Withania somnifera Root Extract Enhances Chemotherapy through ‘Priming’

Withania somnifera extracts are known for their anti-cancerous, anti-inflammatory and antioxidative properties. One of their mechanisms of actions is to modulate mitochondrial function through increasing oxidative stress. Recently ‘priming’ has been suggested as a potential mechanism for enhancing cancer cell death. In this study we demonstrate that ‘priming’, in HT-29 colon cells, with W. somnifera root extract increased the potency of the chemotherapeutic agent cisplatin. We have also showed the W. somnifera root extract enhanced mitochondrial dysfunction and that the underlying mechanism of ‘priming’ was selectively through increased ROS. Moreover, we showed that this effect was not seen in non-cancerous cells

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Assessing cell viability of <i>W</i>. <i>somnifera</i> root extract on cancer and non-cancer cells.

<p>Cells were treated with increasing concentrations (1 μg/mL <i>-</i>10 μg/mL) of <i>W</i>. <i>somnifera</i> root extract for 48 h in <b>(A)</b> MDA-MB231, <b>(B)</b> HT-29 and <b>(C)</b> MCF10A cells. Data represent the average of 5 independent experiments ± SEM. *p<0.05, **p<0.01 <i>vs</i> non-treatment (0).</p

Mitochondrial functional analysis following 48 h of <i>W</i>. <i>somnifera</i> root extract treatment in MDA-MB231, HT-29 and MCF10A cells.

<p>Mitochondrial function was assessed using a Seahorse Bioanalyser following 48 h of 1 μg/mL and 10 μg/mL <i>W</i>. <i>somnifera</i> root extract treatment. Alterations in MDA-MB231 cancer cells <b>(A)</b> basal respiration, <b>(B)</b> ATP production, <b>(C)</b> proton leak and <b>(D)</b> maximal respiration was investigated following treatment. The same functional alterations were observed in HT-29 cells (E–H) and in MCF10A cells (I-L). Data represents the average of 3 independent experiments ± SEM. *p<0.05, ** p<0.01, *** p<0.001 <i>vs</i> non-treatment.</p

The effect of ‘priming’ with <i>W</i>. <i>somnifera</i> root extract prior to cisplatin treatment on cell viability.

<p>Cell viability was assessed following ‘priming’ with <i>W</i>. <i>somnifera</i> root extract (1 μg/mL, 5 μg/mL and 10 μg/mL) for 48 h prior to 100 μM cisplatin treatment. <b>(A)</b> MDA-MB231, <b>(B)</b> HT-29 and <b>(C)</b> MCF10A cell viability following ‘priming’ with <i>W</i>. <i>somnifera</i> root extract and 100 μM cisplatin treatment alone. Data represents the average of 5 independent experiments ± SEM. *p<0.05, ** p<0.01, *** p<0.001 <i>vs</i> non-treatment, # p<0.05, ### p<0.001 <i>vs</i> cisplatin.</p

Oxidative stress alteration following treatment with <i>W</i>. <i>somnifera</i> in cancer and non-cancer cells.

<p>ROS levels were measured using a DCFDA assay following 48 h treatment with 1 μg/mL, 5 μg/mL and 10 μg/mL of <i>W</i>. <i>somnifera</i> root extract in <b>(A)</b> MDA-MB231, <b>(B)</b> HT-29 and <b>(C)</b> MCF10A cells. The bold line in each graph represents control treatment levels for the experiment. Data represent the average of 5 independent experiments ± SEM. *p<0.05 <i>vs</i> non-treatment.</p

Oxidative stress response following ‘priming’ with <i>W</i>. <i>somnifera</i> root extract.

<p>The alteration to oxidative stress levels was assessed following ‘priming’ with <i>W</i>. <i>somnifera</i> from 1 μg/mL to 10 μg/mL 48 h prior to 100 μM cisplatin treatment in <b>(A)</b> MDA-MB231, <b>(B)</b> HT-29 and <b>(C)</b> MCF10A cells. The bold line in each graph represents control treatment levels for the experiment Data represents the average of 5 independent experiments ± SEM. *p<0.05, **p<0.01, ***p<0.001 <i>vs</i> non-treatment, # p<0.05, ## p<0.01, ### p<0.001 <i>vs</i> cisplatin.</p