Cytotoxic activity of amooranin and its derivatives

Rabi, Thangaiyan; Karunagaran, Devarajan; Mk, Nair; Bhattathiri, V.N.

doi:10.1002/ptr.803

Cited by 21 publications

(33 citation statements)

References 2 publications

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“…In this study, we demonstrated that AMR was much more potent in MDA-468 cells than MCF-7 cells. It should be pointed out that AMR inhibited cell growth or decrease cell survival not only in breast cells, but also in other types of cancer including human leukemia, uterine cervix, neuroblastoma, and colon cancer cells [5][6][7]. Many anti-cancer drugs can arrest cell cycle and then induce apoptosis [24,25].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, it is active against N-nitrosomethyl urea-induced mammary adenocarcinoma in Sprague-Dawley rats [3]. AMR has been shown not only to be cytostatic but also cytotoxic to both hematopoitic and epithelial cell lines of diverse origin, including those derived from lung, uterine cervix carcinomas and multidrug-resistant subclones [5][6][7]. It is a potent inhibitor of photolabeling of P-glycoprotein (p-gp) with [ 3 H]-azidopine, including 104-fold doxorubicin-resistant CEM/VLB and 111-fold doxorubicin-resistant SW-620/Ad-300 cell lines, because it has been shown to competitively inhibit p-gp-mediated DOX efflux with increasing concentrations of AMR [6].…”

Section: Introductionmentioning

confidence: 99%

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Novel triterpenoid 25-hydroxy-3-oxoolean-12-en-28-oic acid induces growth arrest and apoptosis in breast cancer cells

Rabi

Wang

Banerjee

2006

Breast Cancer Res Treat

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25-Hydroxy-3-oxoolean-12-en-28-oic acid (Amooranin-AMR) is a triterpene acid isolated from the stem bark of a tropical tree (Amoora rohituka) grown wild in India. A herbal preparation used for the treatment of cancer by the Ayurvedic system of medicine contains the stem bark of Amoora rohituka as one of the ingredients. In this paper, we show that AMR displays a strong inhibitory effect on survival of human breast carcinoma MDA-468, breast adenocarcinoma MCF-7 cells compared to breast epithelial MCF-10A control cells. A 50% decrease in cells (IC50) ranged from 1.8 to 14.6 microM and cell growth was suppressed by arresting cell cycle at G2 + M phase. AMR effectively induces apoptosis and triggered a series of effects associated with apoptosis including cleavage of caspase-8, -9, -3, Bid and ER stress in MDA-468 cells and caspase- 8, -9, -6 and Bid in MCF-7 cells, release of cytochrome c from the mitochondria, cleavage of poly (ADP-ribose) polymerase (PARP) and DNA fragmentation with a concomitant upregulation of p53, Bax and down-regulation of Bcl-2 in MDA-468 cells, but Bax unchanged in MCF-7 cells. The use of caspase blocking peptides and acridine orange staining confirmed the involvement of primarily caspase-9 and -3 in MDA-468 cells with mutated p53 and primarily caspase-8, -9 and -6 in MCF-7 cells expressing wt p53. We also observed in MCF-7/p53siRNA cells AMR treatment caused reduced expression of Bcl-2 without affecting levels of Bax similar to MCF-7 cells treated with AMR and proteolytic activation of Bax in MDA-468 cells. These results suggest that AMR induces apoptosis in human breast carcinoma cells via caspase activation pathway and likely it is a p53-independent apoptosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel triterpenoid 25-hydroxy-3-oxoolean-12-en-28-oic acid induces growth arrest and apoptosis in breast cancer cells

Rabi

Wang

Banerjee

2006

Breast Cancer Res Treat

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“…One of these analogues, AMR-Me (Fig. 1B), was found to inhibit proliferation of several breast cancer cells with greater potency than the parent compound AMR [112]. Preliminary screening of AMR-Me in in vitro experiments revealed an astonishing potency against breast cancer MCF-7 cells with concentrations down to the nanomolar range.…”

Section: Triterpenoidsmentioning

confidence: 97%

“…1A), commonly known as amooranin (AMR), is a triterpene acid with a novel structure isolated by Rabi [111] from the stem bark of Amoora rohituka, a tropical tree growing wild in India. Recent studies by Rabi and colleagues [112][113][114] showed that multiple breast cancer cell lines respond to AMR in growth suppression assays. Mechanistic studies suggest that AMR suppresses growth factor signaling, induces cell cycle arrest, and promotes apoptosis [113,114].…”

Section: Triterpenoidsmentioning

confidence: 98%

Terpenoids and breast cancer chemoprevention

Rabi

Bishayee

2008

Breast Cancer Res Treat

208

107

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Cancer chemoprevention is defined as the use of natural or synthetic agents that reverse, suppress or arrest carcinogenic and/or malignant phenotype progression towards invasive cancer. Phytochemicals obtained from vegetables, fruits, spices, herbs and medicinal plants, such as terpenoids, carotenoids, flavanoids, phenolic compounds, and other groups of compounds have shown promise in suppressing experimental carcinogenesis in various organs. Recent studies have indicated that mechanisms underlying chemopreventive action may include combinations of anti-oxidant, anti-inflammatory, immune-enhancing, and anti-hormone effects. Further, modification of drug-metabolizing enzymes, and influences on cell cycling and differentiation, induction of apoptosis, and suppression of proliferation and angiogenesis that play a role in the initiation and secondary modification of neoplastic development, have also been under investigation as possible mechanisms. This review will highlight the biological effects of terpenoids as chemopreventive agents on breast epithelial carcinogenesis, and the utility of intermediate biomarkers as indicators of premalignancy. Selected breast chemoprevention trials are discussed with a focus on strategies for trial design, and clinical outcomes. Future directions in the field of chemoprevention are proposed based on recently acquired mechanistic insights into breast carcinogenesis.

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“…For HTB126, Panc-1, Mia-Paca2, and Capan-1 cancer cells, the CH 2 Cl 2 extract of dried whole plant showed a significant cytotoxic effect. [22][23][24][25][26][27][28] …”

Section: Antiaris Africanamentioning

confidence: 99%