Indirubin-3-monoxime and thymoquinone exhibit synergistic efficacy as therapeutic combination in in-vitro and in-vivo models of Lung cancer

Dera, Ayed A.; Rajagopalan, Prasanna; Fayi, Majed Al; Ahmad, Irfan; Chandramoorthy, Harish C.

doi:10.1007/s12272-020-01241-2

Cited by 18 publications

(14 citation statements)

References 33 publications

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“…Moreover, it has been found that the combination of TQ and genistein, a flavonoid found in soybeans[ 144 ], resulted in a higher induction of apoptosis in thyroid cancer cells than treatment with either agent alone[ 145 ]. In lung cancer, the combination of TQ and indirubin-3-monoxime, a drug derived from the traditional Chinese herbal remedy Danggui Longhui Wan[ 146 ], resulted in synergistic apoptotic and anti-migratory effects in vitro and synergistic tumor growth suppression in vivo [ 147 ]. At the molecular level, the dual treatment decreased the phosphorylation of survival-regulatory proteins Akt, mammalian target of rapamycin and NFkB and activated caspase 3 and p53 in animal tumors[ 147 ].…”

Section: Tq Effects Against Cancer Cellsmentioning

confidence: 99%

“…In lung cancer, the combination of TQ and indirubin-3-monoxime, a drug derived from the traditional Chinese herbal remedy Danggui Longhui Wan[ 146 ], resulted in synergistic apoptotic and anti-migratory effects in vitro and synergistic tumor growth suppression in vivo [ 147 ]. At the molecular level, the dual treatment decreased the phosphorylation of survival-regulatory proteins Akt, mammalian target of rapamycin and NFkB and activated caspase 3 and p53 in animal tumors[ 147 ]. Furthermore, combining TQ and piperine, the major alkaloid found in Piper nigrum L [ 148 ], resulted in a synergistic inhibition of breast cancer in vitro and in vivo [ 149 ].…”

Section: Tq Effects Against Cancer Cellsmentioning

confidence: 99%

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Therapeutic potential of thymoquinone in combination therapy against cancer and cancer stem cells

Fatfat¹,

Fatfat²,

Gali‐Muhtasib³

2021

WJCO

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The long-term success of standard anticancer monotherapeutic strategies has been hampered by intolerable side effects, resistance to treatment and cancer relapse. These monotherapeutic strategies shrink the tumor bulk but do not effectively eliminate the population of self-renewing cancer stem cells (CSCs) that are normally present within the tumor. These surviving CSCs develop mechanisms of resistance to treatment and refuel the tumor, thus causing cancer relapse. To ensure durable tumor control, research has moved away from adopting the monotreatment paradigm towards developing and using combination therapy. Combining different therapeutic modalities has demonstrated significant therapeutic outcomes by strengthening the anti-tumor potential of monotreatment against cancer and cancer stem cells, mitigating their toxic adverse effects, and ultimately overcoming resistance. Recently, there has been growing interest in combining natural products from different sources or with clinically used chemotherapeutics to further improve treatment efficacy and tolerability. Thymoquinone (TQ), the main bioactive constituent of Nigella sativa, has gained great attention in combination therapy research after demonstrating its low toxicity to normal cells and remarkable anticancer efficacy in extensive preclinical studies in addition to its ability to target chemoresistant CSCs. Here, we provide an overview of the therapeutic responses resulting from combining TQ with conventional therapeutic agents such as alkylating agents, antimetabolites and antimicrotubules as well as with topoisomerase inhibitors and non-coding RNA. We also review data on anticancer effects of TQ when combined with ionizing radiation and several natural products such as vitamin D3, melatonin and other compounds derived from Chinese medicinal plants. The focus of this review is on two outcomes of TQ combination therapy, namely eradicating CSCs and treating various types of cancers. In conclusion, the ability of TQ to potentiate the anticancer activity of many chemotherapeutic agents and sensitize cancer cells to radiotherapy makes it a promising molecule that could be used in combination therapy to overcome resistance to standard chemotherapeutic agents and reduce their associated toxicities.

