Strigolactones: A Novel Class of Phytohormones that Inhibit the Growth and Survival of Breast Cancer Cells

Categories: “Cancer Therapeutics“

Reference #: 2012-002

OTC Contact: Zeinab Abouissa. (Directory Information | Send a Message)

Description

Multiple plant hormones (phytohormones) such as Cytokinins and Methyl Jasmonate are known as effective anti-cancer agents. Strigolactones are a novel class of plant hormones and researchers at Georgetown University’s Medical Center have developed novel strigolactone analogues (SLAs) that inhibited the growth and survival of breast, colon, lung, prostate, pancreatic, melanoma, osteosarcoma and leukemia cancer cell lines.

The researchers have shown that the SLAs induced cell cycle arrest and apoptosis leading to a non-reversible reduction in cell viability of pan-cancer cells. The investigators show that SLAs enhance the formation of DNA double strand breaks (DSBs) by interfering with RAD51 binding to DNA and inhibiting DNA DSB repair. Furthermore, the investigators have shown a synergistic effect and increased cancer cell apoptosis of SLAs with PARP inhibitors in cell lines and in pre-clinical models of triple negative breast cancer. In addition, SLAs induced stress response which correlated with phosphorylation of p38 MAPK, JNK1/2 and inhibition of AKT contributing to cells death.

SLAs also synergized with other chemotherapeutic agents such as paclitaxel on breast cancer cells, and Gemcitabine, the most commonly prescribed drug for pancreatic ductal adenocarcinoma (PDAC) patients,
on PDAC cells.

Thus, these strigolactone analogues are promising candidates for board-spectrum anticancer agents due to their ability to specifically inhibit DNA repair, induce cell cycle arrest, cellular stress, and apoptosis in tumor cells with minimal effects on growth and survival of normal cells.

Applications

Applications/Advantages:
 While cancer stem cells contribute to cancer therapy resistance and metastasis, these compounds
showed greater potency inhibiting the growth of cancer stem cell enriched-mammospheres and
other tumorspheres.

 SLAs are highly potent towards stem-like enriched cells of multiple origin.

 SLAs inhibition of DSBs repair contributed to increased genomic instability and potential formation
of neoantigens

 Synergistic effect of these SLAs with other chemotherapeutic agents can potentially permit the use
of the lowest possible drug dosages to effectively target all cancer cells and reduce toxic side effects

The novel compounds are potential therapeutic treatments for breast, lung, colon, and prostrate cancers and may be particularly effective at killing cancer stem cells.

Advantages

Strigolactones represent a new class of anticancer therapeutics.

The strigolactone analogs can induce cell cycle arrest and cell death in breast cancer cells but had little effect on normal cells.

The strigolactone analogs were even more effective at killing cancer stem-like cells at lower doses.

The compounds also demonstrated efficacy at killing colon, lung, and prostate cancer cell lines.

Stage of Development

Studies are now underway using the novel synthetic strigolactone analogs for treatment of mouse models of breast cancer. Preliminary studies indicate that the strigolactone analogs induce activation of stress response pathways and inhibition of PI3K/AKT activation.

Relevant Publications

US Patent No.,10,208,007

Patent Status

European patent application allowed
Canadian patent application pending

Israeli patent application issued