In Vitro Study of the Cytotoxic, Cytostatic, and Antigenotoxic Profile of Hemidesmus indicus (L.) R.Br. (Apocynaceae) Crude Drug Extract on T Lymphoblastic Cells.

Eleonora Turrini,Carmela Fimognari,Giulia Greco,Alessandra Guerrini,Guglielmo Paganetto,Thomas Efferth,Gianni Sacchetti,Cinzia Calcabrini,Massimo Tacchini,Elena Catanzaro

doi:10.3390/toxins10020070

Eleonora Turrini, Carmela Fimognari + Show 8 more

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https://doi.org/10.3390/toxins10020070

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Abstract

In traditional Indian medicine, the crude drug Hemidesmus indicus root—commonly known as Indian sarsaparilla—is used alone or in poly-herbal preparations for the treatment of a wide range of diseases. The present study focuses on the cancer chemopreventive and therapeutic potential of H. indicus extracts on an acute lymphoblastic leukemia cell line (CCRF-CEM). With this aim in mind, we subjected H. indicus roots to two subsequent extractions (hydro-alcoholic extraction and soxhlet extraction). As DNA damage is an important prerequisite for the induction of mutations/cancer by genotoxic carcinogens, cancer chemoprevention may be achieved by preventing genotoxicity. Through an integrated experimental approach, we explored the genoprotective potential of the soxhlet H. indicus extract against different mutagenic compounds and its cytotoxic, proapoptotic, and cytostatic properties. In our experimental conditions, H. indicus induced a cytotoxic effect involving the activation of both intrinsic and extrinsic apoptotic pathways and blocked the cell cycle in the S phase. Moreover, the antigenotoxicity results showed that the extract was able to mitigate DNA damage, an essential mechanism for its applicability as a chemopreventive agent, via either the modulation of extracellular and intracellular events involved in DNA damage. These data add to the growing body of evidence that H. indicus can represent a noteworthy strategy to target early and late stages of cancer.

Highlights

From ancient times to recent times, natural products have always represented a keystone in medicine
It is clear that the complexity of natural products is the key of their powerful activity
Our results suggest that H. of indicus evokes an inhibition of cell proliferation supported by a cell type-dependent modulation a different phase of the cell cycle

Summary

Introduction

From ancient times to recent times, natural products have always represented a keystone in medicine. Natural products store within them numerous molecules, all potentially pharmacologically active, which together can affect more than one biological pathway, resulting in a wide global activity [1]. In this context, the potentiality of natural drugs to treat a complex pathology as cancer is enormous. Carcinogenesis is a multistep process characterized by subsequent phases that foresees the transformation of normal cells into neoplastic ones [2]. This process starts with the acquisition of DNA mutations in different key genes (oncogenes), named the initiation phase. The World Health Organization indicated the prevention of breast cancer as a factual, therapeutic approach [3,4]

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