The therapeutic effects of nicotinamide in hepatocellular carcinoma through blocking IGF-1 and effecting the balance between Nrf2 and PKB

Al‐Gayyar, Mohammed M.H.; Bagalagel, Alaa; Noor, Adeeb; Almasri, Diena M.; Diri, Reem

doi:10.1016/j.biopha.2019.108653

Cited by 18 publications

(21 citation statements)

References 46 publications

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“…In fact, the NAM-induced activation of the p53/p21 pathway has exhibited antitumor properties in breast cancer, lymphoma, leukemia, and HCC [77,122,133,134]. Besides inhibiting SIRT1 and PARP1, NAM has shown to inhibit the oncogenic KRAS/AKT pathway in skin and pancreatic cancers [58,130], modulate the expression of Myc oncogene in bladder cancer [74], and suppress IGF-1 in HCC [78]. Despite the aforementioned evidence, more studies are needed to unravel NAM's entire molecular mechanism in diverse cancer scenarios, before its widespread implementation into clinical practice.…”

Section: Discussionmentioning

confidence: 99%

“…It also suppressed lung tumor formation in benzo(a)pyrene-exposed animal models, either when administered alone or synergistically with the glucocorticoid budesonide [75], in addition to urethane-exposed animal models [76]. Likewise, NAM suppressed liver tumor development in thioacetamide-exposed [78] or the formation of pre-neoplastic lesions in DEN (diethylnitrosamine)-exposed animal models, showing it plays a role in the early stages of cancer development [77]. In addition, oral NAM reduced the incidence of non-lymphocytic leukemia in alkylation-exposed animals [79].…”

Section: Skinmentioning

confidence: 97%

“…Dietary NAM suppressed lung tumor formation in urethane-exposed animal models [76] Liver Animal models NAM inhibited the formation of pre-neoplastic lesions [77] Cell lines, animal models NAM suppressed liver tumor formation in thioacetamide-exposed animal models [78] Leukemia Animal models Oral NAM reduced the incidence of non-lymphocytic leukemia in alkylation-exposed animal models [79] Kidney Animal models NAM suppressed tumor formation in streptozotocin-exposed animal models [80] DMBA NMSC is the most commonly diagnosed malignancy in Australia/New Zealand and North America, with a global estimated number of 1,042,056 new cases for 2018. Yet, it is characteristically absent from the top ten list of the estimated number of deaths in the same year [81].…”

Section: Skinmentioning

confidence: 99%

“…Cell lines NAM suppressed proliferation, while it enhanced apoptosis and cell cycle arrest of HCC in vitro [77] Cell lines, animal models NAM suppressed HCC growth, reduced serum AFP, and enhanced survival of thioacetamide-exposed animal models [78] Liver Most studies were found to involve the breast. An earlier study showed that intraperitoneal NAM suppressed breast cancer volume in animal models [119].…”

Section: Breastmentioning

confidence: 99%

“…Concerning liver-related primary cancers, NAM suppressed proliferation and enhanced apoptosis of HCC (hepatocellular carcinoma) in vitro mainly through stimulating the p53/p21 pathway [77]. Additionally, it reduced HCC growth, serum AFP (A-fetoprotein), and enhanced survival of thioacetamide-exposed animal models via suppressing IGF-1 (insulin-like growth factor 1), a well-known HCC promoter [78]. Similarly, NAM inhibited cell cycle progression, EMT (epithelial-mesenchymal transition), and invasion while it enhanced apoptosis of intrahepatic cholangiocarcinoma (bile duct carcinoma) in vitro [128].…”

Section: Breastmentioning

confidence: 99%

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The Role of Nicotinamide in Cancer Chemoprevention and Therapy

2020

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Nicotinamide (NAM) is a water-soluble form of Vitamin B3 (niacin) and a precursor of nicotinamide-adenine dinucleotide (NAD+) which regulates cellular energy metabolism. Except for its role in the production of adenosine triphosphate (ATP), NAD+ acts as a substrate for several enzymes including sirtuin 1 (SIRT1) and poly ADP-ribose polymerase 1 (PARP1). Notably, NAM is an inhibitor of both SIRT1 and PARP1. Accumulating evidence suggests that NAM plays a role in cancer prevention and therapy. Phase III clinical trials have confirmed its clinical efficacy for non-melanoma skin cancer chemoprevention or as an adjunct to radiotherapy against head and neck, laryngeal, and urinary bladder cancers. Evidence for other cancers has mostly been collected through preclinical research and, in its majority, is not yet evidence-based. NAM has potential as a safe, well-tolerated, and cost-effective agent to be used in cancer chemoprevention and therapy. However, more preclinical studies and clinical trials are needed to fully unravel its value.

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