Curcumin in combination with homoharringtonine suppresses lymphoma cell growth by inhibiting the TGF-β/Smad3 signaling pathway

• Published in: Aging (Albany, NY.) NY.), 2021-07, Vol.13 (14), p.18757-18768
• Main Authors: Zhang, Yu, Xiang, Jingjing, Zhu, Ni, Ge, Hangping, Sheng, Xianfu, Deng, Shu, Chen, Junfa, Yu, Lihong, Zhou, Yan, Shen, Jianping
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; bcl-2-Associated X Protein - metabolism; Cadherins - metabolism; Caspase 3 - metabolism; Caspase 9 - metabolism; Cell Line, Tumor; Cell Proliferation; Cephalotaxus - chemistry; Curcuma - chemistry; Curcumin - pharmacology; Curcumin - therapeutic use; Drug Therapy, Combination; Homoharringtonine - pharmacology; Homoharringtonine - therapeutic use; Lymphoma - drug therapy; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Phytotherapy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Research Paper; Signal Transduction; Smad3 Protein - metabolism; Transforming Growth Factor beta - metabolism; Xenograft Model Antitumor Assays
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.203319

Both homoharringtonine (HHT) and curcumin exhibit anti-proliferative effects on lymphoma cells, but the effects of combined HHT and curcumin treatment remain unclear. Here, we investigated the effects of HHT/curcumin combination on the proliferation, apoptosis, and invasion in lymphoma cells. CCK-8, flow cytometry, and transwell assays were used to assess proliferation, apoptosis, and invasion of U937 and Raji cells. p-Smad3, E-cadherin, and N-cadherin expression were also measured in Raji cells using Western blot assays. Combination of HHT and curcumin synergistically inhibited U937 and Raji cell proliferation and invasion. In addition, the combination treatment markedly increased apoptosis of Raji cells as evidenced by increased Bax, cleaved caspase 3, and cleaved caspase 9 expression. Meanwhile, the combination treatment promoted anti-tumor mechanisms in Raji cells as indicated by decreases in p-Smad3 and N-cadherin and increases in E-cadherin. experiments showed that the combination treatment suppressed tumor growth in a mouse Raji xenograft model. Our findings indicate that combination of HHT and curcumin inhibited lymphoma cell growth by downregulating the TGF-β/Smad3 pathway. These results suggest that HHT combined with curcumin might be a promising therapeutic approach for the treatment of lymphoma.