Abstract

Renal cell carcinoma (RCC) is the most common kidney cancer leading to 140,000 deaths per year. Among all RCCs 80% evolve from the epithelial proximal tubular cells within the kidney. There is a high tendency of developing chemoresistance and resistance to radiation therapy in most RCC patients. Therefore, kidney resection is considered as the most effective treatments for patients having localized RCC. There is a high tendency of post-operative recurrence among 20–40% of the patients and this recurrence is not curable. It is also clear that modern medicine has no curative treatment options against metastatic RCC. Lupeol [lup-20(29)-en-3β-ol] is a pentacyclic triterpenoid compound naturally found in various edible fruits and in many traditionally used medicinal plants, and has been demonstrated as effective against highly metastatic melanoma and prostate cancers. The present study was designed to evaluate the effect of lupeol to RCC with molecular details. Treatment with lupeol on SK-RC-45 (a RCC cell line) with the LC50 dose of 40μM (for 48 h) induces mitochondrial hyper fission which eventually leads to apoptosis while SK-RC-45 counteracts by enhancing autophagy-mediated selective removal of fragmented mitochondria. This is the first study which concurrently reports the effects of lupeol on RCC and its effect on the mitochondrial dynamics of a cell. Herein, we conclude that lupeol has potential to be an effective agent against RCC with the modulation of mitochondrial dynamics.

Highlights

  • Renal cell carcinoma (RCC) is the most common kidney cancer with over 350,000 cases reported annually, causing 140,000 deaths per year [1]

  • We have established that (1) the administration of Lupeol significantly reduces the viability of RCC cell SK-RC-45; (2) it alters the mitochondrial dynamics by inducing mitochondrial fission which sequentially leads to apoptosis; (3) cell alienates the process by inducing autophagy response probably with an aim to remove fragmented mitochondrial copies

  • In this study we have found that Lupeol have profound effect on the viability of the RCC cell, SK-RC-45 (Fig. 1)

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Summary

Introduction

Renal cell carcinoma (RCC) is the most common kidney cancer with over 350,000 cases reported annually, causing 140,000 deaths per year [1]. This cancer is reported to be the third leading cause of death for urological tumors [2]. Kidney resection is considered to be the most effective treatments for patients having localized RCC [3]. For this study we have investigated the effects of lupeol (Fig. 1a) on a RCC cell line, SK-RC-45 We have selected this particular cell line because these cells were generated from a human kidney cancer in the lining of the proximal convoluted tubule (PCT), the most common RCC [9]

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