Adv Pharm Bull. 2020;10(3): 472-476.
doi: 10.34172/apb.2020.058
  Abstract View: 60
  PDF Download: 48

Short Communication

Kaempferol-Mediated Sensitization Enhances Chemotherapeutic Efficacy of Sorafenib Against Hepatocellular Carcinoma: An in Silico and in Vitro Approach

Bhagyalakshmi Nair 1 ORCID logo, Ruby John Anto 2, Sabitha M 1, Lekshmi R. Nath 1 * ORCID logo

1 Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara P.O., Kochi, Kerala 682041, India.
2 Division of Cancer Research, Rajiv Gandhi Center for Biotechnology, Thycaud, Thiruvananthapuram, Kerala- 695014, India. Introduction


Purpose: Sorafenib is the sole FDA approved drug conventionally used for the treatment ofadvanced hepatocellular carcinoma (HCC). Despite of the beneficial use of sorafenib in thetreatment of HCC, multidrug resistance still remains a challenge. HCC is inherently known aschemotherapy resistant tumor due to P-glycoprotein (P-gp)-mediated multidrug resistance.Methods: We studied the interaction energy of kaempferol with human multidrug resistanceprotein-1 (RCSB PDB ID: 2CBZ) using in silico method with the help of BIOVIA DiscoveryStudio. HepG2 and N1S1 liver cancer cell lines were treated in suitable cell culture media toevaluate the efficacy of kaempferol in chemo-sensitizing liver cancer cells towards the effect ofsorafenib. Cell viability study was performed by MTT assay.Results: In silico analysis of kaempferol showed best docking score of 23.14 with Human MultiDrug Resistant Protein-1 (RCSB PDB ID: 2CBZ) compared with positive control verapamil. Inin-vitro condition, combination of sub-toxic concentrations of both kaempferol and sorafenibproduced 50% cytotoxicity with concentration of 2.5 μM each which indicates that kaempferolhas the ability to reverse the MDR by decreasing the over-expression of P-gp.Conclusion: Kaempferol is able to sensitize the HepG2 and N1S1 against the sub-toxicconcentration of sorafenib. Hence, we consider that the efficacy of sorafenib chemotherapy canbe enhanced by the significant approach of combining the sub-toxic concentrations of sorafenibwith kaempferol. Thus, kaempferol can be used as a better candidate molecule along withsorafenib for enhancing its efficacy, if validated through preclinical studies.
Keywords: Hepatocellular carcinoma, Sorafenib, Kaempferol, Multi-drug resistance, Combination therapy, P-gp inhibitors
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Submitted: 29 Oct 2019
Revision: 02 Feb 2020
Accepted: 03 Feb 2020
ePublished: 11 May 2020
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