Thymoquinone inhibits cell proliferation through regulation of G1/S phase cell cycle transition in N-nitrosodiethylamine-induced experimental rat hepatocellular carcinoma

Raghunandhakumar, Subramanian; Paramasivam, Arumugam; Senthilraja, S.; Naveenkumar, Chandrashekar; Asokkumar, Selvamani; Binuclara, John; Jagan, Sundaram; Anandakumar, Pandi; Devaki, Thiruvengadam

doi:10.1016/j.toxlet.2013.08.018

Cited by 71 publications

(58 citation statements)

References 46 publications

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“…Thymoquinone had a potent anti-proliferative activity by regulating the G 1 /S phase cell cycle transition and exhibited a beneficial role in the treatment of hepatocellular carcinogenesis [101,102]. Moreover, thymoquinone inhibited the growth of human cholangiocarcinoma cell lines, induced cell cycle arrest, and promoted apoptosis.…”

Section: Nigella Sativa and Thymoquinonementioning

confidence: 99%

Spices for Prevention and Treatment of Cancers

et al. 2016

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Spices have been widely used as food flavorings and folk medicines for thousands of years. Numerous studies have documented the antioxidant, anti-inflammatory and immunomodulatory effects of spices, which might be related to prevention and treatment of several cancers, including lung, liver, breast, stomach, colorectum, cervix, and prostate cancers. Several spices are potential sources for prevention and treatment of cancers, such as Curcuma longa (tumeric), Nigella sativa (black cumin), Zingiber officinale (ginger), Allium sativum (garlic), Crocus sativus (saffron), Piper nigrum (black pepper) and Capsicum annum (chili pepper), which contained several important bioactive compounds, such as curcumin, thymoquinone, piperine and capsaicin. The main mechanisms of action include inducing apoptosis, inhibiting proliferation, migration and invasion of tumors, and sensitizing tumors to radiotherapy and chemotherapy. This review summarized recent studies on some spices for prevention and treatment of cancers, and special attention was paid to bioactive components and mechanisms of action.

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Section: Nigella Sativa and Thymoquinonementioning

confidence: 99%

Spices for Prevention and Treatment of Cancers

et al. 2016

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“…The key liver enzymes namely, such as aspartate amino- transferase, alanine aminotransaminase, alkaline phosphatase, and lactate dehydrogenase exhibited reduced activity and the average number of hepatic nodules in rats treated with N-nitrosodiethylamine (NDEA) was decreased after both pre- and post-treatment with TQ. The expression of several cell proliferation markers, such as cyclin D1, cyclin E, proliferating cell nuclear antigen (PCNA), and Ki67 was also declined (Raghunandhakumar et al, 2013). A considerable decrease in the incidence and multiplicity of forestomach tumors and fibrosarcoma development in Swiss albino mice followed by treatment with benzo[α]pyrene (B[α]P) and 20-methylcholanthrene, respectively, was reported after addition of TQ in drinking water (Badary et al, 1999; Badary and Gamal El-Din, 2001).…”

Section: Chemo-potentiating Role Of Tqmentioning

confidence: 99%

Thymoquinone as a Potential Adjuvant Therapy for Cancer Treatment: Evidence from Preclinical Studies

et al. 2017

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Thymoquinone (TQ), the main bioactive component of Nigella sativa, has been found to exhibit anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Moreover, TQ can specifically sensitize tumor cells toward conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy) and simultaneously minimize therapy-associated toxic effects in normal cells. In this review, we summarized the adjuvant potential of TQ as observed in various in vitro and in vivo animal models and discussed the pharmacological properties of TQ to rationalize its supplementary role in potentiating the efficacy of standard therapeutic modalities namely surgery, radiotherapy, chemotherapy, and immunotherapy. Altogether, we suggest further comprehensive evaluation of TQ in preclinical and clinical levels to delineate its implied utility as a novel complementary adjuvant therapy for cancer treatment.

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“…Liver, the major organ which metabolizes ingested material, thus is more susceptible to carcinogenic insult. N-Nitrosodiethylamine (NDEA) is widespread in tobacco smoke, beverages, agricultural chemicals, and industrial pollution, which are the important risk factors of hepatic disorders [8]. The NDEA-induced hepatocarcinogenicity is a common screening model to evaluate the hepatoprotective compound with antioxidant properties.…”

Section: Introductionmentioning

confidence: 99%

Antihepatocarcinoma Effect of Portulaca oleracea L. in Mice by PI3K/Akt/mTOR and Nrf2/HO‐1/NF‐κB Pathway

Zheng

Peng

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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The purpose of the present study was to evaluate the pharmacological effects of Portulaca oleracea L. (Purslane) (PL) on N-nitrosodiethylamine- (NDEA-) induced hepatocellular carcinomas (HCC) and explore its potential mechanism. Mice were randomly assigned to four groups: control group, NDEA group, NDEA + Purslane (100 mg/kg) group, and NDEA + Purslane (200 mg/kg) group. The animal of each group was given NDEA (100 ppm) in drinking water. 1 h later, Purslane dissolved in PBS was intragastrically administered for continuous seven days. The results showed that Purslane reduced the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in liver and serum. Purslane also reduced the contents of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), and methane dicarboxylic aldehyde (MDA) and restored the activity of superoxygen dehydrogenises (SOD) in serum. Purslane could obviously attenuate the hepatic pathological alteration. Furthermore, treatment with Purslane effectively inhibited the phosphorylations of phosphatidylinositol 3 kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), nuclear factor-kappa B (NF-κB), and inhibitor of NF-κBα (IκBα) and upregulated the expressions of NF-E2-related factor 2 (Nrf2) and heme oxygenase- (HO-) 1. In conclusion, our research suggested that Purslane exhibited protective effects on NDEA-induced hepatocellular carcinomas by anti-inflammatory and antioxidative properties via the PI3K/Akt/mTOR and Nrf2/HO-1/NF-κB pathway.

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Thymoquinone inhibits cell proliferation through regulation of G1/S phase cell cycle transition in N-nitrosodiethylamine-induced experimental rat hepatocellular carcinoma

Cited by 71 publications

References 46 publications

Spices for Prevention and Treatment of Cancers

Spices for Prevention and Treatment of Cancers

Thymoquinone as a Potential Adjuvant Therapy for Cancer Treatment: Evidence from Preclinical Studies

Antihepatocarcinoma Effect of Portulaca oleracea L. in Mice by PI3K/Akt/mTOR and Nrf2/HO‐1/NF‐κB Pathway

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