Cytotoxicity of the indole alkaloid reserpine from Rauwolfia serpentina against drug-resistant tumor cells

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology
Sara A A Abdelfatah, Thomas Efferth

Abstract

The antihypertensive reserpine is an indole alkaloid from Rauwolfia serpentina and exerts also profound activity against cancer cells in vitro and in vivo. The present investigation was undertaken to investigate possible modes of action to explain its activity toward drug-resistant tumor cells. Sensitive and drug-resistant tumor cell lines overexpressing P-glycoprotein (ABCB1/MDR1), breast cancer resistance protein (ABCG2/BCRP), mutation-activated epidermal growth factor receptor (EGFR), wild-type and p53-knockout cells as well as the NCI panel of cell lines from different tumor origin were analyzed. Reserpine's cytotoxicity was investigated by resazurin and sulforhodamine assays, flow cytometry, and COMPARE and hierarchical cluster analyses of transcriptome-wide microarray-based RNA expressions. P-glycoprotein- or BCRP overexpressing tumor cells did not reveal cross-resistance to reserpine. EGFR-overexpressing cells were collateral sensitive and p53- Knockout cells cross-resistant to this drug compared to their wild-type parental cell lines. Reserpine increased the uptake of doxorubicin in P-glycoprotein-overexpressing cells, indicating that reserpine inhibited the efflux function of P-glycoprotein. Using molecular docking, we...Continue Reading

References

Nov 11, 1976·Biochimica Et Biophysica Acta·R L Juliano, V Ling
Dec 1, 1989·Journal of the American College of Cardiology·G L Bakris, E D Frohlich
Oct 1, 1984·Japanese Journal of Pharmacology·S WakusawaR Koshiura
Nov 1, 1980·Archives of Toxicology·B E Matter, T Tsuchimoto
Nov 9, 1995·Biochemical Pharmacology·L JettéR Beliveau
Jan 1, 1997·Current Opinion in Oncology·W S el-Deiry
Feb 8, 1957·Science·M BELKIN, W G HARDY
Oct 25, 2003·Oncogene·Wafik S El-Deiry
Sep 24, 2004·Current Topics in Medicinal Chemistry·David J Villeneuve, Amadeo M Parissenti
Jun 19, 2007·Biochimica Et Biophysica Acta·Jean-Pierre GilletJosé Remacle
Apr 17, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Thomas EfferthManfred Volm
May 26, 2009·Peptides·Giuseppina CantarellaRenato Bernardini
Sep 19, 2009·Trends in Pharmacological Sciences·Matthew D HallMichael M Gottesman
Nov 7, 2009·Brazilian Oral Research·Ricardo Carneiro BorraPriscila Maria Andrade
Jan 5, 2011·Chinese Journal of Cancer·Jill WykoskyWebster K Cavenee
Oct 4, 2011·Journal of Ethnopharmacology·Tolga Eichhorn, Thomas Efferth
Jan 25, 2012·Current Cancer Drug Targets·T E TaylorW K Cavenee
May 11, 2012·Planta medica·Thomas Efferth
Oct 6, 2012·The Journal of Toxicological Sciences·Ryo OhtaJun Kanno
Oct 13, 2012·Planta medica·Jing-Jy ChengLie-Chwen Lin
Aug 24, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Ean-Jeong SeoThomas Efferth
Oct 19, 2013·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Yasuhiro TajimaThomas Efferth
Nov 14, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Benjamin KruscheThomas Efferth
Apr 12, 2014·Dermatology Research and Practice·K ChanprapaphP Rattanakaemakorn
Apr 18, 2014·Journal of Molecular Cell Biology·Jun-Ming LiaoHua Lu

❮ Previous
Next ❯

Citations

Jun 21, 2016·Pharmaceuticals·Felix Schmidt, Thomas Efferth
Jun 8, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Saikat DewanjeeMuhammad Zia-Ul-Haq
Apr 29, 2016·The Cochrane Database of Systematic Reviews·Selin Nur, Clive E Adams
May 1, 2018·Oncotarget·Nadire ÖzenverThomas Efferth
Jun 27, 2020·Natural Product Research·Thi-Hoa-Tham PhamThuc-Huy Duong
Apr 13, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Lisa GruberThomas Efferth
Jul 28, 2019·Antimicrobial Resistance and Infection Control·Bahman KhamenehBibi Sedigheh Fazly Bazzaz
Mar 27, 2018·Phytotherapy Research : PTR·Bhushan S BhadaneRavindra H Patil
Aug 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Djenisa H A RochaArtur M S Silva
Jun 10, 2020·Current Topics in Medicinal Chemistry·Rodrigo Santos Aquino de AraújoFrancisco Jaime Bezerra Mendonça-Junior
Apr 2, 2020·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Sara AbdelfatahThomas Efferth
Jun 23, 2020·Current Topics in Medicinal Chemistry·Dan Xu, Zhi Xu
Oct 28, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Caiyan LiuHaiyang Yu
Nov 20, 2020·Bioorganic Chemistry·Onur SerçinoğluBerna Sariyar Akbulut
Feb 13, 2017·European Journal of Medicinal Chemistry·Angela PaternaMaria-José U Ferreira
Aug 10, 2021·Frontiers in Pharmacology·Tushar KhareVinay Kumar

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Cancer -Omics

A variety of different high-throughput technologies can be used to identify the complete catalog of changes that characterize the molecular profile of cohorts of tumor samples. Discover the latest insights gained from cancer 'omics' in this feed.

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Cardiovascular Homeostasis

Cardiovascular regulation and homeostasis is important in maintaining health and dysfunction may lead to cardiovascular diseases. Nitric oxide and vascular endothelium are one of many molecules involved in the homeostatic mechanism. Here is the latest research on cardiovascular homeostasis.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Cardiovascular Risk Reduction

Prevention of cardiovascular disease is an important health initiative. Risk reduction including physical activity, smoking cessation, diet, blood pressure lowering drugs and pharmacotherapy. Here is the latest research on cardiovascular risk reduction.

Antihypertensive Agents: Mechanisms of Action

Antihypertensive drugs are used to treat hypertension (high blood pressure) which aims to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Discover the latest research on antihypertensive drugs and their mechanism of action here.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis