A plant alkaloid, veratridine, potentiates cancer chemosensitivity by UBXN2A-dependent inhibition of an oncoprotein, mortalin-2

@article{Abdullah2015APA,
  title={A plant alkaloid, veratridine, potentiates cancer chemosensitivity by UBXN2A-dependent inhibition of an oncoprotein, mortalin-2},
  author={A. Abdullah and S. Sane and Kate A Branick and Jessica L. Freeling and Hongmin Wang and Dong Zhang and K. Rezvani},
  journal={Oncotarget},
  year={2015},
  volume={6},
  pages={23561 - 23581}
}
Veratridine (VTD), an alkaloid derived from the Liliaceae plant shows anti-tumor effects; however, its molecular targets have not been thoroughly studied. Using a high-throughput drug screen, we found that VTD enhances transactivation of UBXN2A, resulting in upregulation of UBXN2A in the cytoplasm, where UBXN2A binds and inhibits the oncoprotein mortalin-2 (mot-2). VTD-treated cancer cells undergo cell death in UBXN2A- and mot-2-dependent manners. The cytotoxic function of VTD is grade… Expand
Relevance of mortalin to cancer cell stemness and cancer therapy
TLDR
It is reported that upregulation of mortalin contributes to cancer cell stemness and low doses of anti-mortalin molecules caused similar sensitization of cancer cells to chemotherapeutic drugs and hence are potential candidates for effective cancer chemotherapy. Expand
Structural studies of UBXN2A and mortalin interaction and the putative role of silenced UBXN2A in preventing response to chemotherapy
TLDR
Details are provided into the mechanistic role of UBXN2A as a potent mortalin inhibitor and as a potential chemotherapy sensitizer for clinical application and how three amino acids within the substrate-binding domain of mortalin are crucial for UBxN 2A binding to mortalin. Expand
UBXN2A enhances CHIP‐mediated proteasomal degradation of oncoprotein mortalin‐2 in cancer cells
TLDR
The existence of a multiprotein complex containing UBXN2A, CHIP, and mot‐2 suggests a synergistic tumor suppressor activity of UBxN 2A and CHIP in mot‐ 2‐enriched tumors, and validates the UB XN2a‐CHIP axis as a novel and potential therapeutic target in CRC. Expand
Nucleocytoplasmic Translocation of UBXN 2 A Is Required for Apoptosis during DNA Damage Stresses in Colon Cancer Cells
The subcellular localization, expression level, and activity of anti-cancer proteins alter in response to intrinsic and extrinsic cellular stresses to reverse tumor progression. The purpose of thisExpand
Neurotoxicity of Veratrum nigrum L. and the molecular mechanism of veratridine toxicity
Veratrum nigrum L. has been used as an herbal preparation in worldwide for treatment of blood-stroke, excessive phlegm, epilepsy, etc. Veratridine is both active and toxic constituents of VeratrumExpand
Antiproliferative effects of combinational therapy of Lycopodium clavatum and quercetin in colon cancer cells
TLDR
The synergistic effect between Lycopodium and quercetin might bring forward the enhanced antitumorigenic properties of combinational therapy with natural products to successfully combat the cancer progression with minimal side effects and resistance to drugs. Expand
Molecular Chaperones in Cancer Stem Cells: Determinants of Stemness and Potential Targets for Antitumor Therapy
TLDR
The present review is dedicated to the implication of molecular chaperones (protein regulators of polypeptide chain folding) in both the formation/maintenance of the CSC phenotype and cytoprotective machinery allowing CSCs to survive after drug or radiation exposure and evade immune attack. Expand
Therapeutic potency of heat-shock protein-70 in the pathogenesis of colorectal cancer: current status and perspectives.
TLDR
This review summarizes the different tumorigenic properties of H SP70 and the potential therapeutic potency of HSP70 inhibitors in terms of a novel strategy for colorectal cancer therapy, for a better understanding, and hence better management of this disease. Expand
Hsp70 inhibitors: Implications for the treatment of colorectal cancer
TLDR
Current knowledge on the progress made so far to discover compounds, which target the Hsp70 family, with particular emphasis on their efficacy in treatment of CRC are summarized. Expand
Current report of natural product development against breast cancer stem cells.
TLDR
Those natural products posses as novel therapeutic agents for breast cancer stem cells eradication and lead compound for the development of breast cancerstem cells-targeted drug are discussed. Expand
...
1
2
...

