Zerumbone inhibits interleukin-6 and induces apoptosis and cell cycle arrest in ovarian and cervical cancer cells

Abdelwahab, Siddig Ibrahim; Abdul, Ahmad Bustamam; Zain, Z.N.; Hadi, A. Hamid A.

doi:10.1016/j.intimp.2012.01.014

Cited by 80 publications

(51 citation statements)

References 38 publications

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“…Zerumbone has been documented to induce both intrinsic (mitochondria involved) and extrinsic (death receptor involved) apoptosis pathways that result in activation of caspase cascade (Prasannan et al 2012;Sobhan et al 2013;Xian et al 2007). Furthermore, induction of G2/M arrest of cell cycle has been reported to zerumbone action although there is no clear identification for G2 or mitotic phase arrest in the study (Abdelwahab et al 2012;Xian et al 2007; Kirana et al 2003). Zerumbone-signaled intracellular pathways have been characterized; however, the primary anticancer target and undiscovered signaling have not yet been investigated.…”

Section: Introductionmentioning

confidence: 87%

Zerumbone, a ginger sesquiterpene, induces apoptosis and autophagy in human hormone-refractory prostate cancers through tubulin binding and crosstalk between endoplasmic reticulum stress and mitochondrial insult

Chan

Liang

Hsu

et al. 2015

Naunyn-Schmiedeberg's Arch Pharmacol

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Zerumbone, a natural monocyclic sesquiterpene, is the main component of the tropical plant Zingiber zerumbet Smith. Zerumbone induced antiproliferative and apoptotic effects against PC-3 and DU-145, two human hormone-refractory prostate cancer (HRPC) cell lines. Zerumbone inhibited microtubule assembly and induced an increase of MPM-2 expression (specific recognition of mitotic proteins). It also caused an increase of phosphorylation of Bcl-2 and Bcl-xL, two key events in tubulin-binding effect, indicating tubulin-binding capability and mitotic arrest to zerumbone action. Furthermore, zerumbone induced several cellular effects distinct from tubulin-binding properties. First, zerumbone significantly increased, while paclitaxel (as a tubulin-binding control) decreased, Mcl-1 protein expression. Second, paclitaxel but not zerumbone induced Cdk1 activity. Third, zerumbone other than paclitaxel induced Cdc25C downregulation. The data suggest that, in addition to targeting tubulin/microtubule, zerumbone may act on other targets for signaling transduction. Zerumbone induced mitochondrial damage and endoplasmic reticulum (ER) stress as evidenced by the loss of mitochondrial membrane potential and upregulation of GRP-78 and CHOP/GADD153 expression. Zerumbone induced an increase of intracellular Ca(2+) levels, a crosstalk marker between ER stress and mitochondrial insult, associated with the formation of active calpain I fragment. It induced apoptosis through a caspase-dependent way and caused autophagy as evidenced by dramatic LC3-II formation. In summary, the data suggest that zerumbone is a multiple targeting compound that inhibits tubulin assembly and induces a crosstalk between ER stress and mitochondrial insult, leading to apoptosis and autophagy in HRPCs.

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Section: Introductionmentioning

confidence: 87%

Zerumbone, a ginger sesquiterpene, induces apoptosis and autophagy in human hormone-refractory prostate cancers through tubulin binding and crosstalk between endoplasmic reticulum stress and mitochondrial insult

Chan

Liang

Hsu

et al. 2015

Naunyn-Schmiedeberg's Arch Pharmacol

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“…These results suggested the mitochondrial pathway of cell apoptosis in [YbCit2] 3− -treated cells, which will help in understanding the molecular mechanisms of lanthanide-induced apoptosis in tumor cells. Furthermore, Abdelwahab et al [24] investigated the role of interleukin-6 (IL-6) and IL-6 receptors in the cytotoxic effects of zerumbone in ovarian and cervical cancer cell lines. Exposure of both cancer cells to zerumbone and cisplatin demonstrated the growth inhibition in a dose-dependent manner as determined by the MTT reduction assay.…”

Section: Herbal Drugs For the Treatment Of Cervical Cancermentioning

confidence: 99%

“…The results suggested a mitochondrial pathway of cell apoptosis in [YbCit2] 3− -treated cells, which expressed molecular mechanisms of lanthanide-induced apoptosis in tumor cells. In another study, Abdelwahab et al [96] investigated the role of IL-6 and IL-6 receptors in the cytotoxic effects of zerumbone in ovarian and cervical cancer cell lines (Caov-3 and HeLa, respectively) using MTT assay. The studies suggested that zerumbone-induced cell death by stimulating apoptosis was found to be better than cisplatin, with significantly higher percentage of apoptotic cells in zerumbone’s treated cancer cells as compared with cisplatin as analyzed by flow cytometry.…”

