Potent anti-cancer effects of less polar Curcumin analogues on gastric adenocarcinoma and esophageal squamous cell carcinoma cells

Abstract

Curcumin and its chalcone derivatives inhibit the growth of human cancer cells. It is reported that replacement of two OH groups in curcumin with less polar groups like methoxy increases its anti-proliferative activity. In this study, we explored benzylidine cyclohexanone derivatives with non-polar groups, to see if they possess increased anti-cancer activity. Novel 2,6-bis benzylidine cyclohexanone analogues of curcumin were synthesized, and their inhibitory effects on gastric adenocarcinoma (AGS) and esophageal squamous cell carcinoma (KYSE30) cancer cells were studied using an MTT assay. Cell apoptosis was detected by EB/AO staining, and cell cycle was analyzed by flow cytometry. Real-time PCR was performed for gene expression analysis. All synthesized analogues were cytotoxic toward gastric and esophageal cancer cells and showed lower IC50 values than curcumin. Treatment with 2,6-Bis-(3-methoxy-4-propoxy-benzylidene)-cyclohexanone (BM2) was 17 times more toxic than curcumin after 48 h incubation. All novel compounds were more effective than curcumin in apoptosis induction and cell cycle arrest at G1 phase. These results suggest that less polar analogues of curcumin have potent cytotoxicity in vitro. However, they need to be investigated further, especially with animal tumor models, to confirm their chemotherapeutic activity in vivo.

Oral curcumin for radiation dermatitis: a URCC NCORP study of 686 breast cancer patients

“…Curcumin is limited by its hydrophobic nature, poor water solubility, low bioavailability, and chemical instability. New advances in pharmaceutical strategies, such as nanoencapsulation, may overcome these limitations [1, 18, 21, 23]. Additionally, the isolation of curcumin from the other constituents in turmeric may reduce its therapeutic potential.…”

“…Additionally, the isolation of curcumin from the other constituents in turmeric may reduce its therapeutic potential. Curcumin’s demonstrated therapeutic benefit and increased bioavailability when used as an adjunct drug in therapy supports this argument [1, 4, 18, 21, 23, 33]. A future trial exploring turmeric or a combined nutraceutical therapy for radiation dermatitis may yield positive results.…”

Chemopreventive and therapeutic potential of curcumin in esophageal cancer: Current and future status

“…Another study investigated the inhibitory effects of new 2,6‐bis benzylidine cyclohexanone analogs of curcumin on gastric adenocarcinoma (AGS) and esophageal squamous cell carcinoma (KYSE30) cancer cells. The results revealed that all synthetic analogs are cytotoxic toward esophageal and gastric cancer cells and more promising than curcumin in cell cycle arrest at G 1 phase and apoptosis induction . Furthermore, these studies recommend that curcumin and related cyclohexanone analogs are effective anticancer agents with various in vitro effects on esophageal cancer cell lines.…”

Curcumin, a Natural Golden Drug and Its Anticancer Aspects From Synthesis to Delivery: A Review

“…Of all the medicinal plants, Curcumin, an important phytochemical of herb Curcuma longa of the ginger family, has been of great interest. In 1870, Curcumin was extracted from Curcuma longa (turmeric plant) for the first time in the crystalline state [42,43]. Multi biofunctionality properties of Curcumin and its derivatives have received enormous attention by the researchers such as antibacterial, antimalarial, antimutagenic, anti-tumor, antioxidant, antiinflammatory activities etc.…”