Abstract
A new curcumin analog, CCA-1.1, induces cell death and cell cycle arrest in WiDr colon cancer cells via ROS generation
Highlights
Chemoprevention-curcumin analog 1.1 (CCA-1.1) or2,5-bis-(4-hydroxy-3,5-dimethyl benzylidene)-cyclopentanol (Fig. 1) is a new Pentagamavunone-1 (PGV-1) analog synthesized by Utomo et al (2021) to construct a more compelling candidate for an anticancer drug
We suggest that CCA-1.1 can possibly combat PGV-1 as an anticancer candidate, owing to the higher cytotoxic effect on WiDr cells and less toxicity on NIH-3T3 cells
To elucidate the correlation of cell cycle arrest and cellular senescence in the treatment of CCA-1.1, we employed Senescence-Associated (SA)-β-galactosidase assay and employed doxorubicin to trigger senescence in cells (Kuilman et al, 2010; Yang et al, 2012). We demonstrated that both doses of CCA-1.1 and PGV-1 cause cellular senescence in WiDr cells (p < 0.001) at an equal level with doxorubicin (Fig. 5)
Summary
2,5-bis-(4-hydroxy-3,5-dimethyl benzylidene)-cyclopentanol (Fig. 1) is a new Pentagamavunone-1 (PGV-1) analog synthesized by Utomo et al (2021) to construct a more compelling candidate for an anticancer drug. We reported CCA-1.1 potency on colon cancer through a bioinformatic exploration (Wulandari et al, 2020) and its effect against MCF-7 and T47D breast cancer cells (Novitasari et al, 2021; Wulandari et al, 2021a, 2021b). CCA-1.1 showed a better cytotoxic effect than PGV-1 on WiDr colon cancer cells (Utomo et al, 2021). Considering that CCA-1.1 has a similar structure backbone to PGV-1, it might have a comparable or more outstanding anticancer activity. The superiority of PGV-1 revealed a remarkable cytotoxic effect on colon cancer cells beyond many recommended drugs for treating colon cancer such as 5-fluorouracil, cisplatin, and doxorubicin (Meiyanto et al, 2018; Wulandari et al, 2018). The antiproliferative activity of PGV-1 is related to a unique G2/M cell cycle arrest, apoptosis, senescence induction, reactive oxygen species (ROS) accumulation (Hermawan et al, 2011; Lestari et al, 2019; Meiyanto et al, 2014, 2018, 2019), and inhibition of nuclear
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