays, wound healing assays, and colony formation assays were used to assess the effects of triptolide on the proliferation and migration of cSCC cells. The alteration in gene expression following triptolide treatment was shown by RNA sequencing. Flow cytometry was then applied to evaluate cell apoptosis. Western blot was used to find the associated proteins' expressions. The effectiveness of triptolide was then evaluated in vivo using a xenograft model, and histological staining was employed to determine the visceral toxicity.

Results:

Triptolide greatly reduces the migratory and proliferative capacity of cSCC cells. Triptolide dramatically decreased cell viability and migration in the A431 and SCL-1 cells compared to the control group, according to the CCK8 assay, wound healing assay, and colony formation assay. Flow cytometry demonstrated that treatment with 10- 40 nM triptolide increased apoptosis in a concentration-dependent manner, with a statistically significant difference. Furthermore, mice given triptolide had smaller tumor sizes than those in the control group. Triptolide treatment drastically altered the expression of autophagic and apoptotic proteins. The considerable reduction in the proteins Akt and mTOR levels further illustrated the critical function of triptolide in cSCC.

Conclusion:

Triptolide caused cSCC cells to engage in autophagy and apoptosis by inhibiting the Akt/mTOR signaling pathways. Triptolide may be a possible antitumor agent for the treatment of cSCC.

Insights

Triptolide, derived from Tripterygium wilfordii, effectively inhibits cutaneous squamous cell carcinoma (cSCC) growth by inducing apoptosis and autophagy. This natural compound shows promise as an anticancer agent for cSCC treatment.

Area of Science:

Pharmacology
Oncology
Molecular Biology

Background:

Triptolide, a diterpenoid triepoxide lactone from Tripterygium wilfordii, exhibits anticancer properties.
The therapeutic potential of triptolide for cutaneous squamous cell carcinoma (cSCC) remains largely unexplored.

Purpose of the Study:

To investigate the therapeutic effects of triptolide on cSCC in vitro and in vivo.
To elucidate the role of triptolide in cSCC signaling pathways.

Main Methods:

Cell viability, proliferation, and migration assays (CCK-8, wound healing, colony formation).
RNA sequencing for gene expression analysis.
Flow cytometry for apoptosis assessment.
Western blotting for protein expression analysis.
In vivo xenograft model and histological examination for efficacy and toxicity.

Main Results:

Triptolide significantly reduced cSCC cell viability, proliferation, and migration.
Concentration-dependent induction of apoptosis was observed.
Tumor growth was suppressed in vivo.
Triptolide altered autophagic and apoptotic protein expression, notably reducing Akt and mTOR levels.

Conclusions:

Triptolide induces autophagy and apoptosis in cSCC cells by inhibiting the Akt/mTOR signaling pathway.
Triptolide demonstrates potential as an antitumor agent for cSCC treatment.

Read full analysis

Keywords:

Akt Triptolide apoptosis autophagy cutaneous squamous cell carcinoma mTOR

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