4′-Demethyl-deoxypodophyllotoxin glucoside isolated from Podophyllum hexandrum exhibits potential anticancer activities by altering Chk-2 signaling pathway in MCF-7 breast cancer cells

Zilla, Mahesh K.; Nayak, Debasis; Amin, Hina; Nalli, Yedukondalu; Rah, Bilal; Chakraborty, Souneek; Kitchlu, Surender; Goswami, Anindya; Ali, Asif

doi:10.1016/j.cbi.2014.09.022

Cited by 43 publications

(34 citation statements)

References 36 publications

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“…It also prevents the growth of hepatocellular carcinoma cells through upregulation of A-kinase anchoring protein 12 (AKAP12) and transforming growth factor beta-2 (TGF-β2) proteins (Kuo et al, 2015). Podophyllotoxin blocks the growth of MCF-7 breast cancer cells by altering checkpoint kinase 2 (Chk-2) signaling pathway (Zilla et al, 2014). Podophyllotoxin also promotes apoptosis in non-small cell lung carcinoma cells through ER stress, autophagy and cell cycle arrest (Choi et al, 2015).…”

Section: Molecular Targets and Mechanisms Of Action Of Anticancer Phymentioning

confidence: 99%

Lead Phytochemicals for Anticancer Drug Development

et al. 2016

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Cancer is a serious concern at present. A large number of patients die each year due to cancer illnesses in spite of several interventions available. Development of an effective and side effects lacking anticancer therapy is the trending research direction in healthcare pharmacy. Chemical entities present in plants proved to be very potential in this regard. Bioactive phytochemicals are preferential as they pretend differentially on cancer cells only, without altering normal cells. Carcinogenesis is a complex process and includes multiple signaling events. Phytochemicals are pleiotropic in their function and target these events in multiple manners; hence they are most suitable candidate for anticancer drug development. Efforts are in progress to develop lead candidates from phytochemicals those can block or retard the growth of cancer without any side effect. Several phytochemicals manifest anticancer function in vitro and in vivo. This article deals with these lead phytomolecules with their action mechanisms on nuclear and cellular factors involved in carcinogenesis. Additionally, druggability parameters and clinical development of anticancer phytomolecules have also been discussed.

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Section: Molecular Targets and Mechanisms Of Action Of Anticancer Phymentioning

confidence: 99%

Lead Phytochemicals for Anticancer Drug Development

et al. 2016

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“…Mostly, anticancer compound induces apoptosis by targeting the specific events of cell cycle. Subsequent synthesis of S phase, cells enter into the growth (G2) phase, where repair mechanism takes place along with preparation for mitosis (M) phase and defects identified in the G2/Mcheck point may allow the damaged cell to undergo apoptosis [23]. Although the PCN-treated cancer cells did not exhibit cell cycle arrest, the sub-G phase was observed (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…ROS generation enhances mtDNA damage with decrease respiratory function due to disturbed electron transport chain that ultimately induces apoptosis [35]. In fact, most of the chemotherapeutic agents such as cisplatin, doxorubicin, paclitaxel and natural compounds like curcumin, epigallocatechin gallate (EGCG) and quercetin exhibit selective toxicity towards cancer cells by augmenting ROS stress [23,36,37].…”

Section: Discussionmentioning

confidence: 99%

“…Relative changes in intracellular ROS in A549 and MDA MB-231 cells were measured by detecting the conversion of cell permeable fluorescent probe 2,7-dichlorofluorescein diacetate (DCF-DA) to fluorescent dicholorfluorescein (DCF) [23]. Briefly, cells were seeded at a density of 3 9 10 6 cells ml -1 in 6-well plate and treated with IC 50 concentration of phenazine derivative for 48 h. After incubation, the cells were trypsinized and stained with 10 lM of DCF-DA followed by incubation for 45 min in dark.…”

