Curcumol Induces Apoptosis in SPC-A-1 Human Lung Adenocarcinoma Cells and Displays Anti-neoplastic Effects in Tumor Bearing Mice

Tang, Qiyun; Guo, Jiquan; Wang, Qiyou; Lin, Hai‐Shu; Zou, Yang; Peng, Tong; Pan, Xuediao; Liu, Bing; Wang, Sujun; Zang, Lei

doi:10.7314/apjcp.2015.16.6.2307

Cited by 29 publications

(17 citation statements)

References 15 publications

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“…Data obtained from flow cytometry and cellular morphology studies demonstrate that curcumol is capable of inhibiting the growth of TNBC MDA-MB 231 cells in a predominantly apoptotic manner. These results are consistent with those observed in various other tumor cell lines (14)(15)(16)(17). Furthermore, the present study supported the evidence indicating a marked effect of curcumol in a BALB/c nude mice xenograft model.…”

Section: Discussionsupporting

confidence: 82%

“…China (11). Curcumol is one of the major pharmacological components of the aforementioned essential oil, and has recently been reported to exhibit an anti-proliferative effect on numerous human tumor cell lines, including lung, breast, ovary, liver, gastric and intestinal cancer (14)(15)(16)(17). To the best of our knowledge, the present study is the first to provide evidence of the anticancer effect of curcumol in a p53 mutant TNBC MDA-MB-231 cell line, via demonstrating a direct inhibition of cellular viability and xenograft growth, and the induction of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…A total of six volatile compounds (curdione, curcumol, germacrone, curzerene, 1,8-cineole and β-elemene) have been successfully isolated from the essential oil of Curcuma wenyujin (12). As one of the major components of the essential oil, curcumol, Curcumol triggers apoptosis of p53 mutant triple-negative human breast cancer MDA-MB 231 cells via activation of p73 and PUMA C 15 H 24 O 2-(3s-(3a, 3aa,5a,6a,8ab))-octahydro-3-methyl-8-methylene-5-(1-methylethyl)-6h-3a, 6-epoxyazulen-6-ol (13), has been reported to be capable of blocking the proliferation of various types of human tumor cells, including lung, prostate and ovarian cancer cell lines in vitro and inducing apoptosis via a caspase-independent mitochondrial pathway in ASTC-a-1 cells (14)(15)(16)(17). However, the molecular mechanisms underlying curcumol-induced anti-proliferative effects are still unknown.…”

Section: Curcuma Wenyujin Y H Chen Et C Ling (Curcuma Wenyujin)mentioning

confidence: 99%

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Curcumol triggers apoptosis of p53 mutant triple-negative human breast cancer MDA-MB 231 cells via activation of p73 and PUMA

Huang

Liao

et al. 2017

Oncology Letters

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Abstract. Triple-negative breast cancer (TNBC; estrogen receptor-negative, progesterone receptor-negative and Her-2-negative) is often accompanied by a higher frequency of p53 gene mutations. Therefore, TNBC is challenging to treat due to a lack of biological targets and a poor sensitivity to conventional therapies. Curcumol is a monomer composition isolated from the ethanol extracts of Curcuma wenyujin, a Chinese medicinal herb traditionally used as a cancer remedy. Previous studies have revealed that curcumol is able to block proliferation in various human tumor cell lines. However, the underlying mechanisms have yet to be elucidated. The present study aimed to investigate the anticancer effects of curcumol in the human p53 mutant TNBC MDA-MB-231 cell line and its underlying mechanisms. Cell viability and growth were determined by MTT and a mice xenograft model assay, respectively. Cell cycle distribution was examined by flow cytometry. Apoptosis was evaluated by apoptotic morphology analysis with DAPI staining and flow cytometric analysis following Annexin V/propidium iodide staining. The protein expression in cells was eva luated by immunoblotting. Treatment of MDA-MB-231 cells with curcumol resulted in a significant inhibition of cell proliferation in vitro [half maximal inhibitory concentration (IC 50 )=240.7±85.0 µg/ml for 48 h and IC 50 =100.2±13.5 µg/ml for 72 h]. Curcumol treatment also resulted in the suppression of xenograft growth in vivo (100 or 200 µg/kg for 21 days), as well as G 1 phase arrest and an apoptotic response, which were accompanied by the upregulation of p73 expression and the activation of the expression of p53 upregulated modulator of apoptosis (PUMA) and Bcl-2 antagonistic killer (Bak). No cleavage of poly (ADP-ribose) polymerase was detected. To the best of our knowledge, the present data demonstrate for the first time that curcumol inhibits the growth of MDA-MB-231 cells and triggers p53-independent apoptosis, which may be media ted by the p73-PUMA/Bak signaling pathway. Curcumol may, therefore, be a potential compound for use in the development of novel TNBC therapeutics. IntroductionTriple-negative breast cancer (TNBC; estrogen receptor-negative, progesterone receptor-negative and Her-2-negative) remains challenging to treat due to the innate aggressive biological characteristics and the lack of effective therapies (1,2). TNBCs represent ~15% of all breast cancer cases and are often accompanied by a higher frequency of p53 gene mutations (2,3). The tumor suppressor gene p53 serves a critical role in conferring cancer cell sensitivity to DNA-damaging agents (3). Failure of p53 signaling leads to resistance to chemotherapeutics (3-5). p73 is a member of the p53 gene family. Under certain conditions, p73 is able to replace the p53 function in response to DNA damage, activate the transcription of p53-responsive genes and inhibit cell growth in a p53-like manner by inducing cell cycle arrest and apoptosis (6-8). Therefore, the identification of anticancer drugs able to activate p73 ...

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Curcuma Wenyujin Y H Chen Et C Ling (Curcuma Wenyujin)mentioning

confidence: 99%

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Curcumol triggers apoptosis of p53 mutant triple-negative human breast cancer MDA-MB 231 cells via activation of p73 and PUMA

Huang

Liao

et al. 2017

Oncology Letters

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“…ASTC-a-1cells treated with curcumol displayed nuclear shrinkage, membrane blebbing, membrane frilling along with G2/M cell cycle arrest [52]. SPC-A-1, TE-1, and AGS cells displayed substantial G0/G1 arrest while TE-1, AGS, and MGC-803 exhibited G2/M arrest followed by the treatment of curcumol [23,32,65]. Curcumol significantly prohibited growth of CNE-2 cells and caused cell cycle arresting at G0/G1 phase via increasing the expression of p21 and p27 while reducing the expression of CDKs and cyclins in a dose-dependent mode [63].…”

Section: Curcumol and Cell Cycle Arrestmentioning

confidence: 99%

“…Dried roots of C. zedoary enriched with curcumol are documented for their effective anticancer and antiinflammatory properties [28][29][30][31]. Rhizome of various Curcuma species, a rich source of curcumol, serves as antimicrobial, antifibrotic, and anticancer agent [32][33][34]. Besides them, curcumol has also been isolated from the roots of Astragali radix, C. rhizoma, and Fructus gardenia which are traditionally used as anticancer agents [35,36].…”

Section: Curcumol and Its Natural Sourcesmentioning

confidence: 99%

Curcumol: From Plant Roots to Cancer Roots

et al. 2019

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Natural products, an infinite treasure of bioactive scaffolds, have provided an excellent reservoir for the discovery of drugs since millennium. These naturally occurring, biologically active and therapeutically effective chemical entities have emerged as novel paradigm for the prevention of various diseases. This review aims to give an update on the sources as well as pharmacological profile of curcumol, a pharmacologically active sesquiterpenoid, which is an imperative bioactive constituent of several plants mainly from genus Curcuma. Curcumol has potential to fight against cancer, oxidative stress, neurodegeneration, microbial infections, and inflammation. Curcumol has been documented as potent inducer of apoptosis in numerous cancer cells via targeting key signaling pathways as MAPK/ERK, PI3K/Akt and NF-κB which are generally deregulated in several cancers. The reported data reveals multitarget activity of curcumol in cancer treatment suggesting its importance as anticancer drug in future. It is speculated that curcumol may provide an excellent opportunity for the cure of cancer but further investigations on mechanism of its action and preclinical trials are still mandatory to further validate the potential of this natural cancer killer in anticancer therapies.

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Curcumol induces cell cycle arrest and apoptosis by inhibiting IGF‐1R/PI3K/Akt signaling pathway in human nasopharyngeal carcinoma CNE‐2 cells

Liu

Wang

et al. 2018

Phytotherapy Research

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Curcumol has been proved to possess antitumor effects in vivo and in vitro in several cancers. Previously, we have found that curcumol induced apoptosis in CNE-2 cells, but its underlying mechanism has not yet been studied well. Recently, our team clarified that curcumol inhibited colorectal cancer cells' growth partially through insulin-like growth factor 1 receptor (IGF-1R) pathway. Given the key importance of IGF-1R pathway in tumorigenesis, we want to explore whether curcumol effects on nasopharyngeal carcinoma (NPC) cells relates to IGF-1R and its downstream pathway inactivation. In this study, we found that curcumol inhibited IGF-1R and p-Akt expression in a dose- and time-dependent way. In addition, it also regulated their downstream GSK-3β's activity in CNE-2 cells, which further triggering alterations in the expression of cycle- and apoptosis-related molecules, and then leading to G0/G1-phase arrest and apoptosis. Moreover, curcumol's effect on CNE-2 cells was partly eliminated by IGF-1R's agonist IGF-1. In conclusion, our findings indicated that the inhibitory effect of curcumol on proliferation of NPC cells is related to the inhibition of IGF-1R and its downstream PI3K/Akt/GSK-3β pathway.

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Curcumol Induces Apoptosis in SPC-A-1 Human Lung Adenocarcinoma Cells and Displays Anti-neoplastic Effects in Tumor Bearing Mice

Cited by 29 publications

References 15 publications

Curcumol triggers apoptosis of p53 mutant triple-negative human breast cancer MDA-MB 231 cells via activation of p73 and PUMA

Curcumol triggers apoptosis of p53 mutant triple-negative human breast cancer MDA-MB 231 cells via activation of p73 and PUMA

Curcumol: From Plant Roots to Cancer Roots

Curcumol induces cell cycle arrest and apoptosis by inhibiting IGF‐1R/PI3K/Akt signaling pathway in human nasopharyngeal carcinoma CNE‐2 cells

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