Induction of apoptosis and proliferation inhibition of hepatocellular carcinoma by 6-chloro-2-methoxy-N-(phenylmethyl)-9-acridinamine (BA): in vitro and vivo studies

Huang, Yun; Liu, Guohua; Yang, Feng; Xing, Xiaowei; Li, Ying; Huang, Zhijun; Yuan, Hong

doi:10.1186/s12935-017-0435-5

Cited by 5 publications

(7 citation statements)

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“…Various natural compounds such as resveratrol, curcumin have shown anti-cancer and anti-metastatic efficacy by suppression of PI3K/AKT signaling in HCC [ 41 – 43 ]. Recently, it has shown that the effect of natural compounds on HCC is not less than that of approved anti-cancer drugs [ 25 , 44 ]. Indeed, Yun et al have reported that acridine amine, extracted from sponges (species) effectively inhibited tumor growth compared with 5-FU by blockade of PI3K/AKT pathway in HCC [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it has shown that the effect of natural compounds on HCC is not less than that of approved anti-cancer drugs [ 25 , 44 ]. Indeed, Yun et al have reported that acridine amine, extracted from sponges (species) effectively inhibited tumor growth compared with 5-FU by blockade of PI3K/AKT pathway in HCC [ 44 ]. Similar to previous studies, we found that LAC117 inhibited the activated PI3K/AKT signaling pathway via the decreases of p-AKT, p-mTOR, and p-GSK3β in HCC.…”

Section: Discussionmentioning

confidence: 99%

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Artemisia Capillaris leaves inhibit cell proliferation and induce apoptosis in hepatocellular carcinoma

Kim

Jung

Zhang

et al. 2018

BMC Complement Altern Med

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BackgroundNatural product is one of the most important sources of drugs used in pharmaceutical therapeutics. Artemisia capillaris has been traditionally used as a hepatoprotective and anti-inflammatory agent. In this study, we extracted an ethanol fraction (LAC117) from the dried leaves of Artemisia capillaris and identified its anticancer activity and mechanism of action against hepatocellular carcinoma (HCC).MethodsAnti-proliferative effect of LAC117 was evaluated by MTT assay and BrdU assay. The apoptotic effect of LAC117 on the expression of cleaved PARP and cleaved caspase-3 was evaluated by Western blot and immunohistochemistry from in vivo mouse xenograft, respectively.ResultsWe found that LAC117 strongly suppressed the growth and proliferation of human HCC cell lines (HepG2 and Huh7). Induction of apoptosis was evidenced by the increases of cleaved caspase-3 and PARP as well as TUNEL-positive cells. Additionally, the pro-apoptotic effect of LAC117 was observed by a decrease in the expression of the XIAP and an increase in cytochrome c releases via mitochondrial membrane potential. Moreover, it significantly inhibited PI3K/AKT pathway in HCC in vivo and in vitro. LAC117 suppressed tumor growth in an ex vivo model as well as in vivo mouse xenograft by inducing apoptosis and inhibiting tumor cell proliferation.ConclusionsThe present study highlights that LAC117 could not only efficiently induce apoptosis, but also inhibit the growth of human HCC cells by blocking the PI3K/AKT signaling pathway, suggesting that LAC117 would be a potentially useful drug candidate against HCC.Electronic supplementary materialThe online version of this article (10.1186/s12906-018-2217-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Artemisia Capillaris leaves inhibit cell proliferation and induce apoptosis in hepatocellular carcinoma

Kim

Jung

Zhang

et al. 2018

BMC Complement Altern Med

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“…In vivo anticancer activity was assessed in mice administered i.p. with 5 or 10 mg/Kg of BA once a day for five consecutive days [72]. Notably, 10 mg/Kg of BA was more efficient than 10 mg/Kg of 5-fluorouracil at reducing tumor growth [72].…”

