Curcumin analogs exhibit anti-cancer activity by selectively targeting G-quadruplex forming c-myc promoter sequence

Pandya, Nirali; Khan, Eshan; Jain, Neha; Satham, Lakshminarayana; Singh, Rahul; Makde, Ravindra D.; Mishra, Amit; Kumar, Amit

doi:10.1016/j.biochi.2020.11.006

Cited by 25 publications

(18 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In particular, the exposure of myeloma cells to D089 induced endoplasmic reticulum stress, thus resulting in pyroptotic cell death, as evidenced by the appearance of a “ballooning” morphology associated with increased levels of the cleaved form of the inflammatory caspase 1 and of IL1-β as well as of gasdermin D cleavage and of HMGB1 cytoplasm translocation [ 61 ]. Recently, a Curcumin derivative, the synthetic 3,4-dimethoxy benzaldehyde Cur-4, has been recognized as a promising candidate for direct G4-mediated inhibition of MYC expression [ 62 ]. In particular, Cur-4 exhibited strong affinity and selectivity for G4 over duplex MYC DNA by binding at terminal G-tetrads [ 62 ].…”

Section: Targeting G-quadruplex Structures In Cancermentioning

confidence: 99%

“…Recently, a Curcumin derivative, the synthetic 3,4-dimethoxy benzaldehyde Cur-4, has been recognized as a promising candidate for direct G4-mediated inhibition of MYC expression [ 62 ]. In particular, Cur-4 exhibited strong affinity and selectivity for G4 over duplex MYC DNA by binding at terminal G-tetrads [ 62 ]. The compound was found to significantly reduce the expression of MYC and to exert an anti-cancer activity in a panel of cancer cells as well as in multicellular tumor spheroid models [ 62 ].…”

Section: Targeting G-quadruplex Structures In Cancermentioning

confidence: 99%

“…In particular, Cur-4 exhibited strong affinity and selectivity for G4 over duplex MYC DNA by binding at terminal G-tetrads [ 62 ]. The compound was found to significantly reduce the expression of MYC and to exert an anti-cancer activity in a panel of cancer cells as well as in multicellular tumor spheroid models [ 62 ].…”

Section: Targeting G-quadruplex Structures In Cancermentioning

confidence: 99%

See 2 more Smart Citations

On the Road to Fight Cancer: The Potential of G-Quadruplex Ligands as Novel Therapeutic Agents

Alessandrini

Recagni

Zaffaroni

et al. 2021

IJMS

View full text Add to dashboard Cite

Nucleic acid sequences able to adopt a G-quadruplex conformation are overrepresented within the human genome. This evidence strongly suggests that these genomic regions have been evolutionary selected to play a pivotal role in several aspects of cell biology. In the present review article, we provide an overview on the biological impact of targeting G-quadruplexes in cancer. A variety of small molecules showing good G-quadruplex stabilizing properties has been reported to exert an antitumor activity in several preclinical models of human cancers. Moreover, promiscuous binders and multiple targeting G-quadruplex ligands, cancer cell defense responses and synthetic lethal interactions of G-quadruplex targeting have been also highlighted. Overall, evidence gathered thus far indicates that targeting G-quadruplex may represent an innovative and fascinating therapeutic approach for cancer. The continued methodological improvements, the development of specific tools and a careful consideration of the experimental settings in living systems will be useful to deepen our knowledge of G-quadruplex biology in cancer, to better define their role as therapeutic targets and to help design and develop novel and reliable G-quadruplex-based anticancer strategies.

show abstract

Section: Targeting G-quadruplex Structures In Cancermentioning

confidence: 99%

Section: Targeting G-quadruplex Structures In Cancermentioning

confidence: 99%

Section: Targeting G-quadruplex Structures In Cancermentioning

confidence: 99%

See 1 more Smart Citation

On the Road to Fight Cancer: The Potential of G-Quadruplex Ligands as Novel Therapeutic Agents

Alessandrini

Recagni

Zaffaroni

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…A large number of studies have confirmed that curcumin can regulate anti-tumor molecule targets in cancer (Pandya et al, 2021), which is expected to achieve a breakthrough in the research of natural targeted drugs. Curcumin can not only inhibit the proliferation and metastasis, but also attenuate the chemotherapy resistance of cancer cells (Su et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Curcumin played an anti-cancer role in colorectal cancer via mediating circ_KIAA1199-related regulatory axis

Sun

Liu

2022

Food Sci. Technol

View full text Add to dashboard Cite

“…In particular, numerous small molecules such as anilinoquinazoline, quindoline, carbazole, acridone, phenanthroline, curcumin, and their analogs have been identified, which bind and stabilize the c-myc G4 motif. As a result, the transcription and translation activity of c-myc gene get downregulated 54 , 62 – 65 . Additionally, water-soluble dyes have also shown strong interaction with c-myc G4 as fluorescence probes 66 , 67 .…”

Section: Introductionmentioning

confidence: 99%

Piperine analogs arrest c-myc gene leading to downregulation of transcription for targeting cancer

Pandya

Kumar

2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

G-quadruplex (G4) structures are considered a promising therapeutic target in cancer. Since Ayurveda, Piperine has been known for its medicinal properties. Piperine shows anticancer properties by stabilizing the G4 motif present upstream of the c-myc gene. This gene belongs to a group of proto-oncogenes, and its aberrant transcription drives tumorigenesis. The transcriptional regulation of the c-myc gene is an interesting approach for anticancer drug design. The present study employed a chemical similarity approach to identify Piperine similar compounds and analyzed their interaction with cancer-associated G-quadruplex motifs. Among all Piperine analogs, PIP-2 exhibited strong selectivity, specificity, and affinity towards c-myc G4 DNA as elaborated through biophysical studies such as fluorescence emission, isothermal calorimetry, and circular dichroism. Moreover, our biophysical observations are supported by molecular dynamics analysis and cellular-based studies. Our study showed that PIP-2 showed higher toxicity against the A549 lung cancer cell line but lower toxicity towards normal HEK 293 cells, indicating increased efficacy of the drug at the cellular level. Biological evaluation assays such as TFP reporter assay, quantitative real-time PCR (qRT- PCR), and western blotting suggest that the Piperine analog-2 (PIP-2) stabilizes the G-quadruplex motif located at the promoter site of c-myc oncogene and downregulates its expression. In conclusion, Piperine analog PIP-2 may be used as anticancer therapeutics as it affects the c-myc oncogene expression via G-quadruplex mediated mechanism.

show abstract

Curcumin analogs exhibit anti-cancer activity by selectively targeting G-quadruplex forming c-myc promoter sequence

Cited by 25 publications

References 88 publications

On the Road to Fight Cancer: The Potential of G-Quadruplex Ligands as Novel Therapeutic Agents

On the Road to Fight Cancer: The Potential of G-Quadruplex Ligands as Novel Therapeutic Agents

Curcumin played an anti-cancer role in colorectal cancer via mediating circ_KIAA1199-related regulatory axis

Piperine analogs arrest c-myc gene leading to downregulation of transcription for targeting cancer

Contact Info

Product

Resources

About