Curcumin Analogs Induce Apoptosis and G2/M Arrest In 4T1 Murine Triple-Negative Breast Cancer Cells

Abstract

Chemotherapy is the first-line treatment for triple-negative breast cancer (TNBC), yet toxicity and resistance effects have been the current problems. Curcumin,a natural compound, has been reported to exert anti-proliferative effects on various cancer cells, including breast carcinoma cells. However, the β-diketone moiety influences the stability of curcumin. Curcumin analogs, pentagamavunon-0 (PGV-0), and pentagamavunon-1 (PGV-1) were synthesized to improve the stability and activity of curcumin by modified the β-diketone moiety into mono-ketone pentanone. In this study, we evaluated the cytotoxicity, inhibition of cell cycle progression, and induction of apoptosis of curcumin and its analogs (PGV-0 and PGV-1) in murine triple-negative breast cancer 4T1 cell line. The cytotoxic evaluation was done by MTT assay, while apoptosis induction and cell cycle evaluation was performed by annexin V staining and detected by flow cytometry. Curcumin and its analogs, PGV-0, and PGV-1, significantly inhibit the viability of 4T1 breast cancer cells with an IC50 value of 34.34µg/mL, 13.76µg/mL and 38.21μg/mL, respectively. Apoptosis analysis with a dose of 10µg/mL and 15µg/mL in 4T1 breast cancer cells showed that curcumin and its analogs effectively induce apoptotic in a dose-dependent manner. In cell cycle analysis using a dose of 15µg/mL, curcumin inhibited the cell cycle progression in the S phase, whereas PGV-0 and PGV-1 inhibited the cell cycle in the G2/M phase. It could be concluded that curcumin analogs, PGV-0 and PGV-1, have higher potential to be developed as anti-cancer agents by inducing cell cycle arrest and apoptosis in triple-negative breast cancer.

Aaptamine-rich Fraction from the Indonesian Marine Sponge, Aaptos suberitoides, Exhibits a Cytotoxic Effect on DLD-1 Colorectal Cancer Cells

“…The MTT assay method refers to [26] . Colorectal sulfate indicating the total organic compound contained, Dragendorff's reagent indicating tertiary amine moiety, and ninhydrin indicating primary and secondary amines.…”

Effect of SNEDDS Loading Pentagamavunon-0 on Memory Impairment and Neurogenesis in Mice with Monosodium Glutamate-Induced Alzheimer’s Disease-Like Symptoms

“…The various pharmacological activities of pentagamavunon-0 (PGV-0), an analog of curcumin, have been described in several studies [14][15][16][17][18][19], including its role as an antioxidant.…”

“…These findings suggest that revitalizing adult hippocampal neurogenesis holds enormous potential as an effective therapeutic target for AD. The various pharmacological activities of pentagamavunon-0 (PGV-0), an analog of curcumin, have been described in several studies [14–19], including its role as an antioxidant. Its chemical structure includes phenolic hydroxy and methoxy groups in the ortho position of both aromatic rings, significantly contributing to its potent antioxidant properties and free radical scavenging abilities [20,21].…”

Synthesis and Antioxidant Actiivty of Some Dibenzylidene-Cyclohexanones

“…As endogenous antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GSH), and catalase (Murray, 2003) are produced by our body, exogenous antioxidants come from intakes such as fruits, vegetables, food supplement, herbs, spices, and drugs. The nature provides wide arrays of good external antioxidants with important substances such as vitamin E, vitamin C, and flavonoids are some of the examples (Nimse and Pal, 2015).…”

“…Curcumin analogs are the result of curcumin structure modification. Many of them have been studied for their biological activities (Tomeh et al, 2019;Allegra et al, 2016;Murwanti et al, 2020), including as antioxidant (Simon et al, 2018). Some studies have reported the discovery of compounds in this type, such as Pentagamavunon-0 (PGV-0, Pentagamavunon-5 (PGV-5), Heksagamavunon-5 (HGV-5) (Figure 1) (Reksohadiprodjo et al, 2004) (Yuwono & Oetari, 2004, Tetrahydropentagamavunon-0 (THPGV-0) (Ritmaleni & Simbara, 2010), Tetrahydropentagamavunon-1 (THPGV-1) (Ikawati et al, 2018), and Tetrahydropentagamavunon-5 (THPGV-5).…”