Abstract

Chemotherapy is a general treatment procedure for cancer. The diversity in cancer incidence and the failure of therapy due to chemoresistance lead to increased cancer-related deaths. Therefore, new drugs with fewer secondary complications targeting diverse pathways are the need of the hour. Geranyl isovalerate (GIV), one of the active ingredients of ethyl acetate fraction of Argyreia nervosa is routinely used as a food flavoring agent. In this study, we found that GIV also exhibits anticancer activity when tested against the HCT116 cell line. It influenced the viability of the cells in a dose- and time-dependent manner. We examined whether GIV could induce oxidative stress and affect the mitochondrial membrane potential, thereby leading to apoptosis induction. Moreover, GIV could suppress the expression of antiapoptotic genes, such as BCl2 and PARP, and induce the expression of proapoptotic genes, such as Caspase 3 and 9. This is the first study demonstrating the anticancer activity of GIV and providing evidence for its mechanism of action. In conclusion, this study proposes GIV as a potential lead or supplementary molecule in treating and preventing colorectal cancer (CRC). Based on our findings, we conclude that GIV may be a viable lead or supplementary molecule for treating and preventing CRC.

Highlights

  • Cancer is the second major cause of death worldwide after cardiovascular disease

  • Cytotoxicity of Geranyl isovalerate (GIV) was evaluated against two different Colorectal cancer (CRC) cell lines (HCT116 and HT29) using the MTT assay (Figure 1 and Supplementary Figure S2), which is a calorimetric assay to calculate the metabolic activity of the cell (Stockert et al, 2018)

  • The IC50 value of GIV was found to be around 1.8 mM for HCT116 cells and approximately 4 mM for HT29 cells

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Summary

Introduction

Cancer is the second major cause of death worldwide after cardiovascular disease. The number of deaths due to cancer has been estimated to increase to 14.6 million by 2035. Traditional medicinal herbs are regarded as Geranyl Isovalerate as Cancer Therapeutic one of the major source of pharmacologically active compounds (Fridlender et al, 2015). The importance of biologically active phytochemicals and natural compounds drew the attention of scientists, and it has been reported that in 2014 alone 3,26,000 new natural compounds had been discovered (Banerjee et al, 2015). Out of these 3,26,000 compounds, only around 5% have been found to be effective. Investigation for new drugs targeting diverse pathways plays an important role in the success of cancer chemotherapy

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