Molecular mechanisms of curcumin and its semisynthetic analogues in prostate cancer prevention and treatment

Jordan, Brian C.; Mock, Charlotta D.; Thilagavathi, Ramasamy; Selvam, Chelliah

doi:10.1016/j.lfs.2016.03.036

Cited by 68 publications

(35 citation statements)

References 106 publications

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“…Curcumin, a natural polyphenol which is used as a food colourant, and herbal medicine in Asia. Curcumin has received a lot of attention recently due to its high‐safety profile and efficacy in treating various diseases . Potential anticancer activities associated with curcumin make it a promising therapeutic agent.…”

Section: Methodsmentioning

confidence: 99%

Synthesis, evaluation of cytotoxic properties of promising curcumin analogues and investigation of possible molecular mechanisms

et al. 2017

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Curcumin is a popular, plant-derived compound that has been extensively investigated for diverse range of biological activities. Anticancer activity against various types of cancers and high-safety profile associated with curcumin makes it very attractive. In this study, we report the synthesis and evaluation of pyrazole and click chemistry curcumin analogues for Head and Neck cancer. MTT assay against head and neck cancer cell lines CAL27 and UM-SCC-74A revealed the micromolar potency of the synthesized compounds. To determine the possible molecular mechanisms, effect of these analogues in the expression of pSTAT3, pFAK, pERK1/2 and pAKT was studied. Interestingly, compounds 2 and 5 significantly inhibited the pSTAT3 (Tyr 705) phosphorylation. As far as other compounds, they showed potent cytotoxicity against CAL27; however, these compounds did not show any activity on pSTAT3 phosphorylation at IC 50 concentration level. Molecular docking studies revealed the possible binding mode of pyrazole compound 2 in the SH2 domain of STAT3. K E Y W O R D Sclick chemistry curcumin analogue, curcumin, head and neck squamous cell carcinoma, pyrazole analogue Curcumin, a natural polyphenol which is used as a food colourant, and herbal medicine in Asia. Curcumin has received a lot of attention recently due to its high-safety profile and efficacy in treating various diseases.[1-3] Potential anticancer activities associated with curcumin make it a promising therapeutic agent. Apart from anticancer activity, it has shown antioxidant, anti-inflammatory, chemopreventive, chemotherapeutic, antimicrobial and antifungal activities. Curcumin (Figure 1) is being vigorously studied for its effect against breast cancer, prostate cancer, liver cancer, ovarian cancer and cervical cancer.[4] It demonstrated cytotoxic effects against cancer cell lines and cytoprotective effects on non-cancer cells. One of the important aspects of curcumin is its high-safety profile of up to 12 g per day oral administration.[5]Nevertheless, there are a number of challenges, low aqueous solubility, poor absorption and rapid metabolism that limits its therapeutic efficacy.[6] Curcumin can exist as a tautomeric mixture of keto and enol forms in solutions, and the enol form was found to be responsible for the rapid degradation of the curcumin. Chakraborti et al., [7] found that the stability of curcumin was improved when the central diketone moiety of the curcumin was replaced by isooxazole and pyrazole groups. Structural modifications of curcumin were proven to be a meaningful approach to discover analogues with enhanced properties. [8][9][10][11][12] Conjugates of curcumin with β-and γ-cyclodextrin, liposomal and loaded nanoparticles and nanoemulsion are some of the lipid-based colloidal system that has been employed to enhance water solubility and improving its bioavailability.[13] Recent work supports the

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Section: Methodsmentioning

confidence: 99%

Synthesis, evaluation of cytotoxic properties of promising curcumin analogues and investigation of possible molecular mechanisms

et al. 2017

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“…In proteomic identification of curcumin treated MCF-7 cells, 3-PGDH and ERP29 were found to be upregulated and TDP-43, SF2/ASF, and eIF3i were downregulated, suggesting curcumin induced apoptosis in breast cancer [64]. However, due to its lack of aqueous solubility, high concentrations are required to demonstrate potential chemotherapeutic efficacy [66]. While many researchers are optimistic regarding curcumin’s potential effectiveness against cancer, there is evidence to show that curcumin has no therapeutic benefits despite many published articles and clinical trials [67].…”

Section: Traditional Chinese Medicines (Tcms) As Anti-cancer Agentsmentioning

confidence: 99%

Understanding the Effectiveness of Natural Compound Mixtures in Cancer through Their Molecular Mode of Action

Aung

Kortschak

et al. 2017

IJMS

262

149

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Many approaches to cancer management are often ineffective due to adverse reactions, drug resistance, or inadequate target specificity of single anti-cancer agents. In contrast, a combinatorial approach with the application of two or more anti-cancer agents at their respective effective dosages can achieve a synergistic effect that boosts cytotoxicity to cancer cells. In cancer, aberrant apoptotic pathways allow cells that should be killed to survive with genetic abnormalities, leading to cancer progression. Mutations in apoptotic mechanism arising during the treatment of cancer through cancer progression can consequently lead to chemoresistance. Natural compound mixtures that are believed to have multiple specific targets with minimal acceptable side-effects are now of interest to many researchers due to their cytotoxic and chemosensitizing activities. Synergistic interactions within a drug mixture enhance the search for potential molecular targets in cancer cells. Nonetheless, biased/flawed scientific evidence from natural products can suggest false positive therapeutic benefits during drug screening. In this review, we have taken these factors into consideration when discussing the evidence for these compounds and their synergistic therapeutic benefits in cancer. While there is limited evidence for clinical efficacy for these mixtures, in vitro data suggest that these preparations merit further investigation, both in vitro and in vivo.

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“…An interesting advantage for curcumin is its anti-cancer effects. This advantage makes curcumin a suitable radiosensitizer [111][112][113].…”

Section: Curcuminmentioning

confidence: 99%

Radiation Protection and Mitigation by Natural Antioxidants and Flavonoids: Implications to Radiotherapy and Radiation Disasters

Yahyapour

Shabeeb

Cheki

et al. 2018

CMP

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Molecular mechanisms of curcumin and its semisynthetic analogues in prostate cancer prevention and treatment

Cited by 68 publications

References 106 publications

Synthesis, evaluation of cytotoxic properties of promising curcumin analogues and investigation of possible molecular mechanisms

Synthesis, evaluation of cytotoxic properties of promising curcumin analogues and investigation of possible molecular mechanisms

Understanding the Effectiveness of Natural Compound Mixtures in Cancer through Their Molecular Mode of Action

Radiation Protection and Mitigation by Natural Antioxidants and Flavonoids: Implications to Radiotherapy and Radiation Disasters

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