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Anti-cancer effects of Ajwa dates (Phoenix dactylifera L.) in diethylnitrosamine induced hepatocellular carcinoma in Wistar rats.
BMC Complement Altern Med 2017; 17(1):418BC

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) accounts for major cancer-related deaths despite current advanced therapies. Treatment and prognosis of HCC is better in patients with preserved liver function. Many natural products including ajwa dates (Phoenix dactylifera L.), are claimed to have hepatoprotective and HCC inhibitory effects, but most lack scientific validation. To prove our hypothesis, we attempted to evaluate the HCC inhibitory effects, and other beneficial properties of the aqueous extract of ajwa dates (ADE) in a rat model of diethylnitrosamine (DEN) induced liver cancer.

METHODS

Thirty-two male rats were divided into four groups of eight each as follows, Group A: untreated control; Group B: DEN control (180 mg/kg bw), Group C: DEN + ADE 0.5 g/kg bw; and Group D: DEN +1.0 g/kg bw. Rats from all groups were assessed for liver cancer progression or inhibition by evaluating histological, biochemical, antioxidant enzyme status, cytokines and gene expression profiles.

RESULTS

DEN treatment Groups (B, C, D) showed histological features of HCC and in rats treated with ADE (Groups C, D) partial to complete reversal of normal liver architecture was observed. Antioxidant enzymes such as superoxide dismutase (SOD), glutathione reductase (GR), glutatione peroxidase (GPx) and catalase (CAT) were increased, while the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels and lipid peroxidation were significantly decreased in Group C and Group D compared to Group B. Pro-inflammatory cytokines such as interleukin (IL)-1α, IL-1β,, GM-CSF) were increased in the serum of rats in Group B while the anti-tumor cytokines (IL-2, IL-12) were increased in ADE treated Groups (C, D). In addition, Alpha-Feto Protein (AFP) and IL-6 gene expression levels were upregulated in Group B, while they were significantly downregulated in ADE treated Groups (C, D).

CONCLUSIONS

ADE helped in the reversal of DEN damaged liver towards normal. Restoration of anti-oxidant enzymes, liver enzymes, cytokines balance and gene expression to normal levels following ADE treatment indicates that ADE improves liver function and inhibits HCC. ADE can, therefore, be used together with conventional therapeutics for HCC.

Authors+Show Affiliations

Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia. Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University (KAU), PO BOX 80216, Jeddah, 21589, Kingdom of Saudi Arabia.Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University (KAU), PO BOX 80216, Jeddah, 21589, Kingdom of Saudi Arabia. kgauthaman@kau.edu.sa.Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University (KAU), PO BOX 80216, Jeddah, 21589, Kingdom of Saudi Arabia.Center of Innovation in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.Center of Innovation in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia. King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia. Department of Agriculture, Faculty of Agricultural and Food Sciences, American University of Beirut (AUB), Beirut, Lebanon.Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University (KAU), PO BOX 80216, Jeddah, 21589, Kingdom of Saudi Arabia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28830415