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Section: Tq Effects Against Cancer Cellsmentioning

confidence: 99%

Section: Tq Effects Against Cancer Cellsmentioning

confidence: 99%

Therapeutic potential of thymoquinone in combination therapy against cancer and cancer stem cells

Fatfat¹,

Fatfat²,

Gali‐Muhtasib³

2021

WJCO

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“…[10][11] Thymoquinone exerts various pharmacological effects and has antiinflammatory, anticancer, antidiabetic, antiasthmatic, hypolipidemic, antihypertensive, nephroprotective, and antimicrobial activities. [12][13][14][15][16] The antibacterial effects of TQ and other N. sativa extracts have been determined against Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), Listeria monocytogenes, and Escherichia coli (E. coli). [17][18][19] Thymoquinone exerts inhibitory effects against gram-negative and gram-positive bacteria.…”

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confidence: 99%

Synergistic efficacies of thymoquinone and standard antibiotics against multi-drug resistant isolates

Dera

Ahmad

Rajagopalan

et al. 2021

SMJ

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The antimicrobial activity, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) of TQ were determined using an agar well diffusion method and broth microdilution assays, and the synergistic effect was evaluated using antibiotics in parallel. The disruptive effect of TQ on bacterial cell membranes was determined using scanning electron microscopy. The antivirulence Original Article properties of TQ, which include adherence and biofilm formation, were also investigated using adherence and biofilm formation assays, respectively. Results: Thymoquinone demonstrated bactericidal efficacy against 4/14 bacterial strains, with MIC range of 1.04-8.3 μg/mL and and MBC range of 10.41-66.66 μg/ mL. Thymoquinone showed synergism against Klebsiella pneumoniae, Staphylococcus epidermidis (American Type Culture Collection 12228), Staphylococcus aureus, and Staphylococcus epidermidis in combination with the tested antibiotics. Thymoquinone inhibited bacterial adhesion by 39%-54%, 48%-68%, and 61%-81% at 0.5 × MIC, 1 × MIC, and 2 × MIC, respectively. The tested bacterial strains significantly inhibited biofilm formation after treatment with various concentrations of TQ for 24 and 48 hours. Conclusion: The combinatory effect of TQ with antimicrobials should be considered when developing new antimicrobial therapy regimens to overcome multidrugresistant.

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“…Furthermore, TQ significantly reduced the expression of B-cell lymphoma 2 (Bcl2), an anti-apoptotic protein, and induced Bcl2-associated X (Bax) protein, a proapoptotic, leading to apoptosis of A549 cells ( Alam et al, 2022 ). In addition, the p-AKT, p-mTOR, caspase-3, p-53, and NF-κB expression levels were significantly reduced in TQ and TQ/indirubin-3-monoxime-treated A549 cells ( Dera et al, 2020 ). Also, TQ induced the antimitotic mechanism of A549 cells by its direct binding to the tubulin-MT network ( Acharya et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Curcumin, thymoquinone, and 3, 3′-diindolylmethane combinations attenuate lung and liver cancers progression

Saddiq

El‐Far²,

Abdullah³

et al. 2022

Front. Pharmacol.

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Cancer can develop due to abnormal cell proliferation in any body’s cells, so there are over a hundred different types of cancer, each with its distinct behavior and response to treatment. Therefore, many studies have been conducted to slow cancer progression and find effective and safe therapies. Nutraceuticals have great attention for their anticancer potential. Therefore, the current study was conducted to investigate the anticancer effects of curcumin (Cur), thymoquinone (TQ), and 3, 3′-diindolylmethane (DIM) combinations on lung (A549) and liver (HepG2) cancer cell lines’ progression. Results showed that triple (Cur + TQ + DIM) and double (Cur + TQ, Cur + DIM, and TQ + DIM) combinations of Cur, TQ, and DIM significantly increased apoptosis with elevation of caspase-3 protein levels. Also, these combinations exhibited significantly decreased cell proliferation, migration, colony formation activities, phosphatidylinositol 3-kinase (PI3K), and protein kinase B (AKT) protein levels with S phase reduction. Triple and double combinations of Cur, TQ, and DIM hindered tumor weight and angiogenesis of A549 and HepG2 implants in the chorioallantoic membrane model. Interestingly, Cur, TQ, and DIM combinations are considered promising for suppressing cancer progression via inhibiting tumor angiogenesis. Further preclinical and clinical investigations are warranted.

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Indirubin-3-monoxime and thymoquinone exhibit synergistic efficacy as therapeutic combination in in-vitro and in-vivo models of Lung cancer

Cited by 18 publications

References 33 publications

Therapeutic potential of thymoquinone in combination therapy against cancer and cancer stem cells

Therapeutic potential of thymoquinone in combination therapy against cancer and cancer stem cells

Synergistic efficacies of thymoquinone and standard antibiotics against multi-drug resistant isolates

Curcumin, thymoquinone, and 3, 3′-diindolylmethane combinations attenuate lung and liver cancers progression

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