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INTERNATIONAL CONGRESS OF

CancerGenetics

• Exploring Natural Flavonoids as Potential Inhibitors of ABC Transporters in Human Renal Cell Carcinoma

• Mohamad Vosough Ghanbari,¹ Zahra Nasiri Sarvi,² Fatemeh Behnam Rassouli,^3,*
  1. Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  2. Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
  3. Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
  
  
  
• Introduction: Renal cell carcinoma (RCC) is a significant global health concern, ranking as the sixth most frequently diagnosed cancer in males and the tenth in females worldwide. The increasing incidence of RCC, with an annual rise of approximately 2%, underscores the urgent need for innovative therapeutic strategies to combat this malignancy. Drug resistance in RCC poses a substantial obstacle to effective treatment, The objective of present study was to determine whether natural flavonoids Hesperetin, Luteolin and Ampelopsin have the potential to target drug resistance mediators, ABCB1 and ABCC1.
• Methods: The analysis of ABCB1 and ABCC1 expression in RCC was conducted via GEPIA2 web-tool, which uses RNA sequencing data from the cancer genome atlas. The SMILE codes of natural flavonoids were retrieved from PubChem database, and then subjected to SwissTargetPrediction to predict the most probable protein targets of our bioactive small molecules.
• Results: Gene expression analysis revealed significant (p<0.01) up-regulation of ABCB1 in RCC patients (286 samples) in comparison with normal tissues (60 samples). Elevated expression of ABCC1 was also detected in RCC samples, although not significant (p>0.05). Investigating the probability of Hesperetin to target ABCB1 and ABCC1 was as 0.111 and 0.127, respectively. Regarding Luteolin, probability was as 0.534 and 0.658 for ABCB1 and ABCC1, respectively. In addition, the predicted probability of Ampelopsin to target both ABCB1 and ABCC1 was as 0.109.
• Conclusion: According to the current computational analysis, Luteolin has the highest probability to target ABC transporters, and thus, could be considered as a potent small molecule to combat drug resistance in RCC.
• Keywords: Renal cell carcinoma, Drug resistance, ABC transporters, Natural flavonoids, Luteolin.