PMID- 33857585 OWN - NLM STAT- MEDLINE DCOM- 20210617 LR - 20220531 IS - 1873-3476 (Electronic) IS - 0378-5173 (Linking) VI - 601 DP - 2021 May 15 TI - Anti-proliferative and apoptotic effect of gemini curcumin in p53-wild type and p53-mutant colorectal cancer cell lines. PG - 120592 LID - S0378-5173(21)00397-5 [pii] LID - 10.1016/j.ijpharm.2021.120592 [doi] AB - Despite recent advances in therapy, colorectal cancer remains a leading cause of death in affected people. Curcumin is the main bioactive compound of turmeric that has been demonstrated as an effective agent against cancer. However, its poor stability and bioavailability limit therapeutic application. We previously showed that delivery of curcumin by using gemini surfactant nanoparticles called gemini curcumin (Gemini-Cur) could improve its solubility, uptake and toxic effect on breast and ovarian cancer cells. Here, we aimed to investigate the anticancer activity of Gemini-Cur in both p53-mutant and p53-wild type colorectal cancer cells. The toxicity of Gemini-Cur on HT-29 and HCT116 was studied through MTT, uptake kinetics, fluorescence microscopy, annexin V/FITC, and cell cycle assays. Also, real-time PCR and western blotting were performed to evaluate the expression of p53, p21, BAX, BCL-2, and NOXA genes. Our data showed that Gemini-Cur not only enters cells quite rapidly compared to free curcumin crystals, but also suppresses HT-29 and HCT-116 cells proliferation in a time- and dose-dependent manner (p < 0.001). The IC50 values as well as apoptosis assays showed that p53-wild type cells are sensitive to Gemini-Cur. Flow cytometry also revealed that the number of apoptotic cells is dramatically increased in HCT-116 cells earlier than HT-29 cells (p < 0.0001). Gemini-Cur upregulated apoptotic genes including p53 (in both mutant and wild-type forms), p21, NOXA and BAX while decreased anti-apoptotic BCL-2 in mRNA and protein level (p < 0.0001). As a hallmark of apoptosis, the expression ratio of BAX/BCL-2 was significantly increased in all treated cells. Taken together, our findings demonstrated that Gemini-Cur suppresses the proliferation of cancer cells via induction of apoptosis and could be considered as novel nano-formulated phytochemical for cancer targeting. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Ebrahimi, Masoumeh AU - Ebrahimi M AD - Department of Animal Biology, School of Natural Sciences, University of Tabriz, Tabriz, Iran. FAU - Babaei, Esmaeil AU - Babaei E AD - Department of Animal Biology, School of Natural Sciences, University of Tabriz, Tabriz, Iran; Institute of Environment, University of Tabriz, Tabriz, Iran. Electronic address: babaei@tabrizu.ac.ir. FAU - Neri, Francesco AU - Neri F AD - Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany. FAU - Feizi, Mohammad Ali Hosseinpour AU - Feizi MAH AD - Department of Animal Biology, School of Natural Sciences, University of Tabriz, Tabriz, Iran. LA - eng PT - Journal Article DEP - 20210420 PL - Netherlands TA - Int J Pharm JT - International journal of pharmaceutics JID - 7804127 RN - 0 (Antineoplastic Agents) RN - 0 (TP53 protein, human) RN - 0 (Tumor Suppressor Protein p53) RN - IT942ZTH98 (Curcumin) SB - IM MH - *Antineoplastic Agents/pharmacology MH - Apoptosis MH - Cell Line, Tumor MH - *Colorectal Neoplasms/drug therapy/genetics MH - *Curcumin/pharmacology MH - HCT116 Cells MH - Humans MH - Tumor Suppressor Protein p53/genetics OTO - NOTNLM OT - Apoptosis OT - Colon cancer OT - Gemini curcumin OT - p53 Mutant EDAT- 2021/04/16 06:00 MHDA- 2021/06/22 06:00 CRDT- 2021/04/15 20:14 PHST- 2021/02/02 00:00 [received] PHST- 2021/03/25 00:00 [revised] PHST- 2021/04/07 00:00 [accepted] PHST- 2021/04/16 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2021/04/15 20:14 [entrez] AID - S0378-5173(21)00397-5 [pii] AID - 10.1016/j.ijpharm.2021.120592 [doi] PST - ppublish SO - Int J Pharm. 2021 May 15;601:120592. doi: 10.1016/j.ijpharm.2021.120592. Epub 2021 Apr 20.