Identification of a Novel Calotropis procera Protein That Can Suppress Tumor Growth in Breast Cancer through the Suppression of NF-κB Pathway

Samy, Ramar Perumal; Rajendran, Peramaiyan; Li, Feng; Anandi, Narayana Moorthy; Stiles, Bradley G.; Ignacimuthu, Savarimuthu; Sethi, Gautam; Chow, Vincent T. K.

doi:10.1371/journal.pone.0048514

Cited by 34 publications

(12 citation statements)

References 62 publications

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“…[124] However, a novel protein that can suppress tumor growth in breast cancer through the suppression of NF-κB pathway has been identified in C. procera. [125] It also shows protective efficacy against acute and chronic liver injury generated by carbon tetrachloride [126] and display cytotoxic effects against KB cell lines [54] and human epidermal carcinoma of the nasophyrnx tissue. [127] Similarly, root bark of C. gigantea show anti-tumor activity against Ehrlich ascites carcinoma in Swiss albino mice, [118] while aqueous extract of the latex has been shown to inhibit cellular infiltration and afford protection against development of neoplastic changes in the transgenic mouse model of hepatocellular carcinoma.…”

Section: Wound Healing and Hepatoprotectivementioning

confidence: 99%

Ethnomedicinal, pharmaceutical and pesticidal uses ofCalotropis procera(Aiton) (Family: Asclepiadaceae)

Upadhyay¹

2014

Int J Green Pharm

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Caloropis procera is a multipurpose plant that is extensively used by traditional folk healers and local people for preparation of different drugs and ailments of choice to treat different diseases and disorders. Plant contains diverse phyto-chemicals which show various pharmaceutical and ethno-medicinal properties. Two related species are of Asclepiadaceae, Caloropis procera and Calotropis gigantea, and both possess enormous disease curing potential against various infectious agents such as bacteria, viruses, fungi, protozoans and worms; and are widely used for treatment of different diseases and physiological disorders. Active components of Calotropis procera displayed cytostatic, cytotoxic, wound healing, procogulant, analgesic, anticonvulsant, anti-arthritic, antidiabetic, hepatoprotective, anti-fertility, antipyretic, anti-coccidial, anticancer, antitumor and anti-inflammatory properties. Natural Calotropis latex in preserved and concentrated forms finds many pharmaceutical applications and may be more useful in interventional therapies, complementary and alternative medicine to cure different types of cancers. Latex can be used for preparation of various herbal drugs and drug templates which might be non-steroidal and show wider cancer suppressing efficacy in patients. Plant can become a future source of therapeutic drugs, pesticides and industrial products. It can be used for phyto-extraction of toxic chemicals and reclamation of polluted derelict lands.

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Section: Wound Healing and Hepatoprotectivementioning

confidence: 99%

Ethnomedicinal, pharmaceutical and pesticidal uses ofCalotropis procera(Aiton) (Family: Asclepiadaceae)

Upadhyay¹

2014

Int J Green Pharm

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“…Excessive or high levels of ROS indicate vigorous oxidative stress in cells, which may cause direct or indirect damage to the mitochondria and induce apoptosis. NF-kB is the nucleus transcription factor, the activation of which is closely linked to various disease processes including tumorigenesis, inflammation, proliferation, invasion, angiogenesis, and metastasis [18]. The subsequent increase of proapoptosis proteins also generated mitochondrial outer-membrane permeabilization and the release of cytochrome C, which then combined with apoptotic protease activating factor-1 and caspase-9 to form apoptotic bodies, activating the intracellular apoptosis pathway [17].…”

Section: Introductionmentioning

confidence: 99%

Inhibitory impacts of chemically modified tetracycline-3 and underlying mechanism in human cervical cancer cells

