In-silico and in-vitro anti-cancer potential of a curcumin analogue (1E, 6E)-1, 7-di (1H-indol-3-yl) hepta-1, 6-diene-3, 5-dione

Sufi, Shamim Akhtar; Adigopula, Lakshmi Narayana; Syed, Safiulla Basha; Mukherjee, Victor; Coumar, Mohane Selvaraj; Rao, H. Surya Prakash; Rajagopalan, Rukkumani

doi:10.1016/j.biopha.2016.11.040

Cited by 31 publications

(11 citation statements)

References 28 publications

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“…Synthetic compounds such as isoform derivatives and analogs are commonly synthesized to overcome the weakness and limitations possessed by its parent compound. Many studies have synthesized curcumin analogs to improve its anticancer properties [ 11 , 12 , 13 , 14 , 15 ]. Recently, a synthetic analog of curcumin possessing a lower molecular weight—namely, ( Z )-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-ene-1-one (DK1)—was synthesized in the form of a 100% pure crystal via the Baker–Venkataraman rearrangement method and confirmed using single X-ray crystallography [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

DK1 Induces Apoptosis via Mitochondria-Dependent Signaling Pathway in Human Colon Carcinoma Cell Lines In Vitro

Hussin

Aziz

Rahim

et al. 2018

IJMS

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Extensive research has been done in the search for innovative treatments against colon adenocarcinomas; however, the incidence rate of patients remains a major cause of cancer-related deaths in Malaysia. Natural bioactive compounds such as curcumin have been substantially studied as an alternative to anticancer drug therapies and have been surmised as a potent agent but, nevertheless, remain deficient due to its poor cellular uptake. Therefore, efforts now have shifted toward mimicking curcumin to synthesize novel compounds sharing similar effects. A synthetic analog, (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-ene-1-one (DK1), was recently synthesized and reported to confer improved bioavailability and selectivity toward human breast cancer cells. This study, therefore, aims to assess the anticancer mechanism of DK1 in relation to the induction of in vitro cell death in selected human colon cancer cell lines. Using the3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay, the cytotoxicity of DK1 towards HT29 and SW620 cell lines were investigated. Acridine orange/propidium iodide (AO/PI) dual-staining assay and flow cytometry analyses (cell cycle analysis, Annexin/V-FITC and JC-1 assays) were incorporated to determine the mode of cell death. To further determine the mechanism of cell death, quantitative real-time polymerase chain reaction (qRT-PCR) and proteome profiling were conducted. Results from this study suggest that DK1 induced changes in cell morphology, leading to a decrease in cell viability and subsequent induction of apoptosis. DK1 treatment inhibited cell viability and proliferation 48 h post treatment with IC50 values of 7.5 ± 1.6 µM for HT29 cells and 14.5 ± 4.3 µM for SW620 cells, causing cell cycle arrest with increased accumulation of cell populations at the sub-G0/G1phaseof 74% and 23%, respectively. Flow cytometry analyses showed that DK1 treatment in cancer cells induced apoptosis, as indicated by DNA fragmentation and depolarization of the mitochondrial membrane. qRT-PCR results show significant upregulation in the expression of caspase-9 in both HT29 and SW620 cell lines, further supporting that cell death induction by DK1 is via an intrinsic pathway. These outcomes, therefore, demonstrate DK1 as a potential anticancer agent for colon adenocarcinoma due to its anti-apoptotic attributes.

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Section: Introductionmentioning

confidence: 99%

DK1 Induces Apoptosis via Mitochondria-Dependent Signaling Pathway in Human Colon Carcinoma Cell Lines In Vitro

Hussin

Aziz

Rahim

et al. 2018

IJMS

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“…Natural products, that are a part of our daily diet or are easily obtained and disposable, have shown considerable anti-neoplastic effects without causing side effects [80]. Here we showed some examples of natural compounds extracted from plants and their role recently discovered as anti-leukemic agents.…”

Section: Monocillium Nordinii and Dandelion Plantmentioning

confidence: 75%

Natural Compounds: Molecular Weapons against Leukemia’s

Taverna¹,

Corrado

2017

J Leuk

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Nowadays cancer is one of the main reasons of death all over the world and it is estimated that deaths caused by cancer will grow dramatically in the next decades. Even if chemotherapy is the election therapy for solid tumors, as well as leukemias and lymphomas, cancer treatments are in continuous evolution trying to solve the problem of resistance mainly due to low accumulation of the drug in tumor cells (MDR). Natural compounds represent a valid alternative to treat several disease and recently the scientific community focus on these natural compounds and plant metabolites with therapeutic activities and low toxicities compared with synthetic ones.A combination therapy, that join conventional chemotherapy with natural plant metabolites, is now considered a new promising strategy to overcome MDR and reduce cellular toxicity; in particular, in leukemia due to its very complex origin and development of leukemogenesis.Here, we want to summarize and update the recent applications of natural compounds in the treatment of leukemia.

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“…Curcumin as a kind of plant polyphenol extracted from turmeric is the most important active ingredient of turmeric to play the pharmacological effect ( 15 ). Curcumin exhibits a variety of biological activities such as anti-inflammatory, antioxidation, anti-human immunodeficiency virus, anti-fibrosis and anticancer effects ( 16 – 18 ). During recent years, the defensive role of curcumin against apoptosis has been experimentally documented ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

Curcumin suppresses AGEs induced apoptosis in tubular epithelial cells via protective autophagy

et al. 2017

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Renal tubular cell apoptosis and tubular dysfunction is an important process underlying diabetic nephropathy (DN). Understanding the mechanisms underlying renal tubular epithelial cell survival is important for the prevention of kidney damage associated with glucotoxicity. Curcumin has been demonstrated to possess potent anti-apoptotic properties. However, the roles of curcumin in renal epithelial cells are yet to be defined. The present study investigated advanced glycation or glycoxidation end-product (AGE)-induced toxicity in renal tubular epithelial cells via several complementary assays, including cell viability, cell apoptosis and cell autophagy in the NRK-52E rat kidney tubular epithelial cell line. The extent of apoptosis was significantly increased in the NRK-52E cells following treatment with AGEs. The results also indicated that curcumin reversed this effect by promoting autophagy through the phosphoinositide 3-kinase/AKT serine/threonine kinase signaling pathway. These conclusions suggested that curcumin exerts a renoprotective effect in the presence of AGEs, at least in part by activating autophagy in NRK-52E cells. Collectively, these findings indicate that curcumin not only exerts renoprotective effects, however may also act as a novel therapeutic strategy for the treatment of diabetic nephropathy.

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In-silico and in-vitro anti-cancer potential of a curcumin analogue (1E, 6E)-1, 7-di (1H-indol-3-yl) hepta-1, 6-diene-3, 5-dione

Cited by 31 publications

References 28 publications

DK1 Induces Apoptosis via Mitochondria-Dependent Signaling Pathway in Human Colon Carcinoma Cell Lines In Vitro

DK1 Induces Apoptosis via Mitochondria-Dependent Signaling Pathway in Human Colon Carcinoma Cell Lines In Vitro

Natural Compounds: Molecular Weapons against Leukemia’s

Curcumin suppresses AGEs induced apoptosis in tubular epithelial cells via protective autophagy

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