Citation

Khan, Fazal, et al. "Anti-cancer Effects of Ajwa Dates (Phoenix Dactylifera L.) in Diethylnitrosamine Induced Hepatocellular Carcinoma in Wistar Rats." BMC Complementary and Alternative Medicine, vol. 17, no. 1, 2017, p. 418.
Khan F, Khan TJ, Kalamegam G, et al. Anti-cancer effects of Ajwa dates (Phoenix dactylifera L.) in diethylnitrosamine induced hepatocellular carcinoma in Wistar rats. BMC Complement Altern Med. 2017;17(1):418.
Khan, F., Khan, T. J., Kalamegam, G., Pushparaj, P. N., Chaudhary, A., Abuzenadah, A., ... Al-Qahtani, M. (2017). Anti-cancer effects of Ajwa dates (Phoenix dactylifera L.) in diethylnitrosamine induced hepatocellular carcinoma in Wistar rats. BMC Complementary and Alternative Medicine, 17(1), p. 418. doi:10.1186/s12906-017-1926-6.
Khan F, et al. Anti-cancer Effects of Ajwa Dates (Phoenix Dactylifera L.) in Diethylnitrosamine Induced Hepatocellular Carcinoma in Wistar Rats. BMC Complement Altern Med. 2017 Aug 22;17(1):418. PubMed PMID: 28830415.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-cancer effects of Ajwa dates (Phoenix dactylifera L.) in diethylnitrosamine induced hepatocellular carcinoma in Wistar rats. AU - Khan,Fazal, AU - Khan,Tariq Jamal, AU - Kalamegam,Gauthaman, AU - Pushparaj,Peter Natesan, AU - Chaudhary,Adeel, AU - Abuzenadah,Adel, AU - Kumosani,Taha, AU - Barbour,Elie, AU - Al-Qahtani,Mohammed, Y1 - 2017/08/22/ PY - 2017/04/07/received PY - 2017/08/14/accepted PY - 2017/8/24/entrez PY - 2017/8/24/pubmed PY - 2017/9/12/medline KW - Ajwa date extract KW - Anti-oxidants KW - Cytokines KW - Hepatocellular carcinoma KW - In vivo KW - Quantitative real-time PCR SP - 418 EP - 418 JF - BMC complementary and alternative medicine JO - BMC Complement Altern Med VL - 17 IS - 1 N2 - BACKGROUND: Hepatocellular carcinoma (HCC) accounts for major cancer-related deaths despite current advanced therapies. Treatment and prognosis of HCC is better in patients with preserved liver function. Many natural products including ajwa dates (Phoenix dactylifera L.), are claimed to have hepatoprotective and HCC inhibitory effects, but most lack scientific validation. To prove our hypothesis, we attempted to evaluate the HCC inhibitory effects, and other beneficial properties of the aqueous extract of ajwa dates (ADE) in a rat model of diethylnitrosamine (DEN) induced liver cancer. METHODS: Thirty-two male rats were divided into four groups of eight each as follows, Group A: untreated control; Group B: DEN control (180 mg/kg bw), Group C: DEN + ADE 0.5 g/kg bw; and Group D: DEN +1.0 g/kg bw. Rats from all groups were assessed for liver cancer progression or inhibition by evaluating histological, biochemical, antioxidant enzyme status, cytokines and gene expression profiles. RESULTS: DEN treatment Groups (B, C, D) showed histological features of HCC and in rats treated with ADE (Groups C, D) partial to complete reversal of normal liver architecture was observed. Antioxidant enzymes such as superoxide dismutase (SOD), glutathione reductase (GR), glutatione peroxidase (GPx) and catalase (CAT) were increased, while the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels and lipid peroxidation were significantly decreased in Group C and Group D compared to Group B. Pro-inflammatory cytokines such as interleukin (IL)-1α, IL-1β,, GM-CSF) were increased in the serum of rats in Group B while the anti-tumor cytokines (IL-2, IL-12) were increased in ADE treated Groups (C, D). In addition, Alpha-Feto Protein (AFP) and IL-6 gene expression levels were upregulated in Group B, while they were significantly downregulated in ADE treated Groups (C, D). CONCLUSIONS: ADE helped in the reversal of DEN damaged liver towards normal. Restoration of anti-oxidant enzymes, liver enzymes, cytokines balance and gene expression to normal levels following ADE treatment indicates that ADE improves liver function and inhibits HCC. ADE can, therefore, be used together with conventional therapeutics for HCC. SN - 1472-6882 UR - https://www.unboundmedicine.com/medline/citation/28830415/Anti_cancer_effects_of_Ajwa_dates__Phoenix_dactylifera_L___in_diethylnitrosamine_induced_hepatocellular_carcinoma_in_Wistar_rats_ L2 - https://bmccomplementalternmed.biomedcentral.com/articles/10.1186/s12906-017-1926-6 DB - PRIME DP - Unbound Medicine ER -