# Methyl linolenate suppresses the growth and proliferation of Ehrlich ascites carcinoma (EAC) cells by inducing intrinsic mitochondrial apoptosis

## TL;DR

Methyl linolenate, a compound from Clerodendrum viscosum, inhibits cancer cell growth and extends survival in mice by triggering mitochondrial apoptosis.

## Contribution

Methyl linolenate is a novel anticancer compound that induces apoptosis and inhibits angiogenesis in EAC cells.

## Key findings

- ML inhibited EAC cell growth by 67% at 3.0 mg/kg/day and increased survival time in mice.
- ML treatment upregulated pro-apoptotic genes and downregulated anti-apoptotic genes in EAC cells.
- ML reduced tumor weight, cell volume, and angiogenesis in EAC-bearing mice.

## Abstract

A new bioactive compound, methyl linolenate (Methyl-octadeca-9,12,15-trienote), designated as ML, was isolated and purified from Clerodendrum viscosum leaves. Treatment of Ehrlich ascites carcinoma (EAC) cells with ML induced cancer growth inhibition dose-dependently, with a maximum cell growth inhibition of 67 % at a dose of 3.0 mg/kg/day (p<0.001). It also inhibits EAC cell volume and tumor weight and increases the survival time of EAC-bearing mice (25 versus 41 days) (p<0.001). In addition, EAC-bearing control mice exhibited a drastic deterioration of blood parameters, and treatment of EAC-bearing mice with ML prevented the deterioration of hematological parameters compared to untreated EAC-bearing mice. Also, ML abrogates angiogenesis by inhibiting the development of new blood vessels in the peritoneum of EAC-bearing mice. ML-treated cells exhibited apoptotic features such as condensed, fragmented nuclear material and cell membrane damage. Expression of pro-apoptotic genes such as p53, Bax, Caspase 3, and Caspase 9 was upregulated, whereas anti-apoptotic gene Bcl2 was downregulated in ML-treated EAC cells, which indicates the induction of intrinsic mitochondrial apoptosis of EAC cells. However, as it is a novel anticancer compound showing an antineoplastic effect, inhibiting angiogenesis, and inducing apoptosis in mouse models, thus, using other cellular models and more preclinical and clinical research is essential for further development.

See also the graphical abstract(Fig. 1).