Aloperine induces G2/M phase cell cycle arrest and apoptosis in HCT116 human colon cancer cells

Zhang, Li; Zheng, Yao; Deng, Hong-zhu; Liu, Liang; Peng, Juan

doi:10.3892/ijmm.2014.1718

Cited by 77 publications

(67 citation statements)

References 31 publications

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“…However, pretreatment of mice with aloperine prevented tubular cells from IRinduced apoptosis as evidenced by the significant reduction of TUNELpositive tubular cells and decreased protein levels for caspase3. This finding somehow is in conflict with studies in tumor cells in which aloperine was noted to promote cancer or tumor cell apoptosis (26,66). To confirm this observation, we cultured HK2 cells under hypoxic conditions in the presence of aloperine and similar results were obtained (data not shown).…”

Section: Discussionmentioning

confidence: 67%

Aloperine Protects Mice against Ischemia-Reperfusion (IR)-Induced Renal Injury by Regulating PI3K/AKT/mTOR Signaling and AP-1 Activity

Zhang

et al. 2015

Mol Med

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Aloperine is a quinolizidine alkaloid extracted from the leaves of Sophora plants. It has been recognized with the potential to treat inflammatory and allergic diseases as well as tumors. In this report, we demonstrate that pretreatment with aloperine provided protection for mice against ischemia-reperfusion (IR)-induced acute renal injury as manifested by the attenuated inflammatory infiltration, reduced tubular apoptosis, and well-preserved renal function. Mechanistic studies revealed that aloperine selectively repressed IL-1β and IFN-γ expression by regulating PI3K/Akt/mTOR signaling and NF-κB transcriptional activity. However, aloperine did not show a perceptible impact on IL-6 and TGF-β expression and the related Jak2/Stat3 signaling. It was also noted that aloperine regulates AP-1 activity, through which it not only enhances SOD expression to increase reactive oxygen species (ROS) detoxification but also promotes the expression of antiapoptotic Bcl-2, thereby preventing tubular cells from IR-induced apoptosis. Collectively, our data suggest that administration of aloperine prior to IR insults, such as renal transplantation, could be a viable approach to prevent IR-induced injuries.

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Section: Discussionmentioning

confidence: 67%

Aloperine Protects Mice against Ischemia-Reperfusion (IR)-Induced Renal Injury by Regulating PI3K/AKT/mTOR Signaling and AP-1 Activity

Zhang

et al. 2015

Mol Med

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“…ALO has been reported to have a large range of biological effects, including anti-inflammatory, anti-allergenic, anti-tumor, and antiviral reactions [7]. Recently, we reported ALO to have antinociceptive effects on neuropathic pain induced by chronic constriction injury, in which antioxidants are involved as one of the mechanisms [8].…”

Section: Introductionmentioning

confidence: 98%

“…Aloperine (ALO) is a quinolizidine alkaloid, which has been isolated from the roots of Sophora alopecuroides L., a traditional Chinese medicine used for the treatment of cancer [7]. ALO has been reported to have a large range of biological effects, including anti-inflammatory, anti-allergenic, anti-tumor, and antiviral reactions [7].…”

Section: Introductionmentioning

confidence: 99%

Protective effects of aloperine on neonatal rat primary cultured hippocampal neurons injured by oxygen–glucose deprivation and reperfusion

Zhou

Chang

et al. 2015

J Nat Med

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Aloperine (ALO), one of the alkaloids isolated from Sophora alopecuroides L., is traditionally used for various diseases including neuronal disorders. This study investigated the protective effects of ALO on neonatal rat primary-cultured hippocampal neurons injured by oxygen-glucose deprivation and reperfusion (OGD/RP). Treatment with ALO (25, 50, and 100 mg/l) attenuated neuronal damage (p < 0.01), with evidence of increased cell viability (p < 0.01) and decreased cell morphologic impairment. Furthermore, ALO increased mitochondrial membrane potential (p < 0.01), but inhibited intracellular-free calcium [Ca(2+)] i (p < 0.01) elevation in a dose-dependent manner at OGD/RP. ALO also reduced the intracellular reactive oxygen species and malondialdehyde production and enhanced the antioxidant enzymatic activities of catalase, superoxide dismutase, glutathione peroxidase and the total antioxidant capacity. The results suggested that ALO has significant neuroprotective effects that can be attributed to anti-oxidative stress.

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“…Aloperine exhibits antiinflammatory, anti-allergic [17,18], and antiviral activity [19]; inhibits proliferation of HCT116 cancer cells; initiates apoptosis; and interrupts the cell cycle [20].…”

mentioning

confidence: 99%

New Aloperine–Isoflavone Conjugates

2016

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The reaction of aloperine with isoflavone glycidyl ethers was investigated. A series of alkaloid-isoflavonoid conjugates were synthesized via regioselective opening of the oxirane ring by aloperine.Keywords: aloperine, isoflavone, propanolamine, isoflavone glycidyl ether.E-Adrenoblockers play an important role in the treatment of cardiovascular diseases. Their anti-ischemic, antiarrhythmic, and antihypertensive properties have been used in clinical medicine for many years. Derivatives of phenylpropanolamine and phenoxypropanolamine are typical E-adrenoreceptor blockers [1, 2]. Chromone and flavone derivatives containing a propanolamine fragment are also known to be capable of blocking E-adrenoreceptors [3,4]. Furthermore, several 7-(3-amino-2-hydroxypropoxy) flavonoid derivatives exhibited antihypertensive [5][6][7], antihyperglycemic [8], and antiproliferative [9] activity. Isoflavones containing an aminopropanol fragment showed anti-osteoporosis activity, an estrogen effect [10], and anticancer activity [11].In continuation of research on the synthesis of alkaloid-flavonoid conjugates, it seemed interesting to study the possibility of using a hydroxypropane linker to conjugate 7-hydroxyisoflavones and aloperine, which was isolated as a minor constituent from seeds and leaves of Sophora alopecuroides L. [12][13][14][15][16].Modification of this alkaloid was interesting because of its valuable biological properties. Aloperine exhibits antiinflammatory, anti-allergic [17,18], and antiviral activity [19]; inhibits proliferation of HCT116 cancer cells; initiates apoptosis; and interrupts the cell cycle [20].The phenols for conjugation with aloperine were the natural isoflavones formononetin 1a [21], 2-methylformononetin 1b [22], cladrin 1c [23], afromorsin 1d [24], cladrastin 1e [23], pseudobaptigenin 1f [25], and their derivatives 1g-j.Oxiranes are widely used to synthesize phenoxypropanolamines. Their cyclic system can be opened highly regioselectively by N-nucleophiles. Thus, the most common method for synthesizing phenol glycidyl ethers uses attack of the phenols at the oxirane ring of 1-chloro-2,3-epoxypropane (epichlorohydrin) to give the chlorohydrin ethers followed by dehydrochlorination by base to close the epoxide ring [4,5,26,27].

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Aloperine induces G2/M phase cell cycle arrest and apoptosis in HCT116 human colon cancer cells

Cited by 77 publications

References 31 publications

Aloperine Protects Mice against Ischemia-Reperfusion (IR)-Induced Renal Injury by Regulating PI3K/AKT/mTOR Signaling and AP-1 Activity

Aloperine Protects Mice against Ischemia-Reperfusion (IR)-Induced Renal Injury by Regulating PI3K/AKT/mTOR Signaling and AP-1 Activity

Protective effects of aloperine on neonatal rat primary cultured hippocampal neurons injured by oxygen–glucose deprivation and reperfusion

New Aloperine–Isoflavone Conjugates

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