Classical and atypical resistance of cancer cells as a target for resveratrol

Sylwia Borska1, Monika Pedziwiatr1, Monika Danielewicz1

  • 1Department of Histology and Embryology, Medical University, 50-368 Wroclaw, Poland.

Oncology Reports
|July 20, 2016
PubMed

Insights

Resveratrol shows promise in overcoming cancer cell resistance to chemotherapy by inhibiting proliferation and affecting key resistance proteins. This natural compound may help sensitize cancer cells to existing anticancer drugs.

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Cancer cell resistance to chemotherapy is a major obstacle in effective anticancer therapy.
  • Identifying agents that can resensitize cancer cells to chemotherapeutics is a critical research area.
  • Resveratrol, a natural polyphenol, exhibits pleiotropic effects on cancer cells and is being investigated for its potential in overcoming drug resistance.

Purpose of the Study:

  • To evaluate the efficacy of resveratrol in inhibiting human pancreatic cancer cell proliferation.
  • To assess the impact of resveratrol on the levels of proteins associated with cytostatic drug resistance.
  • To investigate resveratrol's potential to overcome chemoresistance in specific pancreatic cancer cell lines.

Main Methods:

  • Utilized human pancreatic cancer cell lines with varying resistance profiles (EPP85-181P, EPP85-181RDB, EPP85-181PRNOV).
  • Assessed cell viability and proliferation using the Sulforhodamine B (SRB) assay.
  • Analyzed cell cycle arrest and protein expression (P-glycoprotein, Topoisomerase II α/β) via Flow Cytometry (FACS) and Western blot analysis, respectively.
  • Visualized protein localization using immunofluorescence techniques.

Main Results:

  • Resveratrol demonstrated significant inhibition of proliferation across all tested pancreatic cancer cell lines.
  • Resveratrol reduced the expression and activity of P-glycoprotein (P-gp) in daunorubicin-resistant cells (EPP85-181RDB).
  • A statistically significant increase in both isoforms of Topoisomerase II (TopoII) was observed in mitoxantrone-resistant cells (EPP85-181PRNOV) upon resveratrol treatment.

Conclusions:

  • Resveratrol effectively inhibits pancreatic cancer cell proliferation in vitro.
  • Resveratrol modulates key proteins involved in chemoresistance, including P-glycoprotein and Topoisomerase II.
  • These findings suggest that resveratrol holds potential as an adjuvant therapy to overcome cancer cell resistance to chemotherapeutic drugs.

Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.9K
Treatment Resistent Cancers02:56

Treatment Resistent Cancers

1.5K
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
6.3K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
7.3K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

4.2K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
9.1K