Anticancer Effect of a Novel 2-Arylidene-4,7-dimethyl indan-1-one Against Human Breast Adenocarcinoma Cell Line by G&lt;SUB&gt;2&lt;/SUB&gt;/M Cell Cycle Arrest

Rajagopalan, Prasanna; Harish, C. C.

doi:10.3727/096504010x12704916124747

Cited by 16 publications

(17 citation statements)

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“…Our results were in agreement and another way of confirming the induction of apoptosis by MLT-401. It is well established from the literature [37] and our own previous investigations [17, 21] have shown that the cells which get accumulated in the M4 fraction were apoptotic cells.…”

Section: Discussionmentioning

confidence: 93%

“…Many studies have assessed various other arylidene derivatives exhibiting antibacterial [23], antifungal [24], or anticancer [25, 26] activities. Other members of our study group have also reported anti-cancer properties [17, 21] for a few derivatives of this family.…”

Section: Discussionmentioning

confidence: 99%

“…MLT-401 was added at the desired concentration to the medium and the cells were incubated for 72 h at 37°C in a 5% CO 2 incubator. After 72 h, the cells were fixed in 70% ethanol and stored at -20°C till acquisition using a flowcytometer; 10, 000 events were acquired and % percentage of cell population in different cell cycle stages with respect to control was calculated [21]. …”

Section: Methodsmentioning

confidence: 99%

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Natural Hypoxia is Not a Limiting Factor in Evaluating the Novel Arylidene Derivative MLT-401 Against an In Vitro Colorectal Cancer Model

Bin-Jaliah¹

2018

Cell Physiol Biochem

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Background/Aims: Cancer cells in vivo develop resistance to many anti-tumor drugs. One known factor to influence such drug resistance is hypoxia, which is an important component of the tumor microenvironment. Standard cancer lines mostly do not exhibit a cellular hypoxic microenvironment and there is a paucity of information on the efficacy of lead molecules in both cellular- and environment-induced hypoxic conditions. Therefore, in the present study, we have evaluated the efficacy of the arylidene derivative MLT-401, a lead molecule showing activity against colorectal cancer model using the HCT 116 cell line and CCD-80-C control cells in normoxic and natural (marginal) hypoxic conditions, which is usually observed in high-altitude regions. Methods: The efficacy of MLT-401 on HCT 116 and CCD-80-C cells were tested in both normoxia and marginal hypoxia conditions. MTT assay was used to evaluate cell proliferation, Annexin V binding assay for apoptotic cell quantification and PI staining for cell cycle were done by flow cytometry. Induction of pro-apoptotic marker BAX and anti-apoptotic Bcl-2 were assessed by western blot. Bcl-2/BAX ratio was calculated based on protein expression by western blotting and bands were quantified by Image J software. Results: Analysis of cell proliferation showed an average 10-fold reduction in the inhibition of HCT 116 cells in hypoxic conditions with approximately 500 nM MLT-401, while there was no significant change noted in marginal hypoxic conditions. A proportionate increase in the number of apoptotic cells and large M4 fraction of 10.5% and 26.7% of HCT116 against 6.3% of control cells in cell cycle assessment with MLT-401 concentrations ranging from 250 to 500 nM respectively clearly demonstrated anti-cancer activity. A Bcl-2/BAX ratio of < 1 showed that the induction of apoptosis was the gross mechanism underlying the inhibition of HCT 116 cells by MLT-401. Conclusion: Collectively, these results show MLT-401 as an effective anti-colorectal cancer lead molecule irrespective of normoxia or natural hypoxia.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Natural Hypoxia is Not a Limiting Factor in Evaluating the Novel Arylidene Derivative MLT-401 Against an In Vitro Colorectal Cancer Model

Bin-Jaliah¹

2018

Cell Physiol Biochem

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“…Structure of FXY-1 (IUPAC-2-arylidene-4, 7-dimethyl indan-1-one) is shown in Figure 1b. FXY-1 was proven against breast adenocarcinoma cells and lung cancer cells (Prasanna & Harish, 2010). FXY-1 was reported to induce apoptosis in human lung carcinoma cells through inhibiting AKT-mitochondrial pathway (Rajagopalan et al, 2016).…”

