Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode

Gummadi, Venkateshwar Rao; Rajagopalan, Sujatha; Looi, Chung Yeng; Paydar, Mohammadjavad; Renukappa, Girish Aggunda; Ainan, Bharathi Raja; Krishnamurthy, Narasimha Rao; Panigrahi, Sunil K.; Mahasweta, Kumari; Raghuramachandran, Sangeetha; Rajappa, Manoj; Ramanathan, Anuradha; Lakshminarasimhan, Anirudha; Ramachandra, Murali; Wong, Pooi-Fong; Mustafa, Mohammad Rais; Nanduri, Srinivas; Subramanya, Hosahalli

doi:10.1016/j.bmcl.2013.06.071

Cited by 19 publications

(8 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prostate cancer cells (PC3) were cultured in Roswell Park Memorial Institute (RPMI)-1640 medium with 10% fetal bovine serum (FBS) and 1% of 100 unit/mL of penicillin and streptomycin,20 and normal prostate cells (RWPE-1) were cultured in a concentration of 4×10 4 keratinocyte serum-free medium (K-SFM) supplemented with 0.2 ng/mL human epidermal growth factor (rhEGF) and 25 µg/mL bovine pituitary extract (BPE)21 and 1× antibiotic/antimycotic solution. Cultures were incubated at 37°C in a humidified atmosphere containing 5% CO 2 and passed weekly 22–24…”

Section: Methodsmentioning

confidence: 99%

Apoptotic induction and inhibition of NF-κB signaling pathway in human prostatic cancer PC3 cells by natural compound 2,2'-oxybis (4-allyl-1-methoxybenzene), biseugenol B, from <em>Litsea costalis</em>: an in vitro study

Babaei

Huri

Kamalıdehghan

et al. 2017

OTT

View full text Add to dashboard Cite

Litsea is considered as an evergreen genus distributed in tropical and subtropical Asia; this genus belongs to the large family of Lauraceae. In this study, the cell-death metabolism of biseugenol B was investigated. Nuclear condensation, cell permeability, mitochondrial membrane potential (MMP) and release of cytochrome c have been detected in human prostate cancer cell line (PC3) treated with biseugenol B by high content screening (HCS). Fluorescent analysis was conducted to examine the reactive oxygen species formation. To determine the mechanism of cell death, the levels of Bcl-cell lymphoma (Bcl)-2 proteins, Bcl-2-associated X (Bax) protein and anti-apoptosis heat-shock protein 70 were tested by applying reverse transcription polymerase chain reaction and Western blot. Bioluminescent assays were also performed to assess the level of caspases such as 3/7, 8 and 9 during treatment. Furthermore, the involvement of nuclear factor kappa-B (NF-κB) was examined by Western blot and HCS. Biseugenol B showed significant cytotoxicity toward PC3 with no toxicity toward normal prostate cells (RWPE-1), which indicates that biseugenol B has qualities that induce apoptosis in tumor cells. The treatment of PC3 cells with biseugenol B provoked apoptosis with cell-death-transducing signals. Downregulation of Bcl-2 and upregulation of Bax regulated the MMP, which in turn caused the release of cytochrome c from mitochondria into cytosol. The release of cytochrome c activated caspase-9, which consequently activated caspase-3/7 with the cleaved poly(ADP-ribose) polymerase protein, thereby resulting in apoptosis alteration. Involvement of an extrinsic apoptosis pathway was exhibited by the increase in caspase-8, while the increase in caspase-3/7 and caspase-9 demonstrated involvement of an intrinsic apoptosis pathway. Meanwhile, no significant increase was observed in caspases 3/7, 8 or 9 in normal prostate cells (RWPE-1) after treatment with biseugenol B. Prevention of NF-κB translocation from the cytosol to the nucleus occurred in PC3 after treatment with biseugenol B. The results of our study reveal that biseugenol B triggers the apoptosis of PC3 cells via intrinsic and extrinsic apoptosis pathways and inhibition of NF-κB signaling pathway. Our findings suggest that biseugenol B is a potentially useful agent for prostate cancer treatment.

show abstract

Section: Methodsmentioning

confidence: 99%

Apoptotic induction and inhibition of NF-κB signaling pathway in human prostatic cancer PC3 cells by natural compound 2,2'-oxybis (4-allyl-1-methoxybenzene), biseugenol B, from <em>Litsea costalis</em>: an in vitro study

Babaei

Huri

Kamalıdehghan

et al. 2017

OTT

View full text Add to dashboard Cite

show abstract

“…The cytotoxic effect of boldine was assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) cell viability assay 20. The assay was performed for different treatment time points.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of cytotoxic and chemotherapeutic properties of boldine in breast cancer using in vitro and in vivo models

