Enhancement of apoptotic activities on brain cancer cells via the combination of γ-tocotrienol and jerantinine A

Abubakar, Ibrahim Babangida; Lim, Kuan‐Hon; Kam, Toh‐Seok; Loh, Hwei‐San

doi:10.1016/j.phymed.2017.03.004

Cited by 23 publications

(28 citation statements)

References 27 publications

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“…This conforms to a recent study that demonstrated the cytotoxic potency of combined low-concentration treatment of γ-tocotrienol and jerantinine A, which was also able to activate caspase 8, 9 and 3 enzymatic activities and disrupt microtubules in a different cell type, i.e. brain cancer (6). This suggests that the combination of different isomers of tocotrienol such as γ and δ with jerantinine derivatives might induce synergistic apoptotic effects against a broad spectrum of cancer cell lines.…”

Section: Discussionsupporting

confidence: 91%

“…In contrast, unlike the single-compound treatments of δ-tocotrienol and jerantinine A, the combined treatment demonstrated more than 2-fold selective toxicity on A549 cells thereby minimizing toxicity on normal MRC5 cells. Indeed, the study herein conformed to previous suggestion that combined therapy could potentially minimize non-selective toxicity and improve potency of phytochemicals (6).…”

Section: Discussionsupporting

confidence: 86%

“…Combined therapy of phytochemicals has been suggested as an alternative to potentially overcome the abovementioned limitations. In fact, the potency of tocotrienols could be improved via the combined therapy even though a much lower concentration is used (6). Therefore, the present study investigated the cytotoxic and apoptotic effects of δ-tocotrienol and jerantinine A which were combined at sub-effective concentrations aiming at improving the therapeutic potency and minimizing the non-selective toxicity towards the normal healthy cells.…”

Section: Introductionmentioning

confidence: 99%

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Potentiation of in vitro apoptotic effects of δ-Tocotrienol and Jerantinine A on human lung adenocarcinoma cells

Abubakar

Loh

2019

J Herbmed Pharmacol

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Introduction: The apoptotic effects of single-compound and combined sub-effective concentrations of δ-tocotrienol and jerantinine A on human lung adenocarcinoma (A549) cells were investigated. Methods: Assays including cell viability, histochemical and immunofluorescence staining techniques, flow cytometry and enzyme activity were used. Results: The combination of δ-tocotrienol with jerantinine A at sub-effective concentrations induced a synergistic effect and improved selective toxicity towards cancerous A549 cells over normal lung fibroblast (MRC5) cells compared to the single-compound jerantinine. Morphological features of apoptosis were evident on treated A549 cells. Combined sub-effective concentrations of δ-tocotrienol with jerantinine A induced a predominantly G2/M cell cycle arrest and characterised by a disruption of microtubular networks mediated via caspase 8, 9 and 3 enzymatic activities. Conclusion: These findings demonstrated improved potency in vitro and reduced dose-related toxicity of jerantinine A to normal cells through prospective combined treatment between low-concentration δ-tocotrienol and jerantinine A for lung cancer.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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Potentiation of in vitro apoptotic effects of δ-Tocotrienol and Jerantinine A on human lung adenocarcinoma cells

Abubakar

Loh

2019

J Herbmed Pharmacol

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“…Accumulating evidence suggests that many dietary factors like antioxidants (polyphenols) are used alone or in combination with traditional/conventional chemotherapy to prevent or treat cancer [26][27][28][29][30][31][32][33][34][35]. Crude and processed plant extracts are studied extensively to evaluate its role in treatment as chemopreventive drug or to use in combination that can synergistically improve the outcome of current chemotherapy and lower the toxicity [36][37][38].…”

