Betulinic acid exerts potent antitumor effects on paclitaxel‑resistant human lung carcinoma cells (H460) via G2/M phase cell cycle arrest and induction of mitochondrial apoptosis
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- Published online on: July 6, 2018 https://doi.org/10.3892/ol.2018.9097
- Pages: 3628-3634
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Copyright: © Zhan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
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Abstract
Betulinic acid is a pentacyclic plant compound obtained from the bark of white birch trees and has been demonstrated to exhibit notable pharmacological properties. In the present study, the anticancer potential of betulinic acid on paclitaxel‑resistant lung cancer cell line (H460) was evaluated. Cell viability was evaluated by an MTT assay, and a clonogenic assay was performed to assess the effects on cancer cell colony formation. DAPI staining using fluorescence microscopy and flow cytometry were employed to evaluate the effects of betulinic acid on apoptosis. The effects of betulinic acid on the cell cycle and mitochondrial membrane potential were also evaluated by flow cytometry. The effects of betulinic acid on the protein expression of B‑cell lymphoma‑2 (Bcl‑2)/Bcl‑2‑associated X (Bax) were evaluated by western blot analysis. The results of the present study indicated that the half‑maximal inhibitory concentration value of betulinic acid on paclitaxel‑resistant H460 lung cancer cells was 50 µM. The treatment with betulinic acid was able to inhibit the colony formation potential in a dose‑dependent manner. A lower cytoxicity by betulinic acid against normal human epithelial FR2 cells was observed compared with H460 cells. The betulinic acid exerted anticancer activity via the induction of apoptosis by regulating the Bcl‑2/Bax signaling pathway. Additionally, treatment with betulinic acid resulted in cell cycle arrest of paclitaxel‑resistant lung cancer H460 cells at the G2/M phase. Betulinic acid was also reported to cause reductions in the mitochondrial membrane potential in a dose‑dependent manner. In conclusion, the results of the present study indicated that betulinic acid may be a useful drug candidate for the management of drug‑resistant lung cancer.
