The Effectiveness of the Nimali Variety of Sri Lankan Punica granatum L. Fruit Extracts on Rhabdomyosarcoma (RD) Cells Concerning the Apoptotic Signaling Pathway.

Udeshika Bandara,Preethi Soysa,Chamindri Witharana

doi:10.31557/apjcp.2022.23.2.501

Udeshika Bandara, Preethi Soysa + Show 1 more

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https://doi.org/10.31557/apjcp.2022.23.2.501

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Abstract

Objective: Pomegranate ,a polyphenol-rich fruit, has been considered as one of the ancient fruits with anticancer effect. Cell cycle arrest is considered as an ordinary factor in human cancer, and apoptosis is the frequent drug target. This study aimed to evaluate the effectiveness of the Nimali variety of Sri Lankan Punica granatum L. fruit extracts on rhabdomyosarcoma (RD) cells concerning the apoptotic signaling pathway. Methods: Antiproliferative activity of aqueous extracts of pomegranate peel, pericarp, was assessed using multiple extraction methods (sonication, microwaving, sonication followed by microwaving, keeping in a waterbath, and boiling at 100ºC). Total protein content, nitric oxide production, LDH, and caspase-8 and caspase-3 activities were analyzed in peel extracts prepared by sonicated or microwave methods. RT-qPCR was performed with intact RNA to explore the apoptotic pathway and gene expression. Results:Peel extracts expressed minimum cell viability in a dose-dependent manner, induced cell death on RD cells. However, sonicated peel extract (SPL) indicated the lowest IC50 of 14.8±2.2 μg/mL comparative to healthy VERO cells (>1,000 μg/mL). A decrease of nitrite content in the supernatant was visualized in the graph plotted against concentration. Furthermore, SPL upregulated caspase-8 and caspase-3 signaling pathways and expression of p21 and p53 genes. Conclusion:The findings highlighted the promising therapeutic potential of SPL to inhibit RD growth and progression and to modulate the caspase-8 and caspase-3, p53, and p21 dependent pathway.

Highlights

World Health Organization has reported cancer as the second cause of mortality with 9.6 million deaths in 2018
Pomegranate fruit is rich in potent antioxidants, tannins, and phenolics
Pomegranate peel comprises of polyphenols and constitutes about 50% of the total fruit weight, it is discarded as waste

Summary

Introduction

World Health Organization has reported cancer as the second cause of mortality with 9.6 million deaths in 2018. 70% of deaths from cancer are reported in low and middle-income countries (WHO, 2018). Phytochemicals are currently practiced as a treatment for cancers. Pomegranate has been considered as a polyphenol-rich ancient fruit and belongs to Lythraceae family. It can cure a wide range of diseases in folk and ayurvedic medicine. Studies have reported that pomegranate peel, pericarp, juice, seeds, leaves, and bark have antioxidant properties providing numerous health benefits (Amar et al, 2017). Ellagic acid exhibits a wide spectrum of antitumor properties through multiple pathways (Zhang et al, 2014). Masci et al, (2016) concluded that polyphenols were susceptible to oxidative degradation extraction conditions can considerably affect the efficiency, stability, and yield of polyphenols differing antioxidant activity in pomegranate fruit extracts

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