Related Experiment Video

Updated: Mar 17, 2026

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
09:19

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo

Published on: February 6, 2015

9.2K

Anti-cancer effects of nitrogen-containing bisphosphonates on human cancer cells

Pengfei Jiang1, Peiying Zhang2, Rajesh Mukthavaram1

  • 1Moores Cancer Center, UC San Diego, La Jolla, CA 92093, USA.

Oncotarget
|July 28, 2016
PubMed

Insights

Zoledronic acid, a nitrogen-containing bisphosphonate, effectively inhibits glioblastoma and breast cancer cell growth. It works by stimulating autophagy and interfering with cholesterol synthesis, offering potential as an anti-cancer therapy.

Area of Science:

  • Oncology
  • Pharmacology
  • Cell Biology

Background:

  • Nitrogen-containing bisphosphonates (NBPs) like zoledronic acid are used to manage bone turnover in various diseases.
  • Emerging clinical evidence suggests direct anti-cancer properties of zoledronic acid beyond skeletal benefits.

Purpose of the Study:

  • To investigate the anti-proliferative effects of four clinically available NBPs on human tumor cell lines.
  • To elucidate the mechanism of action of zoledronic acid in cancer cells.

Main Methods:

  • Assessed the anti-proliferative effects of NBPs on glioblastoma (GBM) and breast cancer cell lines.
  • Evaluated zoledronic acid's efficacy in GBM xenograft mouse models.
  • Investigated cellular responses including autophagy and apoptosis.
  • Examined the role of the cholesterol synthesis pathway intermediate, geranylgeranyl diphosphate (GGPP), and Rabgeranylgeranyltransferase (RABGGTA) gene knockdown.

Main Results:

  • Zoledronic acid demonstrated potent anti-proliferative activity against GBM and breast cancer cell lines, including patient-derived GBM lines.
  • Zoledronic acid significantly inhibited GBM tumor growth in vivo.
  • The drug strongly induced autophagy but not apoptosis in tested cancer cells.
  • Geranylgeranyl diphosphate (GGPP) rescued cells from zoledronic acid's cytotoxic effects.
  • Knockdown of RABGGTA mimicked the anti-cancer effects of zoledronic acid.

Conclusions:

  • Zoledronic acid exhibits significant direct anti-cancer effects, particularly against glioblastoma.
  • The anti-cancer mechanism involves the induction of autophagy and disruption of Rab protein prenylation via the GGPP pathway.
  • Zoledronic acid shows promise as a potential anti-cancer therapeutic agent.
Keywords:
autophagybisphosphonatescancer therapyglioblastomazoledronic acid

More Related Videos

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

6.6K
Expansion of Human Peripheral Blood γδ T Cells using Zoledronate13:08

Expansion of Human Peripheral Blood γδ T Cells using Zoledronate

Published on: September 9, 2011

28.5K

Related Concept Videos

Cancer Therapies02:49

Cancer Therapies

Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
10.6K
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
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.1K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.9K
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
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
4.2K