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| Cancer models or effects of anticancer agents | Intervention (s) | Findings (Mechanisms) | References |
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| In vitro studies | Doxorubicin-resistant
human breast cancer cells line (MCF-7/DOX cells) | TQ (25, 50 or 100 µM) for 48 hours & NSO Nano emulsion | (i) Concentration dependent growth inhibition
(ii) Induce apoptosis, p53 protein
(iii) Upregulation of PTEN (inhibit PI3K/Akt pathway) | [124, 125] |
Human cervical squamous
cancer cells | TQ (1.0 to 30 μg/mL) for 24, 48 and 72 hours | (i) More cytotoxic than cisplatin towards this cancerous cell (but less cytotoxicity towards normal cells)
(ii) Downregulates Bcl-2 protein | [126] |
Myeloblastic leukemia
(HL-60 cells) | TQ | (i) Induces apoptosis, disrupts mitochondrial membrane potential, triggers the activation of caspases 3, 8 & 9 in HL-60 cells | [127] |
| Human bladder cancer cells (T24 and 253J) | TQ (20-160 µmol/L) for different periods (24h, 48h, and 72h) | (i) TQ showed marked cytotoxicity on bladder cancer cells
(ii) It inhibited cancerous cells rapid multiplication and evoked apoptosis via activation of caspase.
(iii) TQ also resulted in activation of ER stress, mitochondrial disturbance and enhanced mitochondrial mediated apoptotic path. | [128] |
| Renal cell cancer (RCC) cell lines (786-O and ACHN) | TQ (40 μmol/L) for 24 hours | (i) TQ suppressed migration, invasion and epithelial-mesenchymal transition in RCC cells.
(ii) TQ exhibited significant inhibition of the metastasis of RCC cells through induction of autophagy via AMPK/mTOR signalling. | [129] |
| Human renal tubular epithelial cell (HK2) and the human RCC cell lines (769-P & 786-O) | TQ (0.5, 1, 2.5, 5, 10, 15 & 20 µM) at various durations (0, 24, 48 & 72 h). | (i) TQ markedly inhibited the migration and invasion of the human RCC 769-P and 786-O cell lines.
(ii) TQ also increased the expression of E-cadherin and reduced the expression of Snail, ZEB1 and vimentin at the mRNA as well as protein levels in dose-dependent fashion.
(iii) As a result, the extents of phosphorylation of hepatic kinase B1 and AMPK were upregulated. | [130] |
| Human prostate cancer cell lines (DU145 and C3) | TQ (2.5, 5.0 & 10 µM) for 24 hours. | (i) TQ substantially arrested the proliferation of prostate cancer.
(ii) It inhibited the migrating and invading capability of prostate cancer DU145 and PC3 cells.
(iii) TQ also downregulated the expression of TGF-β, Smad2 and Smad3 in prostate cancer cells. | [131] |
| Hepatocellular cancer cell line (HepG2) | TQ (3–24 µM) for 24 hours. | (i) Decreased both the no. of viable HepG2 cells and the levels
(ii) TQ induced cell cycle arrest and apoptosis
(iii) Increased total antioxidant status (dose dependently)
(iv) TQ reduced the release of VEGF of HepG2 cells | [132] |
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| In vivo studies | Diethyl nitrosamine inducedhepatocarcinogenesis in Wistar rats | Ethanolic extract of NS (250 mg/kg) for 5 consecutive days. | (i) The chemical induced increment of liver weight, hepato-somatic indices, serum AFP and VEGF levels, and hepatic HGFβ protein expression were significantly reversed by the extract.
(ii) The histopathological alteration of the livers due to the chemical was decreased in NS extract received rats without harmful effects. | [133] |
| Orthotopic model inmice [triple-negative breast cancer (TNBC) cell lines] | TQ (20 or 100 mg/k) once every 3 days | (i) TQ markedly reduced the growth of MDA-MB-231 tumor.
(ii) TQ decreased TNBC cell viability and proliferation as well as the migration and invasion of TNBC cells.
(iii) TQ also downregulated the expression of eEF-2K (via modulation of the NF-κB/miR-603), Src/FAK, and Akt in TNBC cells. | [134] |
| Colon carcinogenesis of rats model | NSO for 14 weeks | (i) NSO revealed a significant antiproliferative activity in both initiation and post-initiation phases
(ii) Inhibited colon carcinogenesis of rats mainly in the post-initiation stage with no evident of adverse effects | [135] |
| Mouse model of colorectal carcinogenesis & C26 cell | TQ (5 mg/kg) for 3 weeks & TQ (0, 20, 40, 60 μM) in vitro | (i) TQ reduced tumor multiplicity
(ii) TQ impeded tumor growth and induce apoptosis in HCT116 xenografts
(iii) Sub-cytotoxic conc. of TQ (40μM) also reduced C26 cell invasion
(iv) Anti-neoplastic and pro-apoptotic p53-dependent mechanism | [136] |
Rat multi-organ
carcinogenesis | NSO for 30 weeks | (i) Reduction in malignant and benign colon tumor sizes, tumors in the lungs and in diverse parts of the alimentary canal principally the oesophagus and fore stomach | [137] |
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| Effect on anti-cancer drugs | Cyclophosphamide
Induced toxicity (abnormal RF & LFT and reduced Hgb) in rat | NSO (1ml/kg) and TQ (10 mg/kg) EOD for 12 days | (i) Substantial reduction in overall cyclophosphamide induced toxicity in both NSO and TQ treated groups. | [138] |
| Antitumor Effect of TQ and gemcitabine on xenograft mouse and PANC-1, AsPC-1 and BxPC-3 cell lines of pancreatic cancer models, | TQ (0–50 µmol/L) & 1.0 mg/ mouse daily
| (i) TQ pre-treatment synergistically increased the gemcitabine actions of apoptotic and tumor growth inhibition of pancreatic cancer cells.
(ii) Concomitant uses resulted in the change of several molecular signaling, including the downregulation of Notch1, NICD associated with up-regulation of PTEN, via the inactivation of Akt/mTOR/S6 signaling.
(iii) TQ and gemcitabine also induced suppression of anti-apoptotic Bcl-2, Bcl-xL, XIAP and overexpression and activation Caspase-3, Caspase-9, & Bax. | [139] |
| Cytotoxicity assay of TQ and paclitaxel on mouse breast cancer cell line (4T1) and animal models | TQ (6.25, 12.5, 25, 50, & 100 μM) for 24 & 48 hours; (0.64, 2.4 & 3.2 mg/kg of mouse body weight). | (i) TQ induced marked cytotoxicity and apoptosis, while inhibiting wound healing and migration of 4T1 cells.
(ii) Co-administration of TQ and paclitaxel significantly induced cytotoxicity and apoptosis compared to separate administration.
(iii) The combination of paclitaxel and the lower dose TQ markedly inhibited the tumor growth.
(iv) Both agents also modulated the apoptosis genes, p53 and JAK-STAT signaling, while overexpressing the levels of Caspase-3, Caspase-7, and Caspase-12. | [140] |
| Anti-tumor activity of TQ and topotecan in colorectal cancer cell line (HT-29) | TQ (40, 55 & 60 µM)
| (i) TQ significantly enhanced the anti-tumor effect of non-cytotoxic dose of topotecan.
(ii) Both drugs induced apoptosis via a p53-independent mechanism, while the expression of p21 was only noted in TQ therapy.
(iii) TQ improved the effectiveness of topotecan by inhibiting proliferationand lowering toxicity via p53- and Bax/Bcl2-independent mechanisms. | [141] |
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