Combinatorial therapy of Thymoquinone and Emodin synergistically enhances apoptosis, attenuates cell migration and reduces stemness efficiently in breast cancer

Bhattacharjee, Mousumi; Upadhyay, Priyanka; Sarker, Sushmita; Basu, Arijita; Das, Shaswati; Ghosh, Avijit; Ghosh, Swatilekha; Adhikary, Arghya

doi:10.1016/j.bbagen.2020.129695

Cited by 30 publications

(21 citation statements)

References 32 publications

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“…In another study, Das et al [ 138 ] demonstrated the synergistic anti-proliferative and apoptotic potential of combining TQ with diosgenin, a natural steroidal saponin isolated from several plants such as Trigonella foenum-graecum [ 139 ], in squamous cell carcinoma in vitro and in a sarcoma 180-induced mouse model. Recently, Bhattacharjee et al [ 140 ] investigated the combined effect of TQ with emodin, which is a natural anthraquinone obtained from various herbs including Rheum palmatum [ 141 ]. The results revealed that the dual treatment triggered a synergistic apoptotic response in breast cancer cells and enhanced the reduction of cancer cell migration compared to monotreatment by downregulating two important molecular players, namely focal adhesion kinase and integrin β1.…”

Section: Tq Effects Against Cancer Cellsmentioning

confidence: 99%

“…The results revealed that the dual treatment triggered a synergistic apoptotic response in breast cancer cells and enhanced the reduction of cancer cell migration compared to monotreatment by downregulating two important molecular players, namely focal adhesion kinase and integrin β1. In an ex ovo chorioallantoic membrane xenograft model, TQ and emodin were found to suppress the tumor growth and limit the migration of tumor cells to the liver and lung of the chick embryo[ 140 ]. Combining low doses of TQ and ferulic acid, obtained from Ferula asafetida plant[ 142 ], potently inhibited the proliferation of breast cancer cells, while single treatments did not exhibit any inhibitory effects[ 143 ].…”

Section: Tq Effects Against Cancer Cellsmentioning

confidence: 99%

“…The combined treatment of TQ and emodin improved the elimination of breast CSCs as demonstrated by the enhanced reduction in mammospheres forming efficiency and in CD44 + /CD24 - CSCS population compared to single treatments. Moreover, it downregulated the stemness promoting transcription factors Oct4 and SOX2[ 140 ].…”

Section: Tq Effects Against Cancer Stem 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%

Section: Tq Effects Against Cancer Stem Cellsmentioning

confidence: 99%

See 1 more Smart Citation

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

Fatfat¹,

Fatfat²,

Gali‐Muhtasib³

2021

WJCO

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“…Combined treatment with emodin 5 µg/mL and thymoquinone 1 µg/mL inhibited cell migration and FAK, pFAK, and integrin β1 proteins were down-regulated in both cell lines. In ex vivo CAM model combination treatment also inhibited tumor growth and metastasis [ 105 ]. Again, in a study conducted in MCF7 cells, emodin was reported to cause 28.89–47.64% apoptotic death in the concentration range of 25–100 µmol/L.…”

Section: Anticancer Activity Of Emodinmentioning

confidence: 99%

Is Emodin with Anticancer Effects Completely Innocent? Two Sides of the Coin

Akkol

Tatlı

Karatoprak

et al. 2021

Cancers

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Many anticancer active compounds are known to have the capacity to destroy pathologically proliferating cancer cells in the body, as well as to destroy rapidly proliferating normal cells. Despite remarkable advances in cancer research over the past few decades, the inclusion of natural compounds in researches as potential drug candidates is becoming increasingly important. However, the perception that the natural is reliable is an issue that needs to be clarified. Among the various chemical classes of natural products, anthraquinones have many biological activities and have also been proven to exhibit a unique anticancer activity. Emodin, an anthraquinone derivative, is a natural compound found in the roots and rhizomes of many plants. The anticancer property of emodin, a broad-spectrum inhibitory agent of cancer cells, has been detailed in many biological pathways. In cancer cells, these molecular mechanisms consist of suppressing cell growth and proliferation through the attenuation of oncogenic growth signaling, such as protein kinase B (AKT), mitogen-activated protein kinase (MAPK), HER-2 tyrosine kinase, Wnt/-catenin, and phosphatidylinositol 3-kinase (PI3K). However, it is known that emodin, which shows toxicity to cancer cells, may cause kidney toxicity, hepatotoxicity, and reproductive toxicity especially at high doses and long-term use. At the same time, studies of emodin, which has poor oral bioavailability, to transform this disadvantage into an advantage with nano-carrier systems reveal that natural compounds are not always directly usable compounds. Consequently, this review aimed to shed light on the anti-proliferative and anti-carcinogenic properties of emodin, as well as its potential toxicities and the advantages of drug delivery systems on bioavailability.

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“…The newest study revealed that emodin inhibits breast cancer lung metastasis [65]. Combinatorial therapy with emodin and thymoquinone was also efficient in attenuating migration of MCF-7 breast cancer cells, inducing apoptosis, inhibiting cell proliferation, while enhancing cytotoxicity [66].…”

Section: Angiogenesis and Metastasismentioning

confidence: 99%

The Health Benefits of Emodin, a Natural Anthraquinone Derived from Rhubarb—A Summary Update

Stompor-Gorący

2021

IJMS

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Emodin (6-methyl-1,3,8-trihydroxyanthraquinone) is a naturally occurring anthraquinone derivative found in roots and leaves of various plants, fungi and lichens. For a long time it has been used in traditional Chinese medicine as an active ingredient in herbs. Among other sources, it is isolated from the rhubarb Rheum palmatum or tuber fleece-flower Polygonam multiflorum. Emodin has a wide range of biological activities, including diuretic, antibacterial, antiulcer, anti-inflammatory, anticancer and antinociceptive. According to the most recent studies, emodin acts as an antimalarial and antiallergic agent, and can also reverse resistance to chemotherapy. In the present work the potential therapeutic role of emodin in treatment of inflammatory diseases, cancers and microbial infections is analysed.

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Combinatorial therapy of Thymoquinone and Emodin synergistically enhances apoptosis, attenuates cell migration and reduces stemness efficiently in breast cancer

Cited by 30 publications

References 32 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

Is Emodin with Anticancer Effects Completely Innocent? Two Sides of the Coin

The Health Benefits of Emodin, a Natural Anthraquinone Derived from Rhubarb—A Summary Update

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