Abstract

Rhaponticum carthamoides (Willd.) Iljin. is an endemic plant species, which is important in Siberian medicine. It possesses adaptogenic properties and has been used for treatment of overstrain and weakness after illness, physical weakness, and mental weariness. The roots of this species obtained after Agrobacterium rhizogenes transformation are rich in caffeoylquinic acid derivatives known as strong antioxidant compounds. The study makes the first evaluation of the cytotoxic and genotoxic activity of transformed root extract (Rc TR extract) in various human cancer cell lines: leukemia cells (K-562 and CCRF-CEM) and lung adenocarcinoma cells (A549). It was found that Rc TR extract inhibited the cell viability of all tested cell lines in a concentration-dependent manner, and leukemia cell lines were more sensitive to plant extract than A549 lung cancer cell line. Additionally, the Rc TR extract reduced the mitochondrial membrane potential and demonstrated genotoxicity against tested cell lines by increasing mitochondrial DNA lesions in ND1 and ND5 genes and causing nuclear DNA damage in TP53 gene. Our results show that Rc TR extract may effectively treat cancer cells by inducing dysfunction of mitochondria. Additionally, the role of mtDNA may be a promising factor in chemotherapy, and it needs further studies.

Highlights

  • The plant antioxidant compounds have long been known to have beneficial effects on human health; recent studies indicate that they may cause apoptosis and death of cancer cells [1]

  • In reference to our earlier studies regarding the cytotoxicity of R. carthamoides transformed root extract against human glioma cells, the aim of the present study is estimate its cytotoxic and genotoxic activities in two human leukemia cell lines: myeloid (K-562) and lymphoid (CCRF-CEM) and lung cancer cell line (A549) by evaluating cell viability, mitochondrial DNA and nuclear DNA damages, loss of mitochondrial membrane potential, and alteration of mtDNA copy number

  • Three human cancer cell lines were used in this study: K-562 chronic myelogenous leukemia, CCRF-CEM leukemic lymphoblasts, and A549 lung adenocarcinoma

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Summary

Introduction

The plant antioxidant compounds have long been known to have beneficial effects on human health; recent studies indicate that they may cause apoptosis and death of cancer cells [1]. Rhaponticum carthamoides (Willd.) Iljin (Asteraceae) is an endemic plant species whose roots and rhizomes have been used for many years in traditional Siberian medicine These raw materials are a component in nutraceutical preparations and diet supplements and are used as adaptogenic and anabolic preparations. In recent years, researchers have sought potential alternatives in obtaining plant material and valuable compounds with therapeutic effect. One such method is plant biotechnology based on in vitro cultures, especially transformed root cultures; these are characterized by high metabolite content and biomass production in a short time. The transformed roots of R. carthamoides demonstrated enhanced production of tricaffeoylquinic acid derivatives compared to the normal roots of soil-grown plants, and they offer an attractive alternative to conventional cultivation and obtainment of the valuable secondary metabolites

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