References

SHOWING 1-10 OF 78 REFERENCES
Difluorinated-Curcumin (CDF): A Novel Curcumin Analog is a Potent Inhibitor of Colon Cancer Stem-Like Cells
TLDR
Diflourinated-curcumin (CDF), a novel analog of the dietary ingredient of curcumin, in combination with 5-fluorouracil and oxaliplatin (5-FU + Ox), the mainstay of colon cancer chemotherapeutic, would be effective in eliminating colon CSCs. Expand
MKT-077, a novel rhodacyanine dye in clinical trials, exhibits anticarcinoma activity in preclinical studies based on selective mitochondrial accumulation.
TLDR
MKT-077 is the first delocalized lipophilic cation with a favorable pharmacological and toxicological profile in preclinical studies and is now being investigated in Phase I clinical trials. Expand
Selective toxicity of MKT-077 to cancer cells is mediated by its binding to the hsp70 family protein mot-2 and reactivation of p53 function.
TLDR
It is reported that MKT-077 binds to an hsp70 family member, mortalin (mot-2), and abrogates its interactions with the tumor suppressor protein, p53, and induced release of wild-type p53 from cytoplasmically sequestered p53-Mot-2 complexes and rescued its transcriptional activation function. Expand
Mitochondria: a promising target for anticancer alkaloids.
TLDR
This review describes mitochondria as a central component in the anticancer action of a set of alkaloids, in a way to illustrate the importance of this organelle in medicinal chemistry. Expand
Stress chaperones, mortalin, and pex19p mediate 5-aza-2' deoxycytidine-induced senescence of cancer cells by DNA methylation-independent pathway.
  • N. Widodo, C. Deocaris, +7 authors S. Kaul
  • Biology, Medicine
  • The journals of gerontology. Series A, Biological sciences and medical sciences
  • 2007
TLDR
Both mortalin and Pex19p are important mediators, prognostic indicators, and tailoring tools for 5AZA-dC-induced senescence in cancer cells. Expand
Induction of apoptosis in prostatic tumor cell line DU145 by staurosporine, a potent inhibitor of protein kinases
TLDR
It is demonstrated that programmed cell death can be induced in an androgen‐independent prostatic cancer cell line and BCL‐2 was found not to play an important role in preventing STS‐induced apoptosis in the DU145 cell line. Expand
Mortalin–p53 interaction in cancer cells is stress dependent and constitutes a selective target for cancer therapy
TLDR
It is demonstrated that the mortalin–p53 interaction exists in cancer cells that are either physiologically stressed (frequently associated with p53 mutations) or treated with stress-inducing chemicals. Expand
Targeting GRP75 Improves HSP90 Inhibitor Efficacy by Enhancing p53-Mediated Apoptosis in Hepatocellular Carcinoma
TLDR
It is shown that the HSP90 inhibitor 17-AAG can induce the expression of GRP75, a member of heat shock protein 70 (HSP70) family, which attenuates the anti-growth effect of H SP90 inhibition on cancer cells and increases p53-mediated inhibition of tumor growth in vivo. Expand
Withanone binds to mortalin and abrogates mortalin-p53 complex: computational and experimental evidence.
TLDR
A molecular interaction basis that could be used for screening and development of anticancer drugs with low toxicity to normal cells is established and accurate knowledge of the 3D structure of mortalin would further enhance the potential of such analyses to understand the molecular basis ofmortalin biology and mortalin based cancer therapy. Expand
Ubiquitin-like (UBX)-domain-containing protein, UBXN2A, promotes cell death by interfering with the p53-Mortalin interactions in colon cancer cells
TLDR
UBXN2A is introduced as a home defense response protein, which can reconstitute inactive p53-dependent apoptotic pathways and inhibit the binding between mot-2 and p53, which is an attractive therapeutic strategy in mot- 2-elevated tumors. Expand
...
1
2
3
4
5
...