Sempervirine stops ovarian cancer cell growth in preclinical studies

Promising findings seen for traditional Chinese medicine plant compound

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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An oversized human hand is seen holding a mouse in a lab, next to a rack with a trio of vials.

Sempervirine, a compound isolated from a plant used in traditional Chinese medicine, inhibited the growth, spread, and development of ovarian cancer cells in cell and animal models in a laboratory.

According to the researchers, the compound’s anticancer abilities appeared related to its ability to block the apelin signaling pathway — which is known to contribute to ovarian cancer development and progression.

“Our study demonstrates for the first time that sempervirine, a natural alkaloid derived from traditional Chinese medicine, possesses significant anti-ovarian cancer activities,” the researchers wrote, noting the compound’s “profound antitumor effects.”

“Further investigations … are warranted to promote the clinical translation of sempervirine as a novel therapeutic for ovarian cancer,” the team wrote.

The study, “Sempervirine inhibits proliferation, invasion and metastasis of ovarian cancer cells and induces ultrastructural changes in vivo,” was published in the Journal of Ovarian Research.

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Ovarian cancer is often asymptomatic early on, and as a result, about three-quarters of patients aren’t diagnosed until they’re at an advanced stage where the cancer has started to spread. The standard treatment for advanced ovarian cancer is surgery to remove as much of the tumor as possible, followed by chemotherapy.

Despite an initial response, advanced ovarian cancer recurs in most cases. Moreover, currently available chemotherapy medications have a wide range of side effects that substantially impact patients’ life quality.

“Therefore, it is imperative to identify novel agents and develop more effective therapies with [fewer] side effects for ovarian cancer [patients],” the researchers wrote.

Natural sources such as plants and marine organisms are a good place to look for new cancer treatments, according to this team of researchers, from Shanghai Jiao Tong University in China. The team noted that more than 60% of anticancer medications come either directly or indirectly from such sources.

Sempervirine is a bioactive compound derived from the traditional Chinese medicinal plant Gelsemium elegans Benth — more commonly known as heartbreak grass.

While the plant overall is poisonous, sempervirine can be extracted from it, and studies have shown that the molecule is toxic to several types of cancer cells, including breast, cervical, testicular, and lymphoma cancers.

Now, the researchers sought to learn more about the potential anti-ovarian cancer properties of sempervirine. To that end, the team examined its effects in cell cultures and mouse models of the gynecological cancer, focusing on ovarian cancer cell development.

The results of this work showed that such treatment dose-dependently inhibited the growth of human ovarian cancer cells in the lab. Further, it suppressed their ability to invade and spread to new areas, known as metastasis.

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Sempervirine found to inhibit ovarian cancer cell growth in mice

In a mouse model of ovarian cancer, ultrasound imaging showed that sempervirine damaged ovarian tumor cells, according to the researchers.

A closer analysis of the tumor tissue also suggested that the treatment led to a number of harmful changes in the cells that overall disrupted the tumor’s normal structure and development.

The researchers indicated that these findings offer “evidence that sempervirine may inhibit tumor growth through detrimental effects on tumor integrity and developmental processes.”

Overall, the anticancer effects of a high dose of sempervirine were similar to the effects of 5-fluorouracil, a standard chemotherapy drug that’s used to treat ovarian cancer.

Sempervirine also showed minimal signs of toxicity in the mice, the team noted.

Our findings provide strong preclinical evidence supporting sempervirine as a promising natural agent for ovarian cancer treatment.

In a series of other experiments, the scientists examined the mechanisms by which sempervirine may be able to target ovarian cancer cells.

Among the effects of sempervirine was an ability to stop ovarian cancer cells from forming protective colonies that help them survive and grow. The compound also induced a cell death pathway called apoptosis, and inhibited the ability of cells to replicate their DNA. Additionally, it altered the activity of genes involved in signaling pathways related to cancer growth.

Importantly, the researchers noted, the treatment reduced levels of proteins related to the apelin signaling pathway — the abnormal activation of which is known to contribute to ovarian cancer development and progression. Apelin signaling helps promote the formation of blood vessels that supply tumors with the nutrients and oxygen they need to survive.

“Our findings provide strong preclinical evidence supporting sempervirine as a promising natural agent for ovarian cancer treatment,” the researchers wrote.

The team noted, however, that more studies are needed to better understand its mechanisms, pharmacological properties, and safety before the treatment could be translated into humans.

“Sempervirine … merits further development through preclinical and clinical studies for the ultimate benefit of ovarian cancer patients,” the team concluded.