Thymoquinone (TQ) regulates cyclooxygenase-2 expression and prostaglandin E2 production through PI3kinase (PI3K)/p38 kinase pathway in human breast cancer cell line, MDA-MB-231

Yu, Seon Mi; Kim, Song Ja

doi:10.1080/19768354.2011.647834

Cited by 11 publications

(6 citation statements)

References 20 publications

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“…Specifically, TQ in lower concentrations induced phosphorylation of Akt while higher concentrations inhibited p-Akt. TQ stimulatory effects on p-Akt were previously observed in MDA-MB-231 breast cancer cells ( Yu and Kim, 2012 ) while the inhibition of p-Akt by TQ was previously confirmed in various cancer models ( Koka et al, 2008 ; Yi et al, 2008 ; Arafa et al, 2011 ; Hussain et al, 2011 ; Rajput et al, 2013 ; Khan et al, 2019 ). The observed TQ hormetic effects where low concentration increased levels of p-NF-κB p65 in LAMA-84r cells and p-Akt in both LAMA-84 cell lines were probably due to compensatory mechanisms activated by cells.…”

Section: Discussionmentioning

confidence: 73%

Metformin and Thymoquinone Synergistically Inhibit Proliferation of Imatinib-Resistant Human Leukemic Cells

et al. 2022

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Chemotherapy resistance is one of the major challenges in cancer treatment, including leukemia. A massive array of research is evaluating combinations of drugs directed against different intracellular signaling molecules to overcome cancer resistance, increase therapy effectiveness, and decrease its adverse effects. Combining chemicals with proven safety profiles, such as drugs already used in therapy and active substances isolated from natural sources, could potentially have superior effects compared to monotherapies. In this study, we evaluated the effects of metformin and thymoquinone (TQ) as monotherapy and combinatorial treatments in chronic myeloid leukemia (CML) cell lines sensitive and resistant to imatinib therapy. The effects were also evaluated in primary monocytic acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) cells. Both compounds induced a dose- and time-dependent decrease of viability and proliferation in tested cells. Metformin had similar IC50 values in imatinib-sensitive and imatinib-resistant cell lines. IC50 values of TQ were significantly higher in imatinib-resistant cells, but with a limited resistance index (2.4). Synergistic effects of combinatorial treatments were observed in all tested cell lines, as well as in primary cells. The strongest synergistic effects were observed in the inhibition of imatinib-resistant cell line proliferation. Metformin and TQ inhibited the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling and induced apoptosis in tested cell lines and primary cells. The enhanced effects of combinatorial treatments on the induction of apoptosis were more dominant in imatinib-resistant compared to imatinib-sensitive CML cells. Primary cells were more sensitive to combinatorial treatments compared to cell lines. A combination of 1.25 mM metformin and 0.625 µM TQ increased the levels of cleaved poly (ADP-ribose) polymerase (PARP), decreased the levels of proliferation regulatory proteins, and inhibited protein kinase B (Akt) and NF-κB signaling in primary CLL cells. This study demonstrates that combinatorial treatments of imatinib-resistant malignant clones with metformin and TQ by complementary intracellular multi-targeting represents a promising approach in future studies.

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Section: Discussionmentioning

confidence: 73%

Metformin and Thymoquinone Synergistically Inhibit Proliferation of Imatinib-Resistant Human Leukemic Cells

et al. 2022

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“…The overexpression of COX2 plays a crucial role as prostaglandin up-regulates angiogenesis and increases the resistance to apoptosis (Costa et al, 2002 ; Santos and Costa-Pereira, 2011 ). COX2 is reported for the inhibition of some clinical behavior of tumors (Banerjee et al, 2009 ; Yu and Kim, 2012 ). The inhibitor of COX2 shows a significant effect on its inhibition, while it also possess some side effect on other tissues, therefore in recent years natural product received attention for its choice to prevent cancer through the COX2 inhibitory mechanism.…”

