Key Points
- At elevated dosages, neopetroside-B increases heart cell survival but has detrimental effects on cancer cells in laboratory dishes.
- In mice, neopetroside-B prevents chemotherapy treatment-induced heart scarring.
- When combined with chemotherapy, neopetroside-B significantly reduces tumor volume compared to chemotherapy alone in tumor-bearing mice.
Doxorubicin is a chemotherapeutic used to treat a number of cancers like breast, thyroid, and stomach cancer by inducing cell stress from buildup of unstable molecules called reactive oxygen species. The heart has less antioxidant activity to counter cellular reactive oxygen species accumulation compared to other tissues, making it more prone to doxorubicin-induced damage. The heart damage from this chemotherapeutic typically materializes as tissue scarring, which can lead to heart injury. Finding novel ways to counteract doxorubicin-induced heart injury is of great need.
Published in Biomedicine & Pharmacotherapy, Han and colleagues from Inje University in Korea show that elevated doses of the NAD+ boosting molecule neopetroside-B enhance the survival of human heart cells in laboratory dishes, while negatively impacting cancer cell survival. The researchers go on to show that neopetroside-B treatment prevents doxorubicin chemotherapy-induced heart scarring in mice. Moreover, neopetroside-B significantly reduces tumor volumes when combined with doxorubicin compared to doxorubicin treatment alone in breast cancer tumor-bearing mice. These findings suggest that this NAD+ boosting molecule can protect the heart against a common chemotherapeutic treatment while synergistically improving its anticancer activity.
Neopetroside-B Protects the Heart Against Chemotherapy and Enhances Chemotherapeutic Anticancer Effects
To find out what effect neopetroside-B has on heart and cancer cells, Han and colleagues treated human heart, rat heart, human breast cancer, and human cervical cancer cells with neopetroside-B. Following 20 to 30 minutes of incubation in neopetroside-B, the researchers measured cell survival. They found that neopetroside-B increased the number of human heart cells at higher treatment doses but had no effect on rat heart cells at any dose. Intriguingly, neopetroside-B significantly reduced cell survival for the human breast cancer and human cervical cancer cell lines at higher doses. These findings suggest that neopetroside-B positively influences heart cell survival, while having detrimental effects on cancer.
Since neopetorside-B enhances heart cell survival in laboratory dishes, Han and colleagues sought to find whether the molecule can protect the heart against doxorubicin chemotherapy in living animals, tumor-bearing mice specifically. The research team measured heart scarring (fibrosis), a telltale sign of heart damage from chemotherapy. They found that doxorubicin substantially increased the amount of heart fibrosis but that neopetroside-B prevented it when added to the doxorubicin treatment. These findings show that neopetroside-B protects the heart against fibrosis when combined with doxorubicin treatment.
The Korea-based researchers sought to determine whether the neopetroside-B’s detrimental effects against cancer cells in laboratory dishes translate to tumors in mice. They utilized mice bearing breast cancer tumors and found that, as expected, doxorubicin-treated mice displayed significantly reduced tumor volumes compared to non-treated tumor-bearing mice. Interestingly, when neopetroside-B was combined with doxorubicin treatment, tumor size decreased even more compared to doxorubicin treatment alone. These results suggest an enhanced synergistic effect against cancer when neopetroside-B is combined with doxorubicin chemotherapy.
“We demonstrated that [neopetroside-B] has cardioprotective and anti-cancer effects, which could be associated with NAD+/NADH balance,” said Han and colleagues. “Our study could provide a framework for future research to prevent doxorubicin-induced cardiotoxicity during chemotherapy. Further understanding of the action of [neopetroside-B] could help prevent possible heart failure in cancer chemotherapy with doxorubicin.”
Neopetroside-B’s Potential as an Adjuvant to Chemotherapy
The study not only showed neopetroside-B’s capability to protect the heart against doxorubicin chemotherapy-induced damage but also shows that the NAD+ booster has anti-cancer effects. As such, neopetroside-B could be used as an adjuvant to chemotherapy treatment to help fight cancer.
This is one of only a few studies to suggest that an NAD+-boosting molecule provides anticancer benefits. Future research will need to confirm these findings, and human trials should be pursued to find whether neopetroside-B’s anticancer benefits in mice apply to humans.
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