Section: Systemic Versus Localized Drug Delivery Systemsmentioning

confidence: 99%

Possible role of nanocarriers in drug delivery against cervical cancer

Gupta

2017

Nano Reviews & Experiments

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Introduction: Cervical cancer is the second most common cancer and the largest cancer killer among women in most developing countries including India. Although, various drugs have been developed for cervical cancer, treatment with these drugs often results in a number of undesirable side effects, toxicity and multidrug resistance (MDR). Also, the outcomes for cervical cancer patients remain poor after surgery and chemo radiation. Methods: A literature search (for drugs and delivery systems against cervical cancer) was performed on PubMed and through Google. The present review discuss about various methods including its current conventional treatment with special reference to recent advances in delivery systems encapsulating various anticancer drugs and natural plant products for targeting towards cervical cancer. The role of photothermal therapy, gene therapy and radiation therapy against cervical cancer is also discussed. Results: Systemic/targeted drug delivery systems including liposomes, nanoparticles, hydrogels, dendrimers etc. and localized drug delivery systems like cervical patches, films, rings etc. are safer than the conventional chemotherapy which has further been proved by the several drug delivery systems undergoing clinical trials. Conclusion: Novel approaches for the aggressive treatment of cervical cancer will optimistically result in decreased side effects as well as toxicity, frequency of administration of existing drugs, to overcome MDR and to increase the survival rates.

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“…Its structure possesses three double bonds, two conjugated and one isolated, as well as double conjugated carbonyl group in the 11-membrane ring structure [3] and has been found to possess many biomedical properties such as antiproliferative, antioxidant, antiinflammatory [4][5][6], anticancer [7][8][9][10], and antimicrobial [11][12][13] activities. It possesses antiproliferative properties toward several cancer cell lines mainly on human cervical cancer (HeLa) cell line [14].…”

Section: Introductionmentioning

confidence: 99%

Zerumbone, a Natural Plant Dietary Compound Induces Expression of Interleukin-12p70 Cytokine in Human Peripheral Blood Mononuclear Cells

Dash¹,

Ray²,

Mishra³

et al. 2016

Asian J Pharm Clin Res

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Objective: Despite possessing many biological activities as antiproliferative, antioxidant, anti-inflammatory, and anticancerous, and zerumbone lacks any evidence for its immunomodulatory activity. This naturally occurring dietary compound needs to be developed as drug to support therapeutic claims in various infections and diseases.Methods: Hence, in this study, the immunomodulatory effects of zerumbone were investigated by evaluating the effect of this compound toward the lymphocytes proliferation in human peripheral blood mononuclear cells. Results:Lymphocyte proliferation assay showed that zerumbone was able to activate human lymphocytes at dosage-dependent manner at the highest concentration 40 µl/mL. The production of human interleukin-12p70 cytokine in culture supernatant from activated lymphocytes was upregulated by zerumbone at 24 hrs and gradually decreased at 48 hrs. Hence, the study confirms the immunomodulatory activity of zerumbone which play an important role in boosting up the immune system through cytokine production in dosage dependent manner. Conclusion:The study concludes that zerumbone could be used as a lead molecule in herbal therapeutic world as an immunomodulatory drug in the treatment of chronic infections and various autoimmune disorders.

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Zerumbone inhibits interleukin-6 and induces apoptosis and cell cycle arrest in ovarian and cervical cancer cells

Cited by 80 publications

References 38 publications

Zerumbone, a ginger sesquiterpene, induces apoptosis and autophagy in human hormone-refractory prostate cancers through tubulin binding and crosstalk between endoplasmic reticulum stress and mitochondrial insult

Zerumbone, a ginger sesquiterpene, induces apoptosis and autophagy in human hormone-refractory prostate cancers through tubulin binding and crosstalk between endoplasmic reticulum stress and mitochondrial insult

Possible role of nanocarriers in drug delivery against cervical cancer

Zerumbone, a Natural Plant Dietary Compound Induces Expression of Interleukin-12p70 Cytokine in Human Peripheral Blood Mononuclear Cells

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