Pharm Sci. 2021;27(4): 536-542.
doi: 10.34172/PS.2021.12
  Abstract View: 322
  PDF Download: 135

Research Article

The Combination of Berberine and Methotrexate Enhances Anti-Cancer Effects in Hela Cancer Cell Line: A Morphological Study

Hossein Majidzadeh 1,2,3, Mostafa Araj-Khodaei 2, Maryam Ghaffari 4, Amir Jafari 5,6, Dariush Shanehbandi 1, Mohammadali Torbati 2, Jafar Ezzati Nazhad Dolatabadi 7* ORCID logo

1 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Department of Persian Medicine, School of Traditional Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
4 Pharmaceutical Analysis Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
5 Laboratory of Nanoradiopharmaceuticals and Synthesis of Novel Radiopharmaceuticals, Nuclear Engineering Institute, Brazilian Nuclear Energy Commission, Rio de Janeiro, Brazil.
6 Laboratory of Nanoradiopharmacy and Strategic Biomaterials, Zona Oeste State University, Rio de Janeiro, Brazil.
7 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.


Background: Co-administration of two or several either chemotherapeutic agents or conventional drugs as a combination treatment is the most effective method to increase therapeutic efficiency. Additive or synergistic influence are two mechanisms by which combination therapy causes a rise in optimal cancer therapy compared to a single treatment.

Methods: Colorimetric assay was carried out to estimate the cytotoxicity of the combined system, followed by apoptosis assay to calculate the number of apoptotic cells. Both 4′,6-diamidino-2-phenylindole (DAPI) staining and DNA ladder were complemented tests to illuminate morphological changes and DNA fracturing on HeLa cancer cells.

Results: We revealed that the combination of berberine (BER) and methotrexate (MTX) could inhibit the growth of HeLa cancer cells noticeably. Nevertheless, single BER and MTX were not as effective as a combined system to reduce cell viability at the same dose. Regarding the apoptosis induction and change in morphology of cancer cells’ nucleus, co-treatment of BERand MTX was more effective. The result was complemented with flow cytometry, DAPI staining and DNA ladder, which showed that BER+MTX depicted more anti-cancer effects.

Conclusion: The combination therapy of HeLa cancer cells with BER and MTX showed high inhibition effect compared to other treated groups.

Keywords: HeLa cells, Methotrexate, Berberine, Herbal Medicine, Nuclear Morphology
First Name
Last Name
Email Address
Security code

Abstract View: 323

Your browser does not support the canvas element.

PDF Download: 135

Your browser does not support the canvas element.

Submitted: 26 Jan 2021
Revision: 27 Feb 2021
Accepted: 27 Feb 2021
ePublished: 03 Mar 2021
EndNote EndNote

(Enw Format - Win & Mac)

BibTeX BibTeX

(Bib Format - Win & Mac)

Bookends Bookends

(Ris Format - Mac only)

EasyBib EasyBib

(Ris Format - Win & Mac)

Medlars Medlars

(Txt Format - Win & Mac)

Mendeley Web Mendeley Web
Mendeley Mendeley

(Ris Format - Win & Mac)

Papers Papers

(Ris Format - Win & Mac)

ProCite ProCite

(Ris Format - Win & Mac)

Reference Manager Reference Manager

(Ris Format - Win only)

Refworks Refworks

(Refworks Format - Win & Mac)

Zotero Zotero

(Ris Format - Firefox Plugin)