Apoptotic effects of mahanine on human leukemic cells are mediated through crosstalk between Apo-1/Fas signaling and the Bid protein and via mitochondrial pathways

Bhattacharya, Sayantani Sarkar; Samanta, Suman Kumar; Tripathi, Rakshamani; Mallick, Asish; Chandra, Sarmila; Pal, Buddhadev; Shaha, Chandrima; Mandal, Chitra

doi:10.1016/j.bcp.2009.09.007

Cited by 79 publications

(63 citation statements)

References 45 publications

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“…The alkaloids mahanine (16), mahanimbicine (17) and mahanimbine (18) were isolated from M. koenigii, and showed a significant anti-tumor activity against MCF-7, HeLa and P388 cell lines 85 . Mahanine induces the death receptormediated extrinsic pathway of apoptosis in MOLT-3 cancer cells, while also inducing the mitochondria dependent intrinsic pathway of apoptosis in HL-60 86,87 . Furthermore, 34 essential oils have been isolated from the leaves of M. koenigii, and all of which showed potent anti-bacteria and cytotoxic effects in a dose dependent trend 85 .…”

Section: 20mentioning

confidence: 99%

Anti-cancer potential of South Asian plants

Rahman

2013

Nat. Prod. Bioprospect.

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Phyto-chemicals are increasingly being used in the treatment of cancer because of their availability, potential anti-cancer activity with less adverse effects when compared with chemotherapy. The variation of climate and geography in South Asian countries provides a nursing environment for the growth of versatile plant species, that are repeatedly drawing attention of the scientific community. In this review, we have focused on the anti-cancer potential of thirty plants, which are commonly found in Bangladesh, India, Nepal, Pakistan and Sri Lanka, with their mechanisms of action. In particular, we have discussed the bio-active components that display anti-cancer activity, which have been identified in these plants. This review may help researchers to profile plants with known anti-cancer effect of this region and further investigations of anti-cancer agents in medicinal plants from South Asia.

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Section: 20mentioning

confidence: 99%

Anti-cancer potential of South Asian plants

Rahman

2013

Nat. Prod. Bioprospect.

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“…Herbal anticancer agents are promising as they display reduced cytotoxicity (Newman et al 2000, Mann 2002). While studying herbal compounds, we have demonstrated previously that mahanine, a purified carbazole alkaloid derived from the edible plant Murraya koenigii, was a potential activator of the cellular death cascade in a leukemic model (Bhattacharya et al 2010). In another recent study, we have established that mahanine-induced reactive oxygen speciesmediated functional inhibition of Hsp90 chaperone activity, resulting in Hsp90-Cdc37 disruption, leads to apoptosis in pancreatic adenocarcinoma (Sarkar et al 2013).…”

Section: Introductionmentioning

confidence: 97%

Coupling G2/M arrest to the Wnt/β-catenin pathway restrains pancreatic adenocarcinoma

Sarkar¹,

Mandal²,

Sangwan³

et al. 2014

Endocrine-Related Cancer

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Abstractb-catenin plays a pivotal role in organogenesis and oncogenesis. Alterations in b-catenin expression are common in pancreatic cancer, which is an extremely aggressive malignancy with a notably poor prognosis. In this report, we analyzed the apoptotic activity of withanolide-D (witha-D), a steroidal lactone that was purified from an Indian medicinal plant, Withania somnifera, and its underlying mechanism of action. Witha-D induced apoptosis in pancreatic ductal adenocarcinoma cells by prompting cell-cycle arrest at the G2/M phase. This lactone abrogated b-catenin signaling in these cells regardless of disease grade, mutational status, and gemcitabine sensitivity. Witha-D also upregulated E-cadherin in most cells, thereby supporting the inversion of the epithelial-mesenchymal transition. Furthermore, the Akt/Gsk3b kinase cascade was identified as a critical mediator of G2/M regulation and b-catenin signaling. Witha-D deactivated Akt, which failed to promote Gsk3b deactivation phosphorylation. Consequently, activated Gsk3b facilitated b-catenin destruction in pancreatic carcinoma cells. The knockdown of Chk1 and Chk2 further activated Akt and reversed the molecular signal. Taken together, the results of the current study represent the first evidence of b-catenin signal crosstalk during the G2/M phase by functionally inactivating Akt via witha-D treatment in pancreatic cancer cells. In conclusion, this finding suggests the potential identification of a new lead molecule in the treatment of pancreatic adenocarcinoma.

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“…Bid, a Bcl-2 family protein, is the substrate of activated caspase 8, whose activation is regulated by the death receptor, mainly through Fas/FasL interaction [29]. In the present case, there was no significant change in pro-caspase 8 and Bid expression; this is because caspase 8 activation is regulated mainly through the Fas/FasL interaction but K562 cells are Fas/FasL deficient [30]. The absence of caspase 8 activation prevents cleavage of bid in this type of cells.…”

Section: Discussionmentioning

confidence: 42%

Corchorusin-D Directed Apoptosis of K562 Cells Occurs through Activation of Mitochondrial and Death Receptor Pathways and Suppression of AKT/PKB Pathway

Mallick

Pal

Vedasiromoni

et al. 2012

Cell Physiol Biochem

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Saponins, plant glycosides, have been reported to possess anti-cancer properties. Therefore the effect of corchorusin-D (COR-D), a compound isolated from Corchorus acutangulus, was studied in the chronic myelogenous leukemic cell line K562, using MTT assay, phase contrast and confocal microscopy, annexin V binding, cell cycle analysis and western blotting. COR-D inhibited cell growth in K562 cells and showed increased number of Annexin V FITC binding cells. Characteristic apoptotic changes, seen under phase contrast and confocal microscopes with accumulation of cells in the sub-G0 phase. The apoptosis involved drop in Bcl-2/Bax ratio, loss of mitochondrial membrane potential, release of cytochrome c in cytosol followed by activation of caspases 9 and 3, and cleavage of PARP. Down-regulation of pro-caspase 10 was observed along with formation of death-inducing signaling complex between TNF-R1 and TRADD. COR-D suppressed PDK1 and AKT with activation of MAP kinase family members ERK1/2, JNK1/2 and p38. Thus it induced apoptosis by activating mitochondrial and death receptor pathways and suppressing AKT/PKB rather than MAP kinase pathway. Significant enhancement of apoptosis, noted using specific inhibitors of ERK1/2, p38 and JNK1/2, suggests that COR-D can enhance apoptosis in K562 cells in combination with MAP kinase inhibitors.

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Apoptotic effects of mahanine on human leukemic cells are mediated through crosstalk between Apo-1/Fas signaling and the Bid protein and via mitochondrial pathways

Cited by 79 publications

References 45 publications

Anti-cancer potential of South Asian plants

Anti-cancer potential of South Asian plants

Coupling G2/M arrest to the Wnt/β-catenin pathway restrains pancreatic adenocarcinoma

Corchorusin-D Directed Apoptosis of K562 Cells Occurs through Activation of Mitochondrial and Death Receptor Pathways and Suppression of AKT/PKB Pathway

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