Tanshinone IIA inactivates Akt and induces caspase-dependent death in cervical cancer cells via the mitochondrial pathway

Hu Li,Yan Xu,Lei He,Li Yang

doi:10.3329/bjp.v10i3.23018

Abstract

<p>In human cervical cancer cells pro-apoptotic effect of tanshinone IIA isolated from the ethanol extract of Scutellaria barbata was investigated. Tanshinone IIA treatment resulted in apoptosis and mitochondrial membrane potential loss in the cervical cancer cells. The viability of SW756 and C4-1 cells was reduced in a concentration dependent manner on treatment with tanshinone IIA for 36 hours. Flow cytometric analysis in SW756 cells showed marked increase in accumulation of sub-G1-phase cell population. Tanshinone IIA treatment also caused significant increase in DNA fragmentation in these cells. DAPI staining revealed significant increase in nuclear condensation and apoptotic body formation on tanshinone IIA treatment in SW756 cells However, the effect of tanshinone IIA was reversed by caspase inhibitor, z-VAD-fmk. In tanshinone IIA treated cells Akt phosphorylation was markedly reduced and this decrease was inhibited by LY294002 (phosphatidylinositol-3'-kinase inhibitor). Tanshinone IIA treated apoptotic cells exhibited decrease in expression of Mcl-1. Thus tanshinone IIA induces apoptosis in cervical cancer cells through mitochondrial pathway. </p><p> </p>

Highlights

Cervical cancer is a commonly observed cancer in the females throughout the world with around 290,000 deaths every year (Saslow et al, 2007)
Induction of apoptosis by tanshinone IIA in cervical cancer cells: We used MTT assay to investigate the effect of tanshinone IIA on the viability of SW756 and C4-1 human cervical cells
Our study clearly revealed that tanshinone IIA induced apoptosis in SW756 and C4-1cervical cancer cells

Summary

Introduction

Cervical cancer is a commonly observed cancer in the females throughout the world with around 290,000 deaths every year (Saslow et al, 2007). Contraction of human papillomavirus (HPV) is the major risk inducing factor found in all the cervical cancer patients (Steben and Duarte, 2007). Cervical cancer if detected at the early stage using regular Pap tests makes treatment favorable compared to late stage cancer (Long, 2007; Brinkman et al, 2005). Apoptosis is induced by the activation of enzymes known as caspases which cleave essential proteins producing changes in the morphological characteristics of the cells (Cohen, 1993; White, 1996; Williams and Smith, 1993; Wyllie et al, 1980). Cytochrome c binds to the adaptor protein, Apaf-1 causing its oligomerization and caspase activation (Danial and Korsmeyer, 2004)

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