Section: Practical Applicationsmentioning

confidence: 99%

Rational combinations of indirubin and arylidene derivatives exhibit synergism in human non‐small cell lung carcinoma cells

et al. 2019

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Rational combination of natural and synthetic derivatives to treat lung cancer has advantages of both efficacy and safety. Herein, the combination of indirubin‐3‐monoxime (I3M), a chemical derived from Chinese herbal medicine and FXY‐1, a synthetic arylidene derivative, was tested for combined activity in lung cancer cells. A dose‐dependent synergistic reduction in cell viability was recorded with the combinations in A549 and NCI‐H460 cells. Combination treatments of I3M and FXY‐1 showed antimetastatic effects in both cells. Cell cycle analysis revealed G1 growth phase reduction with subsequent accumulation of sub G0 contents. Annexin V assay revealed higher apoptotic cells with combinations compared to individual treatments. I3M + FXY‐1 combination significantly decreased the antiapoptotic Bcl‐2 protein and increased pro‐apoptotic Bax protein levels. These results demonstrate efficacy of I3M + FXY‐1 in lung cancer cells and suggest further preclinical research in animal models to develop it into a new form combination chemotherapeutic against lung cancer. Practical applications Current investigation will open new options in rational combinations of natural and synthetic compounds to treat cancer. The observed efficacy and safety of the combinations will add to the advantage of higher therapeutic window in formulating treatment regimens. The antimetastatic effects by the combinations provides promising efficacy in controlling the lung cancer progression. A detailed in vivo investigation is recommended to transform the combinations to novel chemotherapeutic options against lung cancer.

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“…Arylidene, with potential antitumor properties, belongs to this class of drug. We previously reported that an arylidene derivative (FXY-1) was effective against breast and lung cancer cells [8,9]. Based on these observations, we synthesized structural analogs of this compound by rational drug design and docked them with Akt to check the enzyme-compound affinity.…”

Section: Introductionmentioning

confidence: 99%

IOX-101, a novel small molecule, reduces AML cell proliferation by Akt enzyme inhibition

Rajagopalan¹,

Raju²,

Aseeri³

et al. 2018

ARCH BIOL SCI BELGRA

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Cancer of the blood continues to be a major mortality factor globally. Arylidene compounds are well known for their anticancer effects. Here we describe the biological efficacy of IOX-101, a potential lead-compound of arylidene in acute myeloid leukemia (AML). Initially, molecular docking analysis was performed to check the binding efficacy of the compound with protein kinase B (Akt). The ability of the molecule to inhibit AML proliferation was assessed in THP-1 and Kasumi-6 cells by a standard MTT assay. Hoechst 333258/propidium iodide (PI) staining was carried out to analyze the nuclear damage. Flow cytometry was performed to check the apoptotic and cell cycle changes in THP-1 cells. The effect of IOX-101 on Akt phosphorylation was assessed by Western blot analysis. Molecular docking revealed interaction and binding of IOX-101 with the active site of Akt enzyme. The compound reduced proliferation of both AML cell lines in a dose-responsive way. Nuclear staining and cell cycle results revealed DNA damage by IOX-101 in THP-1 cells, and a significant increase in early and late phase apoptotic cells. A dose-dependent dephosphorylation of Akt (Ser 473) by IOX-101 was observed, which indicated allosteric inhibition of Akt by the compound. Our results showed that the DNA damage-mediated antiproliferative effect of IOX-101 in AML cells was mediated by Akt enzyme inhibition, and that this molecule possesses an effective chemotherapeutic potential against AML.

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Anticancer Effect of a Novel 2-Arylidene-4,7-dimethyl indan-1-one Against Human Breast Adenocarcinoma Cell Line by G<SUB>2</SUB>/M Cell Cycle Arrest

Cited by 16 publications

References 0 publications

Natural Hypoxia is Not a Limiting Factor in Evaluating the Novel Arylidene Derivative MLT-401 Against an In Vitro Colorectal Cancer Model

Natural Hypoxia is Not a Limiting Factor in Evaluating the Novel Arylidene Derivative MLT-401 Against an In Vitro Colorectal Cancer Model

Rational combinations of indirubin and arylidene derivatives exhibit synergism in human non‐small cell lung carcinoma cells

IOX-101, a novel small molecule, reduces AML cell proliferation by Akt enzyme inhibition

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