Section: Molecular Mechanisms Of Thymoquinonementioning

confidence: 99%

Therapeutic Potential and Pharmaceutical Development of Thymoquinone: A Multitargeted Molecule of Natural Origin

et al. 2017

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Thymoquinone, a monoterpene molecule is chemically known as 2-methyl-5-isopropyl-1, 4-benzoquinone. It is abundantly present in seeds of Nigella sativa L. that is popularly known as black cumin or black seed and belongs to the family Ranunculaceae. A large number of studies have revealed that thymoquinone is the major active constituent in N. sativa oil this constituent is responsible for the majority of the pharmacological properties. The beneficial organoprotective activities of thymoquinone in experimental animal models of different human diseases are attributed to the potent anti-oxidant and anti-inflammatory properties. Thymoquinone has also been shown to alter numerous molecular and signaling pathways in many inflammatory and degenerative diseases including cancer. Thymoquinone has been reported to possess potent lipophilicity and limited bioavailability and exhibits light and heat sensitivity. Altogether, these physiochemical properties encumber the successful formulation for the delivery of drug in oral dosages form and restrict the pharmaceutical development. In recent past, many efforts were undertaken to improve the bioavailability for clinical usage by manipulating the physiochemical parameters. The present review aimed to provide insights regarding the physicochemical characteristics, pharmacokinetics and the methods to promote pharmaceutical development and endorse the clinical usage of TQ in future by overcoming the associated physiochemical obstacles. It also enumerates briefly the pharmacological and molecular targets of thymoquinone as well as the pharmacological properties in various diseases and the underlying molecular mechanism. Though, a convincing number of experimental studies are available but human studies are not available with thymoquinone despite of the long history of use of black cumin in different diseases. Thus, the clinical studies including pharmacokinetic studies and regulatory toxicity studies are required to encourage the clinical development of thymoquinone.

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“…The overexpression of COX2 plays a vital role in the upregulation of angiogenesis by prostaglandin and also shows effect in apoptosis by increasing the resistance to apoptosis [ 91 ]. COX2 also shows the inhibition of clinical behavior of some tumors [ 92 ]. However, COX2 inhibition is a critical step in the prevention of cancer.…”

Section: The Implications Of N Sativa In Cancementioning

confidence: 99%

Therapeutic Implications of Black Seed and Its Constituent Thymoquinone in the Prevention of Cancer through Inactivation and Activation of Molecular Pathways

Rahmani

Alzohairy

Khan

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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The cancer is probably the most dreaded disease in both men and women and also major health problem worldwide. Despite its high prevalence, the exact molecular mechanisms of the development and progression are not fully understood. The current chemotherapy/radiotherapy regime used to treat cancer shows adverse side effect and may alter gene functions. Natural products are generally safe, effective, and less expensive substitutes of anticancer chemotherapeutics. Based on previous studies of their potential therapeutic uses, Nigella sativa and its constituents may be proved as good therapeutic options in the prevention of cancer. Black seeds are used as staple food in the Middle Eastern Countries for thousands of years and also in the treatment of diseases. Earlier studies have shown that N. sativa and its constituent thymoquinone (TQ) have important roles in the prevention and treatment of cancer by modulating cell signaling pathways. In this review, we summarize the role of N. sativa and its constituents TQ in the prevention of cancer through the activation or inactivation of molecular cell signaling pathways.

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Thymoquinone (TQ) regulates cyclooxygenase-2 expression and prostaglandin E2 production through PI3kinase (PI3K)/p38 kinase pathway in human breast cancer cell line, MDA-MB-231

Cited by 11 publications

References 20 publications

Metformin and Thymoquinone Synergistically Inhibit Proliferation of Imatinib-Resistant Human Leukemic Cells

Metformin and Thymoquinone Synergistically Inhibit Proliferation of Imatinib-Resistant Human Leukemic Cells

Therapeutic Potential and Pharmaceutical Development of Thymoquinone: A Multitargeted Molecule of Natural Origin

Therapeutic Implications of Black Seed and Its Constituent Thymoquinone in the Prevention of Cancer through Inactivation and Activation of Molecular Pathways

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