Title:Triptolide Induces Apoptosis and Autophagy in Cutaneous Squamous Cell Carcinoma
via Akt/mTOR Pathway
Volume: 23
Issue: 13
Author(s): Zhe Zheng, Guorong Yan, Ningyuan Xi, Xiaoxiang Xu, Qingyu Zeng, Yuhao Wu, Ying Zheng*, Guolong Zhang*Xiuli Wang*
Affiliation:
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225009, P.R. China
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225009, P.R. China
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, P.R. China
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225009, P.R. China
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, P.R. China
Keywords:
Triptolide, apoptosis, autophagy, cutaneous squamous cell carcinoma, Akt, mTOR.
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.
