Para-Phenylenediamine Induces Apoptotic Death of Melanoma Cells and Reduces Melanoma Tumour Growth in Mice.

Debajit Bhowmick,Rajarshi Chakrabarti,Nabanita Chatterjee,Tuhin Subhra Sarkar,Krishna Das Saha,Subhadip Das,Anirban Siddhanta,Kaushik Bhar,Sanjaya K Mallick

doi:10.1155/2016/3137010

Abstract

Melanoma is one of the most aggressive forms of cancer, usually resistant to standard chemotherapeutics. Despite a huge number of clinical trials, any success to find a chemotherapeutic agent that can effectively destroy melanoma is yet to be achieved. Para-phenylenediamine (p-PD) in the hair dyes is reported to purely serve as an external dyeing agent. Very little is known about whether p-PD has any effect on the melanin producing cells. We have demonstrated p-PD mediated apoptotic death of both human and mouse melanoma cells in vitro. Mouse melanoma tumour growth was also arrested by the apoptotic activity of intraperitoneal administration of p-PD with almost no side effects. This apoptosis is shown to occur primarily via loss of mitochondrial membrane potential (MMP), generation of reactive oxygen species (ROS), and caspase 8 activation. p-PD mediated apoptosis was also confirmed by the increase in sub-G0/G1 cell number. Thus, our experimental observation suggests that p-PD can be a potential less expensive candidate to be developed as a chemotherapeutic agent for melanoma.

Highlights

Melanoma is one of the most notorious types of cancer known to us
Biochemistry Research International time, we have demonstrated that p-PD causes disruption of mitochondrial membrane potential and generation of reactive oxygen species (ROS) leading to apoptosis of these cells primarily via activation of caspase 8
While the inhibitor of caspase 9 showed no protection in p-PD induced cell death, the PAN inhibitor of caspases significantly prevented cell death induced by higher dosage of p-PD in particular. This protective effect of caspase 8 inhibitor on apoptosis was verified by flow cytometry experiments where the numbers of Annexin V positive cells in response to pPD (24 hours) were reduced by 37 and 73% for early and late apoptosis, respectively, when pretreated with caspase 8 inhibitor as compared to the “no inhibitor” set. These results demonstrate that a large extent of p-PD induced apoptotic death of melanoma cells is mediated by the activation of caspase 8

Summary

Introduction

Melanoma is one of the most notorious types of cancer known to us. Studies indicate that melanoma is resistant to most types of chemotherapy by exploiting their intrinsic apoptosis resistance and by reprogramming the proliferative pathways during melanoma development [1,2,3]. Recent studies show that melanoma cells have the ability to delay apoptotic death [4]. Para-phenylenediamine (p-PD) has long been known to be an essential component of permanent hair dyes [5]. P-PD has been used in textile, leather, and hair dye industries [6]. P-PD in the hair dyes is reported to purely serve as an external dyeing agent [5]. Sporadic side effects in human and in mouse model of p-PD are reported [7,8,9,10]

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