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Pharmaceutics
Volume 17
Issue 2
10.3390/pharmaceutics17020158
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Synergistic Anti-Cancer Activities of Curcumin Derivative CU17 Combined with Gemcitabine Against A549 Non-Small-Cell Lung Cancer Cells

by
Narissara Namwan
1,
Gulsiri Senawong
1,
Chanokbhorn Phaosiri
2,
Pakit Kumboonma
3,
La-or Somsakeesit
4,
Arunta Samankul
1,
Chadaporn Leerat
1 and
Thanaset Senawong
1,*
1
Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand
2
Department of Chemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand
3
Department of Applied Chemistry, Faculty of Science and Liberal Arts, Rajamangala University of Technology Isan, Nakhon Ratchasima 30000, Thailand
4
Department of Chemistry, Faculty of Engineering, Rajamangala University of Technology Isan, Khon Kaen 40000, Thailand
*
Author to whom correspondence should be addressed.
Pharmaceutics 2025, 17(2), 158; https://doi.org/10.3390/pharmaceutics17020158
Submission received: 4 January 2025 / Revised: 17 January 2025 / Accepted: 21 January 2025 / Published: 24 January 2025
Versions Notes

Abstract

Recently, the curcumin derivative CU17 possessing HDAC inhibitory activity has been shown to synergistically enhance the anti-proliferative activity of Gem against lung cancer cells. Nevertheless, the mechanism(s) underlying the synergistic anti-cancer effect remains to be investigated. This study aimed to investigate the mechanisms that underpin the anti-cancer activity of the combined Gem and CU17 against NSCLC A549 cells both in vitro and in mouse xenograft models. CU17 was successfully synthesized and subsequently investigated for its combination effects with Gem on inductions of cell cycle arrest and apoptosis in A549 cells. The combination treatment substantially decreased cell survival through S phase prolongation and G2/M phase cell cycle arrest via up-regulating the expressions of p21 and p53 proteins. Additionally, CU17 potentiated the apoptotic effect of Gem in A549 cells by increasing the Bax/Bcl-2 ratio. The co-treatment resulted in an up-regulation of pERK1/2 and Ac-H3 expression. An in vivo study demonstrated that CU17 significantly improved the anti-cancer effect of Gem in nude mice utilizing A549 cell xenografts. The hematoxylin and eosin (H&E) staining results indicated that CU17 decreased the toxicity of Gem to the liver, kidneys, and spleen. Overall, CU17 enhanced the effectiveness of Gem while decreasing its toxicity. This compound shows promise as a chemosensitizer for NSCLC treatment with Gem.
Keywords: lung cancer; gemcitabine; curcumin derivative CU17; drug combination; cell cycle arrest; apoptosis; HDAC inhibitor; chemosensitizer lung cancer; gemcitabine; curcumin derivative CU17; drug combination; cell cycle arrest; apoptosis; HDAC inhibitor; chemosensitizer

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MDPI and ACS Style

Namwan, N.; Senawong, G.; Phaosiri, C.; Kumboonma, P.; Somsakeesit, L.-o.; Samankul, A.; Leerat, C.; Senawong, T. Synergistic Anti-Cancer Activities of Curcumin Derivative CU17 Combined with Gemcitabine Against A549 Non-Small-Cell Lung Cancer Cells. Pharmaceutics 2025, 17, 158. https://doi.org/10.3390/pharmaceutics17020158

AMA Style

Namwan N, Senawong G, Phaosiri C, Kumboonma P, Somsakeesit L-o, Samankul A, Leerat C, Senawong T. Synergistic Anti-Cancer Activities of Curcumin Derivative CU17 Combined with Gemcitabine Against A549 Non-Small-Cell Lung Cancer Cells. Pharmaceutics. 2025; 17(2):158. https://doi.org/10.3390/pharmaceutics17020158

Chicago/Turabian Style

Namwan, Narissara, Gulsiri Senawong, Chanokbhorn Phaosiri, Pakit Kumboonma, La-or Somsakeesit, Arunta Samankul, Chadaporn Leerat, and Thanaset Senawong. 2025. "Synergistic Anti-Cancer Activities of Curcumin Derivative CU17 Combined with Gemcitabine Against A549 Non-Small-Cell Lung Cancer Cells" Pharmaceutics 17, no. 2: 158. https://doi.org/10.3390/pharmaceutics17020158

APA Style

Namwan, N., Senawong, G., Phaosiri, C., Kumboonma, P., Somsakeesit, L.-o., Samankul, A., Leerat, C., & Senawong, T. (2025). Synergistic Anti-Cancer Activities of Curcumin Derivative CU17 Combined with Gemcitabine Against A549 Non-Small-Cell Lung Cancer Cells. Pharmaceutics, 17(2), 158. https://doi.org/10.3390/pharmaceutics17020158

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