The Anti-Cancer Effect of Four Curcumin Analogues on Human Glioma Cells

Siou-Min Luo; Yi-Ping Wu; Li-Chun Huang; Shih-Ming Huang; Dueng-Yuan Hueng

doi:10.2147/OTT.S313961

The Anti-Cancer Effect of Four Curcumin Analogues on Human Glioma Cells

Onco Targets Ther. 2021 Aug 4:14:4345-4359. doi: 10.2147/OTT.S313961. eCollection 2021.

Authors

Siou-Min Luo¹, Yi-Ping Wu², Li-Chun Huang², Shih-Ming Huang^{1

2}, Dueng-Yuan Hueng^{1

2

3}

Affiliations

¹ Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
² Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, Republic of China.
³ Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.

Abstract

Purpose: Glioblastoma multiforme (GBM) is the primary aggressive malignancy of the brain with poor outcome. Curcumin analogues are polyphenolic compounds as the bioactive substances extracted from turmeric. This study aims to investigate the anti-cancer effects of four curcumin analogues. Furthermore, the molecular mechanisms of dimethoxycurcumin in human gliomas were analyzed by Western blot.

Materials and methods: Human LN229 and GBM8401 glioma cells were treated by four curcumin analogues with different number of methoxy groups. The cell viability, cell cycle, apoptosis, proliferation and ROS production of human gliomas were analyzed by flow cytometry. Moreover, the effects of four curcumin analogues on tumorigenesis of gliomas were conducted by wound healing assay and colony formation assay. Furthermore, the molecular mechanisms of dimethoxycurcumin in human gliomas were analyzed by Western blot.

Results: Our data showed that four different curcumin analogues including curcumin, bisdemethoxycurcumin, demethoxycurcumin, and dimethoxycurcumin promote sub-G1 phase, G2/M arrest, apoptosis, and ROS production in human glioma cells. Moreover, dimethoxycurcumin suppressed cell viability, migration, and colony formation, induction of sub-G1, G2/M arrest, apoptosis, and ROS production in glioma cells. Moreover, the mechanism of dimethoxycurcumin is ROS production to increase LC3B-II expression to induce autophagy. Furthermore, dimethoxycurcumin suppressed apoptotic marker, BCL-2 to promote apoptosis in LN229 and GBM8401 glioma cells.

Conclusion: Our study found that dimethoxycurcumin induced apoptosis, autophagy, ROS production and suppressed cell viability in human gliomas. Dimethoxycurcumin might be a potential therapeutic candidate in human glioma cells.

Keywords: bisdemethoxycurcumin; curcumin; demethoxycurcumin; dimethoxycurcumin; glioblastoma.

Grants and funding

This work was supported, in part, by grants from the Ministry of Science and Technology (MOST 106-2314-B-016-012-MY3, and MOST 108-2314-B-016-026 -MY3 to D.-Y.H.), Tri-Service General Hospital (TSGH-C107- 008-S05, ATSGH-C107-008-S05, TSGH-C108-007-008-S05, TSGH-C01-109016, TSGH-1-C108-106-2314-B-016-012-MY3, and TSGH-C05-110034 to D.-Y.H), and Medical Affairs Bureau, Ministry of National Defense (MAB-106-019, MAB-107-009, MAB-108-022, MAB-109-014, and MAB-110-115 to D.-Y.H).