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Cancer

NAD⁺ Boosting Molecule Protects the Heart Against Chemotherapy and Suppresses Cancer: Korean Study

Researchers show treatment with the nicotinamide adenine dinucleotide (NAD+) precursor neopetroside-B increases heart cell survival, prevents chemotherapy-induced heart scarring, and reduces tumor volume in mice.

(The molecular structure of the NAD+ precursor neopetroside-B)
By Bennett M. Sherman

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.

(Yoon et al., 2023 | Biomedicine & Pharmacotherapy) Neopetroside-B enhances human heart cell survival while reducing cancer cell survival. Human heart cells (AC16) showed improved cell survival with higher neopetroside-B doses, while rat heart cells (H9C2) showed no significant differences. Human breast cancer cells (MCF-7) and human cervical cancer cells (HeLa) displayed reduced survival with higher neopetroside-B doses.

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.

(Yoon et al., 2023 | Biomedicine & Pharmacotherapy) Tumor-bearing mice exhibit significantly more heart fibrosis with doxorubicin treatment, but neopetroside-B prevents this fibrosis when combined with doxorubicin. Compared to non-treated mice (black dots), doxorubicin-treated mice (blue dots) displayed increased heart fibrosis. When combined with doxorubicin, neopetroside-B (orange dots) prevented the increased heart fibrosis.

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.

(Yoon et al., 2023 | Biomedicine & Pharmacotherapy) Neopetroside-B enhances doxorubicin chemotherapy’s anticancer benefits to reduce mouse tumor volumes. Compared to non-treated breast cancer tumor-bearing mice (black dots), doxorubicin treatment (blue dots) significantly reduced tumor volumes. Adding neopetroside-B to the doxorubicin treatments (orange dots) significantly reduced tumor volumes compared to doxorubicin treatment alone.

“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.

Model and Dosage

Model: NOD/SCID mice

Dosage: 3.4 mg/kg/day of neopetroside-B injected for three consecutive days

Source

Yoon CS, Nifantiev NE, Yashunsky DV, Kim HK, Han J. Neopetroside-B alleviates doxorubicin-induced cardiotoxicity via mitochondrial protection. Biomed Pharmacother. 2023 Sep;165:115232. doi: 10.1016/j.biopha.2023.115232. Epub 2023 Jul 29. PMID: 37523986.

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