Section: Determination Of Reactive Oxygen Species (Ros)mentioning

confidence: 99%

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Phenazine-1-carboxamide (PCN) from Pseudomonas sp. strain PUP6 selectively induced apoptosis in lung (A549) and breast (MDA MB-231) cancer cells by inhibition of antiapoptotic Bcl-2 family proteins

et al. 2015

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Phenazine-1-carboxamide (PCN), a naturally occurring simple phenazine derivative isolated from Pseudomonas sp. strain PUP6, exhibited selective cytotoxic activity against lung (A549) and breast (MDA-MB-231) cancer cell lines in differential and dose-dependent manner compared to normal peripheral blood mononuclear cells. PCN-treated cancer cells showed the induction of apoptosis as evidenced by the release of low level of LDH, morphological characteristics, production of reactive oxygen species, loss of mitochondrial membrane potential (ΔΨm) and induction of caspase-3. At molecular level, PCN instigates apoptosis by mitochondrial intrinsic apoptotic pathway via the overexpression of p53, Bax, cytochrome C release and activation of caspase-3 with the inhibition of oncogenic anti-apoptotic proteins such as PARP and Bcl-2 family proteins (Bcl-2, Bcl-w and Bcl-xL). The in silico docking studies of PCN targeted against the anti-apoptotic members of Bcl-2 family proteins revealed the interaction of PCN with the BH3 domain, which might lead to the induction of apoptosis due to the inhibition of antiapoptotic proteins. Due to its innate inhibition potential of antiapoptotic Bcl-2 family proteins, PCN may be used as potent anticancer agent against both lung and breast cancer.

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“…1), a naturally occurring cyclolignan which is the main component of podophyllum resin, exhibits pronounced biological activities, especially anticancer effects through inhibiting microtubule assembly. [13][14][15][16][17] Herein, we have to note some well-known drugs, GL331 (2), NPF (3), TOP53 (4), and NK611 (5), especially the three most highly prescribed anticancer drugs in the world, etoposide (6), teniposide (7), and the water-soluble prodrug etopophos (8), that base on podophyllotoxin scaffold. [13][14][15][16][17] Herein, we have to note some well-known drugs, GL331 (2), NPF (3), TOP53 (4), and NK611 (5), especially the three most highly prescribed anticancer drugs in the world, etoposide (6), teniposide (7), and the water-soluble prodrug etopophos (8), that base on podophyllotoxin scaffold.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of novel aryl dithian valeryl podophyllotoxin ester derivatives as potential antitubulin agents

Lin

Han

et al. 2015

RSC Adv.

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Microtubules are among the most successful targets for anticancer therapy. In this study, we described the synthesis routes of the lipoyl podophyllotoxin ester derivatives and found that they can selectively inhibit the proliferation of cancer cells without damaging the non-cancer cells. Among them, L4 showed the best antiproliferation activity with IC 50 ¼ 2.68 mM against A549 cells. This effect of L4 was similar to that of CA-4 (IC 50 ¼ 2.78 mM), a typical microtubule inhibitor, but better than podophyllotoxin (IC 50 ¼ 6.57 mM)itself. Furthermore, cell cycle analysis revealed that L4 can remarkably cause cell cycle arrest in the G2/M phase in a time-and dose-dependent manner. But the effect of L4 on apoptosis inducing was not apparent enough. Moreover, confocal microscopy and western blot analysis results indicated that L4 can perturb microtubule polymerization, thus causing tumor growth inhibition.

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4′-Demethyl-deoxypodophyllotoxin glucoside isolated from Podophyllum hexandrum exhibits potential anticancer activities by altering Chk-2 signaling pathway in MCF-7 breast cancer cells

Cited by 43 publications

References 36 publications

Lead Phytochemicals for Anticancer Drug Development

Lead Phytochemicals for Anticancer Drug Development

Phenazine-1-carboxamide (PCN) from Pseudomonas sp. strain PUP6 selectively induced apoptosis in lung (A549) and breast (MDA MB-231) cancer cells by inhibition of antiapoptotic Bcl-2 family proteins

Synthesis of novel aryl dithian valeryl podophyllotoxin ester derivatives as potential antitubulin agents

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