Selective Targeting of Cancer Cells by Oxidative Vulnerabilities with Novel Curcumin Analogs View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-04-24

AUTHORS

Christopher Pignanelli, Dennis Ma, Megan Noel, Jesse Ropat, Fadi Mansour, Colin Curran, Simon Pupulin, Kristen Larocque, Jianzhang Wu, Guang Liang, Yi Wang, Siyaram Pandey

ABSTRACT

Recently, research has focused on targeting the oxidative and metabolic vulnerabilities in cancer cells. Natural compounds like curcumin that target such susceptibilities have failed further clinical advancements due to the poor stability and bioavailability as well as the need of high effective doses. We have synthesized and evaluated the anti-cancer activity of several monocarbonyl analogs of curcumin. Interestingly, two novel analogs (Compound A and I) in comparison to curcumin, have increased chemical stability and have greater anti-cancer activity in a variety of human cancer cells, including triple-negative, inflammatory breast cancer cells. In particular, the generation of reactive oxygen species was selective to cancer cells and occurred upstream of mitochondrial collapse and execution of apoptosis. Furthermore, Compound A in combination with another cancer-selective/pro-oxidant, piperlongumine, caused an enhanced anti-cancer effect. Most importantly, Compound A was well tolerated by mice and was effective in inhibiting the growth of human triple-negative breast cancer and leukemia xenografts in vivo when administered intraperitoneally. Thus, exploiting oxidative vulnerabilities in cancer cells could be a selective and efficacious means to eradicate malignant cells as demonstrated by the curcumin analogs presented in this report with high therapeutic potential. More... »

PAGES

1105

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-017-01230-4

DOI

http://dx.doi.org/10.1038/s41598-017-01230-4

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https://app.dimensions.ai/details/publication/pub.1084946874

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28439094


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39 anti-cancer activity
40 anti-cancer effects
41 apoptosis
42 bioavailability
43 breast cancer
44 breast cancer cells
45 cancer
46 cancer cells
47 cells
48 chemical stability
49 clinical advancement
50 collapse
51 combination
52 comparison
53 compound A
54 compounds
55 curcumin
56 curcumin analogues
57 doses
58 effect
59 effective doses
60 efficacious means
61 enhanced anti-cancer effect
62 execution
63 execution of apoptosis
64 further clinical advancements
65 generation
66 greater anti-cancer activity
67 growth
68 high therapeutic potential
69 highest effective doses
70 human cancer cells
71 human triple-negative breast cancer
72 inflammatory breast cancer cells
73 leukemia xenografts
74 malignant cells
75 means
76 metabolic vulnerabilities
77 mice
78 mitochondrial collapse
79 monocarbonyl analogs
80 natural compounds
81 need
82 novel analogues
83 novel curcumin analog
84 oxidative vulnerability
85 oxygen species
86 piperlongumine
87 poor stability
88 potential
89 reactive oxygen species
90 report
91 research
92 selective targeting
93 species
94 stability
95 such susceptibility
96 susceptibility
97 targeting
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99 triple-negative breast cancer
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