Kaempferol-Mediated Sensitization Enhances Chemotherapeutic Efficacy of Sorafenib Against Hepatocellular Carcinoma: An In Silico and In Vitro Approach, Short Communication

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Nair Bhagyalakshmi; Anto Ruby John; M. Sabitha; Nath Lekshmi R.

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Journal: Advanced Pharmaceutical Bulletin Year:2020 | Volume:10 | Issue:3 Page(s): 472-476

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Title

Kaempferol-Mediated Sensitization Enhances Chemotherapeutic Efficacy of Sorafenib Against Hepatocellular Carcinoma: An In Silico and In Vitro Approach, Short Communication

Author(s)

Nair Bhagyalakshmi | Anto Ruby John | M. Sabitha | Nath Lekshmi R. | Issue Writer Certificate

Keywords

Hepatocellular carcinoma

Sorafenib

Kaempferol

Multi-drug resistance

Combination therapy

P-gp inhibitors

Abstract

Purpose: Sorafenib is the sole FDA approved drug conventionally used for the treatment of advanced Hepatocellular carcinoma (HCC). Despite of the beneficial use of Sorafenib in the treatment of HCC, multidrug resistance still remains a challenge. HCC is inherently known as chemotherapy resistant tumor due to P-glycoprotein (P-gp)-mediated multidrug resistance. Methods: We studied the interaction energy of Kaempferol with human multidrug resistance protein-1 (RCSB PDB ID: 2CBZ) using in silico method with the help of BIOVIA Discovery Studio. HepG2 and N1S1 liver cancer cell lines were treated in suitable cell culture media to evaluate the efficacy of Kaempferol in chemo-sensitizing liver cancer cells towards the effect of Sorafenib. Cell viability study was performed by MTT assay. Results: In silico analysis of Kaempferol showed best docking score of 23. 14 with Human Multi Drug Resistant Protein-1 (RCSB PDB ID: 2CBZ) compared with positive control verapamil. In in-vitro condition, combination of sub-toxic concentrations of both Kaempferol and Sorafenib produced 50% cytotoxicity with concentration of 2. 5 μ M each which indicates that Kaempferol has 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-toxic concentration of Sorafenib. Hence, we consider that the efficacy of Sorafenib chemotherapy can be enhanced by the significant approach of combining the sub-toxic concentrations of Sorafenib with Kaempferol. Thus, Kaempferol can be used as a better candidate molecule along with Sorafenib for enhancing its efficacy, if validated through preclinical studies.

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APA: Copy

Nair, Bhagyalakshmi, Anto, Ruby John, M., Sabitha, & Nath, Lekshmi R.. (2020). Kaempferol-Mediated Sensitization Enhances Chemotherapeutic Efficacy of Sorafenib Against Hepatocellular Carcinoma: An In Silico and In Vitro Approach, Short Communication. ADVANCED PHARMACEUTICAL BULLETIN, 10(3), 472-476. SID. https://sid.ir/paper/741495/en

Vancouver: Copy

Nair Bhagyalakshmi, Anto Ruby John, M. Sabitha, Nath Lekshmi R.. Kaempferol-Mediated Sensitization Enhances Chemotherapeutic Efficacy of Sorafenib Against Hepatocellular Carcinoma: An In Silico and In Vitro Approach, Short Communication. ADVANCED PHARMACEUTICAL BULLETIN[Internet]. 2020;10(3):472-476. Available from: https://sid.ir/paper/741495/en

IEEE: Copy

Bhagyalakshmi Nair, Ruby John Anto, Sabitha M., and Lekshmi R. Nath, “Kaempferol-Mediated Sensitization Enhances Chemotherapeutic Efficacy of Sorafenib Against Hepatocellular Carcinoma: An In Silico and In Vitro Approach, Short Communication,” ADVANCED PHARMACEUTICAL BULLETIN, vol. 10, no. 3, pp. 472–476, 2020, [Online]. Available: https://sid.ir/paper/741495/en

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