SP-8356: A Novel Verbenone Derivative Exerts In Vitro Anti-Non-Small Cell Lung Cancer Effects, Promotes Apoptosis via The P53/MDM2 Axis and Inhibits Tumor Formation in Mice

Document Type : Original Article

Authors

Department of Clinical Laboratory, People’s Hospital of Chongqing Liang jiang New Area, Chongqing, China

Abstract

Objective: Non-small cell lung cancer (NSCLC) stands as a prominent contributor to cancer-related fatalities on a
global scale, necessitating the search for novel therapeutic agents. SP-8356, a derivative of (1S)-(–)-verbenone, has
shown promise as an anticancer agent in preclinical studies. However, specific mechanisms underlying its effects in
NSCLC remain to be elucidated. The aim of this research was to explore the in vitro anti-NSCLC effects of SP-8356,
elucidate its mechanisms of action, and assess its efficacy in inhibiting tumor formation in a murine model.
Materials and Methods: In this experimental study, NSCLC cell lines were treated with various concentrations of SP-
8356. Cell viability and proliferation were assessed using MTT and colony formation assays, respectively. Cell cycle
distribution was analyzed by flow cytometry, and apoptosis was evaluated by determining apoptotic protein expression.
Western blot analysis was conducted to assess protein expression levels of the both p53 and MDM2. Additionally, we
evaluated efficacy of the SP-8356 in inhibiting tumor formation of the nude mouse model.
Results: SP-8356 demonstrated a concentration-dependent inhibition of cell proliferation in the NSCLC cell lines. Flow
cytometric analysis showed that SP-8356 led to cell cycle arrest at the G2/M phase, indicating its potential influence
on regulating the cell cycle. SP-8356 treatment was associated with the downregulation of CDK1 and Cyclin B1.
Additionally, SP-8356 significantly enhanced apoptosis in NSCLC cells. SP-8356 treatment was associated with the
downregulation of Bcl-2, while Bax expression was upregulated. Mechanistically, SP-8356 led to accumulation of the
p53 protein levels within the NSCLC cells. This accumulation was mediated through inhibition of its negative regulator,
MDM2. Using a nude mouse model demonstrated that SP-8356 effectively inhibited tumor formation in vivo.
Conclusion: Our findings shed light on the molecular mechanisms underlying anticancer activity of SP-8356 and
highlight its potential as a promising therapeutic candidate for NSCLC treatment.

Keywords

Main Subjects

References

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Cell Journal (Yakhteh)
Volume 25, Issue 12 - Serial Number 119
December 2023
Pages 839-846

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