Section: Discussionmentioning

confidence: 99%

Correlation of Antioxidant and Antiproliferative Activity of Amla and Ginger

Kulsum¹,

Suresh²,

Mehta

2018

Asian J Pharm Clin Res

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Objective: Our study focused on evaluating the anticancer property of ascorbic acid and aqueous extract of amla and ginger.Methods: Antioxidant capacity of ascorbic acid, aqueous extract of amla, and ginger was obtained by 2,2-diphenyl-1-picrylhydrazyl method and total antioxidant capacity (TAC). Vero cell line, PA-1, Cal-27, Cal-27 CisR, and DysMSCTR16 cell lines were treated with antioxidants to evaluate its antiproliferative property using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Colony and spheroid formation assays were also carried out in the presence of extracts to assess its role in anticancer stem cell activity.Results: Two volumes of amla 5 µl (~0.016 g) and 25 µl (~0.08 g) and ginger 5 µl (~0.02 g) and 25 µl (~0.1 g) showed TAC activity equivalent to 0.25 mM and 2 mM ascorbic acid, respectively. Amla and ascorbic acid showed significant antiproliferative property in normal (Vero) p=0.05, cancer (PA-1, Cal-27) p=0.005, and resistant (Cal-27 CisR) p=0.05 cell lines and ginger extract in Vero and Cal-27 cell lines (p=0.05). In PA-1 and Cal-27 CisR cell line, ginger extract showed proliferative activity (p=0.005). Antioxidants showed no antiproliferative activity in DysMSCTR16 cells. Amla extract and ascorbic acid showed significant inhibitory effect on spheroid (p=0.005) and colony formation capacity (p=0.0005) among dysplastic, cancer, and resistant cell lines. Ginger showed inhibitory effect (p=0.05) only in colony formation capacity. Conclusion:Overall, we found a strong correlation between antioxidant and antiproliferative activity of ascorbic acid, amla, and ginger. Amla and ascorbic acid proved to be effective in controlling cell proliferation and self-renewal properties of cancer cells. However, ginger was found to have selective and less antiproliferative effect in comparison to amla.

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“…Previous studies have shown that GTT has an effective antitumor activity compared to other tocotrienol isomers [12]. GTT as an anticancer agent is selective on malignant cells, is capable of targeting multiple signaling pathways simultaneously, and has a synergistic effect with chemotherapy [13,14]. Hence, various studies have been done to identify GTT capabilities and its mechanism in anticancer activities.…”

Section: Introductionmentioning

confidence: 99%

Silencing of Peroxiredoxin-4 in Anticancer Activity of Gamma-Tocotrienol

Aznan¹,

Jubri²

2020

Synthetic Biology - New Interdisciplinary Science

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Peroxiredoxin-4 (PRDX4) is known to have a role in protecting cells from oxidative stress. It has been previously reported to increase in HepG2 liver cancer cells treated with gamma-tocotrienol (GTT). As GTT treatment potentially kills the cancer cell by regulating multiple signaling pathways, this study aims to determine the involvement of PRDX4 in GTT anticancer activity by silencing the PRDX4 gene. The efficiency of PRDX4 silencing is achieved by optimizing HepG2 cell density, effect of serum presence in transduction media, incubation time of the cells with lentivirus, polybrene concentration, puromycin dose, functional titer, and multiplicity of infection (MOI) of the lentivirus. Silenced HepG2-PRDX4 cells (HepG2-shRNA-PRDX4) were treated with 70 μM of GTT for 48 h. GTT treatment significantly decreased the HepG2-shRNA-PRDX4 cell viability, increased apoptosis rate, and reduced free radical production compared to untreated HepG2-shRNA-PRDX4 cells. These findings are further supported by proteomic analysis, which showed that pro-apoptotic and DNA damage proteins were upregulated, and proteins involved in cell cycle arrest, carcinogenesis, and anti-apoptotic signaling pathways were downregulated in HepG2-shRNA-PRDX4 cells treated with GTT compared to control. In conclusion, PRDX4 plays a role in GTT anticancer activity by increasing free radical production and oxidative damage to induce apoptosis in HepG2 cell.

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Enhancement of apoptotic activities on brain cancer cells via the combination of γ-tocotrienol and jerantinine A

Cited by 23 publications

References 27 publications

Potentiation of in vitro apoptotic effects of δ-Tocotrienol and Jerantinine A on human lung adenocarcinoma cells

Potentiation of in vitro apoptotic effects of δ-Tocotrienol and Jerantinine A on human lung adenocarcinoma cells

Correlation of Antioxidant and Antiproliferative Activity of Amla and Ginger

Silencing of Peroxiredoxin-4 in Anticancer Activity of Gamma-Tocotrienol

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