Section: Spongesmentioning

confidence: 99%

“…with 5 or 10 mg/Kg of BA once a day for five consecutive days [72]. Notably, 10 mg/Kg of BA was more efficient than 10 mg/Kg of 5-fluorouracil at reducing tumor growth [72]. Recently, our research group identified two marine sponge compounds isolated from Western Australian sponges: Crambescidin 800 and Aurantoside C from the species Monachora viridis and Manihinea lynbeazleyae, respectively [73,74].…”

Section: Spongesmentioning

confidence: 99%

From Seabed to Bedside: A Review on Promising Marine Anticancer Compounds

et al. 2020

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The marine environment represents an outstanding source of antitumoral compounds and, at the same time, remains highly unexplored. Organisms living in the sea synthesize a wide variety of chemicals used as defense mechanisms. Interestingly, a large number of these compounds exert excellent antitumoral properties and have been developed as promising anticancer drugs that have later been approved or are currently under validation in clinical trials. However, due to the high need for these compounds, new methodologies ensuring its sustainable supply are required. Also, optimization of marine bioactives is an important step for their success in the clinical setting. Such optimization involves chemical modifications to improve their half-life in circulation, potency and tumor selectivity. In this review, we outline the most promising marine bioactives that have been investigated in cancer models and/or tested in patients as anticancer agents. Moreover, we describe the current state of development of anticancer marine compounds and discuss their therapeutic limitations as well as different strategies used to overcome these limitations. The search for new marine antitumoral agents together with novel identification and chemical engineering approaches open the door for novel, more specific and efficient therapeutic agents for cancer treatment.

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“…Therefore, there is an increasing need to reassess the overwhelming emphasis on molecular targeting [1]. Many strong anticancer agents isolated from marine sponges have potential clinical value [[2], [3], [4], [5], [6], [7]]. The quantity of extractable sponge biomass available from the sea cannot meet the demand for large-scale research or clinical development of anticancer compounds.…”

Section: Introductionmentioning

confidence: 99%

Primmorph extracts and mesohyls of marine sponges inhibit proliferation and migration of hepatocellular carcinoma cells in vitro

Rady

Salem

El-Arab

2019

Journal of Pharmaceutical Analysis

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Cancer recurrence and severe side effects of currently being used chemotherapeutic agents reduce their clinical efficacy. Thus, there is a constant need to develop alternative anticancer drugs. Sustainable supply is an important challenge facing marine-based drug discovery. Primmorph, a 3D cell culture system, could provide a sustainable source to produce metabolites for anticancer drugs from marine sponges. In the present work, the anticancer activity of primmorph extracts and mesohyls of Negombata magnifica , Hemimycle arabica, Crella spinulata , and Stylissa carteri sponges was evaluated. Antiproliferative activity was studied in terms of cytotoxicity, colony formation, cell cycle, and apoptosis. Migration was assessed by migration assay and matrix metalloproteinase activity. The expression of proliferation and migration-related genes was analyzed using real time PCR. Migration and proliferation activities of HepG2 cells were inhibited by treatment with primmorph extracts and mesohyls of N. magnifica , H. arabica , and C. spinulata . The mesohyl of S. carteri did not show any anticancer activity although the primmorph extract led to cell cycle arrest. Among the selected sponge species, the primmorph extract of C. spinulata was the most promising anticancer agent regarding antiproliferative and antimigratory activities. In addition, primmorph extracts have the advantage of working under well-defined and controlled conditions, which allows the easy application as a bioreactor.

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Induction of apoptosis and proliferation inhibition of hepatocellular carcinoma by 6-chloro-2-methoxy-N-(phenylmethyl)-9-acridinamine (BA): in vitro and vivo studies

Cited by 5 publications

References 31 publications

Artemisia Capillaris leaves inhibit cell proliferation and induce apoptosis in hepatocellular carcinoma

Artemisia Capillaris leaves inhibit cell proliferation and induce apoptosis in hepatocellular carcinoma

From Seabed to Bedside: A Review on Promising Marine Anticancer Compounds

Primmorph extracts and mesohyls of marine sponges inhibit proliferation and migration of hepatocellular carcinoma cells in vitro

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