Paydar¹,

Kamalıdehghan²,

Wong³

et al. 2014

DDDT

Self Cite

View full text Add to dashboard Cite

To date, plants have been the major source of anticancer drugs. Boldine is a natural alkaloid commonly found in the leaves and bark of Peumus boldus. In this study, we found that boldine potently inhibited the viability of the human invasive breast cancer cell lines, MDA-MB-231 (48-hour IC50 46.5±3.1 μg/mL) and MDA-MB-468 (48-hour IC50 50.8±2.7 μg/mL). Boldine had a cytotoxic effect and induced apoptosis in breast cancer cells as indicated by a higher amount of lactate dehydrogenase released, membrane permeability, and DNA fragmentation. In addition, we demonstrated that boldine induced cell cycle arrest at G2/M phase. The anticancer mechanism is associated with disruption of the mitochondrial membrane potential and release of cytochrome c in MDA-MB-231. Boldine selectively induced activation of caspase-9 and caspase-3/7, but not caspase-8. We also found that boldine could inhibit nuclear factor kappa B activation, a key molecule in tumor progression and metastasis. In addition, protein array and Western blotting analysis showed that treatment with boldine resulted in downregulation of Bcl-2 and heat shock protein 70 and upregulation of Bax in the MDA-MB-231 cell line. An acute toxicity study in rats revealed that boldine at a dose of 100 mg/kg body weight was well tolerated. Moreover, intraperitoneal injection of boldine (50 or 100 mg/kg) significantly reduced tumor size in an animal model of breast cancer. Our results suggest that boldine is a potentially useful agent for the treatment of breast cancer.

show abstract

“…The cytotoxic effect of PDM was assessed by MTT cell viability assay against different cancer cells [19]. 1.0 × 10 4 cells were seeded in a 96-well plate and incubated overnight at 37°C in 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Persea declinata (Bl.) Kosterm Bark Crude Extract Induces Apoptosis in MCF‐7 Cells via G₀/G₁ Cell Cycle Arrest, Bcl‐2/Bax/Bcl‐xl Signaling Pathways, and ROS Generation

Narrima

Paydar

Looi

et al. 2014

Evidence-Based Complementary and Alternative Medicine

Self Cite

View full text Add to dashboard Cite

Persea declinata (Bl.) Kosterm is a member of the Lauraceae family, widely distributed in Southeast Asia. It is from the same genus with avocado (Persea americana Mill), which is widely consumed as food and for medicinal purposes. In the present study, we examined the anticancer properties of Persea declinata (Bl.) Kosterm bark methanolic crude extract (PDM). PDM exhibited a potent antiproliferative effect in MCF-7 human breast cancer cells, with an IC50 value of 16.68 µg/mL after 48 h of treatment. We observed that PDM caused cell cycle arrest and subsequent apoptosis in MCF-7 cells, as exhibited by increased population at G0/G1 phase, higher lactate dehydrogenase (LDH) release, and DNA fragmentation. Mechanistic studies showed that PDM caused significant elevation in ROS production, leading to perturbation of mitochondrial membrane potential, cell permeability, and activation of caspases-3/7. On the other hand, real-time PCR and Western blot analysis showed that PDM treatment increased the expression of the proapoptotic molecule, Bax, but decreased the expression of prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner. These findings imply that PDM could inhibit proliferation in MCF-7 cells via cell cycle arrest and apoptosis induction, indicating its potential as a therapeutic agent worthy of further development.

show abstract

Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode

Cited by 19 publications

References 12 publications

Apoptotic induction and inhibition of NF-κB signaling pathway in human prostatic cancer PC3 cells by natural compound 2,2'-oxybis (4-allyl-1-methoxybenzene), biseugenol B, from <em>Litsea costalis</em>: an in vitro study

Apoptotic induction and inhibition of NF-κB signaling pathway in human prostatic cancer PC3 cells by natural compound 2,2'-oxybis (4-allyl-1-methoxybenzene), biseugenol B, from <em>Litsea costalis</em>: an in vitro study

Evaluation of cytotoxic and chemotherapeutic properties of boldine in breast cancer using in vitro and in vivo models

Persea declinata (Bl.) Kosterm Bark Crude Extract Induces Apoptosis in MCF‐7 Cells via G₀/G₁ Cell Cycle Arrest, Bcl‐2/Bax/Bcl‐xl Signaling Pathways, and ROS Generation

Contact Info

Product

Resources

About

Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode

Cited by 19 publications

References 12 publications

Apoptotic induction and inhibition of NF-&kappa;B signaling pathway in human prostatic cancer PC3 cells by natural compound 2,2&#39;-oxybis (4-allyl-1-methoxybenzene), biseugenol B, from <em>Litsea costalis</em>: an in vitro study

Apoptotic induction and inhibition of NF-&kappa;B signaling pathway in human prostatic cancer PC3 cells by natural compound 2,2&#39;-oxybis (4-allyl-1-methoxybenzene), biseugenol B, from <em>Litsea costalis</em>: an in vitro study

Evaluation of cytotoxic and chemotherapeutic properties of boldine in breast cancer using in vitro and in vivo models

Persea declinata (Bl.) Kosterm Bark Crude Extract Induces Apoptosis in MCF‐7 Cells via G0/G1 Cell Cycle Arrest, Bcl‐2/Bax/Bcl‐xl Signaling Pathways, and ROS Generation

Contact Info

Product

Resources

About

Apoptotic induction and inhibition of NF-κB signaling pathway in human prostatic cancer PC3 cells by natural compound 2,2'-oxybis (4-allyl-1-methoxybenzene), biseugenol B, from <em>Litsea costalis</em>: an in vitro study

Apoptotic induction and inhibition of NF-κB signaling pathway in human prostatic cancer PC3 cells by natural compound 2,2'-oxybis (4-allyl-1-methoxybenzene), biseugenol B, from <em>Litsea costalis</em>: an in vitro study

Persea declinata (Bl.) Kosterm Bark Crude Extract Induces Apoptosis in MCF‐7 Cells via G₀/G₁ Cell Cycle Arrest, Bcl‐2/Bax/Bcl‐xl Signaling Pathways, and ROS Generation