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11 April 2020 : Laboratory Research  

Lung Cancer Inhibition by Betulinic Acid Nanoparticles via Adenosine 5’-Triphosphate (ATP)-Binding Cassette Transporter G1 Gene Downregulation

Hao Zhao1BCD, Xiaoyan Mu2BCD, Xiaopeng Zhang3CDE, Qingyong You1ACDEF*

DOI: 10.12659/MSM.922092

Med Sci Monit 2020; 26:e922092

Abstract

BACKGROUND: Despite scientific advancement in radiotherapy and chemotherapy, the 5-year survival rate of lung cancer patients is around 15%. The present study explored the anticancer potential of betulinic acid nanoparticles against lung cancer cells.

MATERIAL AND METHODS: The proliferative changes in lung cancer cells by betulinic acid nanoparticles were measured by MTT assay. Cell cycle analysis was performed by flow cytometry using propidium iodide stain. Transwell and wound healing assay were used for determination of HKULC2 cell metastatic potential.

RESULTS: The betulinic acid nanoparticle treatment significantly (P<0.05) reduced proliferation of HKULC2, H1299, and H23 cells. The proliferation of HKULC2, H1299, and H23 cells was reduced to 33%, 28% and 24%, respectively on treatment with 10 µM of betulinic acid nanoparticles. The results from flow cytometry showed that betulinic acid nanoparticle exposure lead to cell cycle arrest in G1 phase in HKULC2 cells. Treatment with betulinic acid nanoparticles markedly decreased migration potential of HKULC2 cells. The invasive ability of HKULC2 cells was also suppressed markedly on exposure to betulinic acid nanoparticles. Western blotting of HKULC2 cells showed that betulinic acid nanoparticles promoted the expression of p21 and p53 and downregulated CD133, ALDH, BCL2, MCL1, and c-Myc expression. Betulinic acid nanoparticles reduced the expression of ABCG1 protein markedly.

CONCLUSIONS: The present study demonstrated that betulinic acid nanoparticles inhibit proliferation, metastatic ability, and arrest cell cycle in lung cancer cells through downregulation of ABCG1 oncogene expression. Therefore, betulinic acid nanoparticles may be used as therapeutic agent for the treatment of lung cancer.

Keywords: Apoptosis, Chemoembolization, Therapeutic, Neoplasm Recurrence, Local, ATP Binding Cassette Transporter, Subfamily G, Member 1, Antineoplastic Agents, Phytogenic, Cell Cycle Checkpoints, Cell Proliferation, Down-Regulation, Gene Expression Regulation, Neoplastic, Lung Neoplasms, Nanoparticles, Pentacyclic Triterpenes, Triterpenes

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750