Zhao

Xu²,

Yang³

et al. 2013

Anti-Cancer Drugs

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Chemically modified tetracyclines (CMTs) have been rationally designed from tetracyclines. The CMTs that show the antimicrobial properties are eliminated, whereas matrix metalloproteinase inhibitory properties are retained. Interestingly, CMT-3 (COL-3, by eliminating the dimethylamino, methyl, and hydroxyl functionalities on the basic tetracycline structure), one of the CMTs, has shown strong anticancer activity. In this study, we found that CMT-3 showed dose-dependent and time-dependent cytotoxicity in HeLa and Siha cells, two human cervical cancer cell lines. HeLa cells were more sensitive to CMT-3 compared with Siha cells. The antiproliferation potential of CMT-3 was associated with the mitochondrial apoptosis pathway, increasing reactive oxygen species level, and proapoptosis protein (e.g. caspase-3) expression, but decreasing antiapoptosis protein expression (e.g. Bcl-2). N-acetylcysteine (a reactive oxygen species inhibitor) and Z-LEHD-FMK significantly reduced or blocked the apoptosis event resulting from cytotoxic effect of CMT-3. CMT-3 also induced G0/G1 phase arrest with the reduction of cell cycle regulatory protein cyclin E and the translocation of NF-κB from the cytoplasm to the nucleus. Our findings provide the important foundation for further investigation of the underlying mechanism for the anticancer activity of CMT-3 and the potential application of CMT-3 as a new therapeutic candidate for clinical cervical cancer therapy.

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“…NF-κB, a vital signalling pathway, regulates the expression of a large number of genes and its over-expression is implicated in many diseases (Hu et al, 2012;Samy et al, 2012). In unstimulated cells, The NF-κB p50/NF-κB p65 dimer is bound to IκBα.…”

Section: Figurementioning

confidence: 99%

Andrographolide derivative AL‐1 improves insulin resistance through down‐regulation of NF‐κB signalling pathway

Yan

Zhang

et al. 2015

British J Pharmacology

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BACKGROUND AND PURPOSEAndrographolide is the most active constituent of the medicinal plant Andrographis paniculata. Previously, we synthesized a novel andrographolide derivative AL-1, conjugating andrographolide with lipoic acid. Although the antioxidative and/or anti-inflammatory activity of AL-1 contributes to its cytoprotective effects, whether AL-1 can improve insulin resistance and the mechanisms responsible for its action have not been elucidated. EXPERIMENTAL APPROACHWe investigated the anti-hyperlipidaemic and anti-hyperglycaemic effects of AL-1 in a high-fat diet/streptozocin-induced animal diabetic model. In addition, we investigated the effect of AL-1 on the NF-κB signalling pathway in rat islet derived insulinoma cells (RIN-m cells) with a focus on the link between reactive oxygen species-associated inflammation and insulin resistance. KEY RESULTSAL-1, at doses of 40 and 80 mg·kg −1 , had a significant hypoglycaemic effect; it significantly reduced the level of cholesterol and increased HDL. AL-1 also reduced the homeostasis model assessment of insulin resistance and enhanced insulin sensitivity. In addition, AL-1 improved the morphology of pancreatic islets and their function. Furthermore, AL-1 suppressed high glucose-induced phosphorylation of p65 and IκBα in RIN-m cells. CONCLUSION AND IMPLICATIONSAL-1 has a hypoglycaemic effect and improves insulin resistance in type 2 diabetic rats. It protected islet from high glucose-induced oxidative damage by down-regulating the NF-κB signalling pathway. Further investigations of AL-1 as a promising new agent for treatment and/or prevention of diabetes are warranted. AbbreviationsHOMA-IR, homeostasis model assessment of insulin resistance; ISI, insulin sensitivity index; STZ, streptozocin BJP British Journal of Pharmacology

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Identification of a Novel Calotropis procera Protein That Can Suppress Tumor Growth in Breast Cancer through the Suppression of NF-κB Pathway

Cited by 34 publications

References 62 publications

Ethnomedicinal, pharmaceutical and pesticidal uses ofCalotropis procera(Aiton) (Family: Asclepiadaceae)

Ethnomedicinal, pharmaceutical and pesticidal uses ofCalotropis procera(Aiton) (Family: Asclepiadaceae)

Inhibitory impacts of chemically modified tetracycline-3 and underlying mechanism in human cervical cancer cells

Andrographolide derivative AL‐1 improves insulin resistance through down‐regulation of NF‐κB signalling pathway

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