Aloe-Emodin-Mediated Photodynamic Therapy Induces Apoptosis in Basal Cell Carcinoma Cells via Activation of ERK/JNK Signaling Pathway

Woodvine Otieno Odhiambo,Yanhong Ji,Xiaopeng Wang,Xiaodong Chen,Songmei Geng,Farooq Riaz,Mengting Qin,Yang Wang,Meng Yuan,Chengcheng Liu,Alberto Álvarez-Gallegos

doi:10.1155/2021/6935269

Woodvine Otieno Odhiambo, Yanhong Ji + Show 9 more

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https://doi.org/10.1155/2021/6935269

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Abstract

Basal cell carcinoma (BCC) is the most prevalent epidermal cancerous neoplasm. Previous studies have reported the noninvasive, cost-effective, and localized photodynamic therapy (PDT) approach to BCC treatment. This study investigated the photodynamic effects of aloe-emodin (AE), a natural anthraquinone photosensitizer (PS), on proliferation and apoptosis of BCC TE 354.T cell line. To evaluate the effects of AE-mediated PDT, we used various concentrations of AE (0, 2.5, 5, and 10 μM) and white light energy (0, 12, 24, and 36 J/cm2). CCK-8 assay was used to analyse cell viability following AE-mediated PDT. The cell death rate and reactive oxygen species (ROS) were assessed by flow cytometry. Western blotting was used to determine the effects of AE-mediated PDT on the apoptotic proteins, Akt, and MAPK pathways. AE-mediated PDT inhibited tumorigenic cell proliferation, consequently enhancing apoptosis in AE and PDT concentration and dose-dependent manner, respectively. Significantly increased TE 354.T cell apoptosis and intracellular ROS production were both observed after AE-mediated PDT. Following the AE-mediated PDT, cytochrome and antitumor p53 were elevated; however expression of Bcl-2 was significantly decreased. Significant caspase 3 elevation post-AE-mediated PDT suggested intrinsically driven apoptosis. Additionally, AE-mediated PDT significantly suppressed NF-κB, Akt, and ERK pathways while JNK expression was significantly increased. AE-mediated PDT induced TE 354.T cell apoptosis through the intracellular generation of ROS. Akt, ERK, and JNK all play various roles in ensuring successful TE 354.T tumor cell apoptosis.

Highlights

Basal cell carcinoma (BCC) is a slow-growing and locally invasive skin tumor, on the epidermal surface [1, 2]
We investigated two MAPK families (extracellular signal-regulated kinases (ERKs) and C-Jun N-terminal kinases (JNKs)) to understand their involvement during photodynamic therapy (PDT)-mediated apoptosis
This study confirmed that AE in combination with 435 ± 10 nm light is cytotoxic against BCC in an AE concentration and light energy dose-dependent manner

Summary

Introduction

Basal cell carcinoma (BCC) is a slow-growing and locally invasive skin tumor, on the epidermal surface [1, 2]. BCC remains the most prevalent global cancerous neoplasm with an increased incidence in the last decade [3]. Various factors such as closeness to the equator and an aging global population increase the risks and make any race vulnerable, with doubling incidences from 40 to 70 years [4, 5]. BCC may damage the neighbouring tissues and have a relatively high reoccurrence rate in 10-20% of the successfully treated and recovered patients [6]. BCC often occurs on the International Journal of Photoenergy neck, face, or extremities, and cosmetic preference warrants an alternative noninvasive therapeutic mode [6]

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