Metastasized lung cancer suppression by Morinda citrifolia (Noni) leaf compared to Erlotinib via anti-inflammatory, endogenous antioxidant responses and apoptotic gene activation.
Metastasized lung and liver cancers cause over 2 million deaths annually, and are amongst the top killer cancers worldwide. Morinda citrifolia (Noni) leaves are traditionally consumed as vegetables in the tropics. The macro and micro effects of M. citrifolia (Noni) leaves on metastasized lung cancer development in vitro and in vivo were compared with the FDA-approved anti-cancer drug Erlotinib. The extract inhibited the proliferation and induced apoptosis in A549 cells (IC50 = 23.47 μg/mL) and mouse Lewis (LL2) lung carcinoma cells (IC50 = 5.50 μg/mL) in vitro, arrested cancer cell cycle at G0/G1 phases and significantly increased caspase-3/-8 without changing caspase-9 levels. The extract showed no toxicity on normal MRC5 lung cells. Non-small-cell lung cancer (NSCLC) A549-induced BALB/c mice were fed with 150 and 300 mg/kg M. citrifolia leaf extract and compared with Erlotinib (50 mg/kg body weight) for 21 days. It significantly increased the pro-apoptotic TRP53 genes, downregulated the pro-tumourigenesis genes (BIRC5, JAK2/STAT3/STAT5A) in the mice tumours, significantly increased the anti-inflammatory IL4, IL10 and NR3C1 expression in the metastasized lung and hepatic cancer tissues and enhanced the NFE2L2-dependent antioxidant responses against oxidative injuries. The extract elevated serum neutrophils and reduced the red blood cells, haemoglobin, corpuscular volume and cell haemoglobin concentration in the lung cancer-induced mammal. It suppressed inflammation and oedema, and upregulated the endogenous antioxidant responses and apoptotic genes to suppress the cancer. The 300 mg/kg extract was more effective than the 50 mg/kg Erlotinib for most of the parameters measured.
UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Level 4, 43400, Serdang, Selangor, Malaysia.
Swee-Ling
SL
Lim
Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
Noordin M
NM
Mustapha
Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
Yong-Meng
YM
Goh
UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Level 4, 43400, Serdang, Selangor, Malaysia.
Nurul Ain Abu
NA
Bakar
UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Level 4, 43400, Serdang, Selangor, Malaysia. mohamed.suhaila@gmail.com.
Suhaila
http://orcid.org/0000-0002-2954-3821
S
Mohamed
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D000069347:Erlotinib Hydrochloride / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D032066:Morinda / Q000737:chemistry*; D009362:Neoplasm Metastasis; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D010936:Plant Extracts; D000069347:Erlotinib Hydrochloride
BCL2; Differential counts; IL10; IL4; NFE2L2; NR3C1; TRP53