Phyllanthus amarus Inhibits Cell Growth and Induces Apoptosis in Dalton's Lymphoma Ascites Cells Through Activation of Caspase-3 and Downregulation of Bcl-2

Harikumar, Kuzhuvelil B.; Kuttan, Girija; Kuttan, Ramadasan

doi:10.1177/1534735408330713

Cited by 21 publications

(10 citation statements)

References 20 publications

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“…This finding is supported by other studies that showed that plants of the Euphorbiaceae family present the ability to cause accentuated cell death in tumour cell lines after treatment with their extracts (Giridharan et al, 2002;Harikumar et al, 2009).…”

Section: Discussionsupporting

confidence: 87%

Antitumoural effect of Synadenium grantii Hook f. (Euphorbiaceae) latex

Oliveira¹,

Munhoz²,

Lemes³

et al. 2013

Journal of Ethnopharmacology

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Section: Discussionsupporting

confidence: 87%

Antitumoural effect of Synadenium grantii Hook f. (Euphorbiaceae) latex

Oliveira¹,

Munhoz²,

Lemes³

et al. 2013

Journal of Ethnopharmacology

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“…Based on our data, apoptosis occurred in the cells treated with Phyllanthus as the level of these execution caspases was increased manifold over the basal level of untreated cells. This could be due to the presence of tannins (such as gallic acid and geraniin) in the Phyllanthus extracts which had been shown to be able to induce apoptosis in several human cancer cells [4], [44]. Activation of caspase-3 will subsequently trigger the proteolytic cleavage of poly ADP-ribose polymerase resulting in DNA fragmentation that usually occurs during late apoptosis [5], [45].…”

Section: Discussionmentioning

confidence: 99%

“…Phyllanthus can now be found in almost every tropical countries due to its wide medicinal usages and lack of toxicity [10], [11]. Various therapeutic properties of this genus have been reported, including being antihepatotoxic, antilithic, antihypertensive, and most recently anti-HIV as well [4], [10]–[14]. There are also some speculation on the anticarcinogenic activity of various Phyllanthus plants.…”

Section: Introductionmentioning

confidence: 99%

Antimetastatic Effects of Phyllanthus on Human Lung (A549) and Breast (MCF-7) Cancer Cell Lines

et al. 2011

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BackgroundCurrent chemotherapeutic drugs kill cancer cells mainly by inducing apoptosis. However, they become ineffective once cancer cell has the ability to metastasize, hence the poor prognosis and high mortality rate. Therefore, the purpose of this study was to evaluate the antimetastatic potential of Phyllanthus (P. niruri, P. urinaria, P. watsonii, and P. amarus) on lung and breast carcinoma cells.Methodology/Principal FindingsCytotoxicity of Phyllanthus plant extracts were first screened using the MTS reduction assay. They were shown to inhibit MCF-7 (breast carcinoma) and A549 (lung carcinoma) cells growth with IC50 values ranging from 50–180 µg/ml and 65–470 µg/ml for methanolic and aqueous extracts respectively. In comparison, they have lower toxicity on normal cells with the cell viability percentage remaining above 50% when treated up to 1000 µg/ml for both extracts. After determining the non-toxic effective dose, several antimetastasis assays were carried out and Phyllanthus extracts were shown to effectively reduce invasion, migration, and adhesion of both MCF-7 and A549 cells in a dose-dependent manner, at concentrations ranging from 20–200 µg/ml for methanolic extracts and 50–500 µg/ml for aqueous extracts. This was followed by an evaluation of the possible modes of cell death that occurred along with the antimetastatic activity. Phyllanthus was shown to be capable of inducing apoptosis in conjunction with its antimetastastic action, with more than three fold increase of caspases-3 and -7, the presence of DNA-fragmentation and TUNEL-positive cells. The ability of Phyllanthus to exert antimetastatic activities is mostly associated to the presence of polyphenol compounds in its extracts.Conclusions/SignificanceThe presence of polyphenol compounds in the Phyllanthus plant is critically important in the inhibition of the invasion, migration, and adhesion of cancer cells, along with the involvement of apoptosis induction. Hence, Phyllanthus could be a valuable candidate in the treatment of metastatic cancers.

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“…Our preliminary results indicated modulation in Bax/Bcl-2 protein expression after Synadenium umbellatum treatment (data not shown). Phyllantus amarus (Euphorbiaceae) induced apoptosis in Dalton's lymphoma ascitic cells by Bcl-2 downregulation and activation of caspase 3 (Harikumar et al, 2009). Furthermore, Phyllanthus urinaria L. induced apoptosis by Bcl-2 suppression and activation of caspases (Giridharan et al, 2002).…”

Section: Discussionmentioning

confidence: 98%

Investigation of Ehrlich ascites tumor cell death mechanisms induced by Synadenium umbellatum Pax.

Mota

Benfica

Batista

et al. 2012

Journal of Ethnopharmacology

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Our results demonstrated that S. umbellatum decreased the viability of EAT cells using both methods. Morphological analyses revealed that S. umbellatum-treatment induced EAT cell death by apoptotic pathway. We demonstrated the occurrence of reactive oxygen species (ROS) overgeneration, increased intracellular Ca(2+) concentration, alteration in mitochondrial membrane potential, phosphatydylserine externalization, and activation of caspases 3, 8, and 9. However, S. umbellatum produced myelotoxicity in bone marrow cells in a concentration-dependent manner. In comparison to EAT cells, the effects of S. umbellatum in bone marrow cells were 8-fold lower. Taken together, our results showed that S. umbellatum induced apoptosis in EAT cells at several levels and seems more toxic to tumor cells than to normal bone marrow cells.

show abstract

Phyllanthus amarus Inhibits Cell Growth and Induces Apoptosis in Dalton's Lymphoma Ascites Cells Through Activation of Caspase-3 and Downregulation of Bcl-2

Cited by 21 publications

References 20 publications

Antitumoural effect of Synadenium grantii Hook f. (Euphorbiaceae) latex

Antitumoural effect of Synadenium grantii Hook f. (Euphorbiaceae) latex

Antimetastatic Effects of Phyllanthus on Human Lung (A549) and Breast (MCF-7) Cancer Cell Lines

Investigation of Ehrlich ascites tumor cell death mechanisms induced by Synadenium umbellatum Pax.

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