Exploring New Knowledge | U.S. Scholars Confirm: Ganoderic Acid A and DM Regulate the Tumor-Suppressor Gene NDRG2, Inhibiting the Growth of Malignant Meningioma

(Image elements extracted from the journal’s official website; see Source 1 for details.)

Finding an ideal treatment for refractory malignant meningiomas has long been the hope of both physicians and patients; applying single triterpenoid compounds from Ganoderma lucidum to cancer therapy has been the longstanding aspiration of Ganoderma researchers.

Today, these two aspirations have come together thanks to the efforts of the Neuro-Oncology Group within the Department of Neurosurgery at the Medical University of South Carolina and the Brain and Spinal Cord Tumor Program team at Hollings Cancer Center—a cancer center designated by the National Cancer Institute in the United States.

According to a report published online in November 2019 by the team in Clinical and Translational Oncology—the official journal of the Spanish Society of Oncology—both ganoderic acid A and ganoderic acid DM, when used alone, can effectively inhibit the growth of malignant meningiomas and prolong the survival of tumor-bearing mice. The mechanism underlying this effect is associated with the reactivation of the tumor-suppressor gene NDRG2 (see source 2 for details).

Site of Meningioma Development and Treatment Overview

Beneath our scalp lies the skull, and beneath the skull is the meninges. The meninges are a protective membrane that isolates the brain and spinal cord tissues—the central nervous system—from the external environment. This protective membrane consists of three layers; the middle layer, known as the arachnoid membrane, has a structure resembling a spider’s web. A tumor formed by the abnormal proliferation of arachnoid cells is called a meningioma.

Meningiomas are among the most common types of brain tumors; most are benign, and only a small proportion progress to malignant tumors. Malignant meningiomas, however, tend to recur frequently, have a poor prognosis, and offer limited treatment options.

Schematic diagram of meningeal-related structures & CT images of meningiomas

(Source/Wikipedia, see also Source 3)

Ganoderic Acid A and DM

Reactivation of the tumor suppressor gene NDRG2

According to current scientific findings, several genes influence the development, progression, and recurrence of meningiomas. Among these, NDRG2 (N-myc downstream-regulated gene 2), which has tumor-suppressive effects, is one of the key players. NDRG2 is highly expressed in many normal tissues but appears to be largely absent or poorly expressed in meningioma tissues.

The team from the Medical University of South Carolina then analyzed tumor tissues surgically removed from three patients with malignant meningioma, using the protein level of the tumor suppressor gene NDRG2 as an assessment indicator, and compared these results with those obtained from three samples of normal human brain tissue.

The results showed that the NDRG2 protein level in malignant meningioma tissues was only about 40% of that in normal human brain tissue. However, after these tumor tissues were cultured for 72 hours together with ganoderic acid A or ganoderic acid DM (both at a concentration of 25 μM), the expression level of the NDRG2 protein increased to the same level as that in normal human brain tissue.

Ganoderic Acid A and DM

Induce apoptosis in malignant meningioma cells

The researchers also conducted experiments using human malignant meningioma cell lines (IOMM-Lee cells), normal human neural cell lines, and arachnoid cells. These cells were each cultured separately with either ganoderic acid A or ganoderic acid DM at the same doses and for the same durations as before. The results showed that while more than half of the tumor cells underwent apoptosis, the normal neural cells remained completely unaffected.

This indicates that both ganoderic acid A and ganoderic acid DM can exert an inhibitory effect on tumor cells under relatively safe conditions.

The reason these tumor cells are driven to a dead end is that at least seven protein molecules involved in regulating cell survival and proliferation undergo changes in their levels when exposed to ganoderic acid A or ganoderic acid DM. Among these proteins is NDRG2, which has anti-cancer effects.

Ganoderic Acid A and DM

Inhibit tumor growth, prolong survival.

The team also conducted animal experiments: Human malignant meningioma cell lines (IOMM-Lee cells) were implanted into the meningeal region of immunodeficient aged mice to establish an orthotopic cancer animal model. Two weeks later, the mice were administered 10 mg/kg of ganoderic acid A or ganoderic acid DM daily via intravenous injection.

After 14 days of treatment, in the control group that received no treatment, meningiomas were clearly visible on brain MRI images and had a relatively large area. In contrast, in the groups treated with Ganoderma lucidum acid A and Ganoderma lucidum acid DM, the meningiomas were barely detectable on MRI images. Moreover, these tumor tissues showed significantly higher levels of NDRG2 protein—known to be associated with inhibiting cancer cells—and lower levels of ki67 protein, which is linked to inhibiting apoptosis.

The survival times of the two groups of mice also differed significantly. After implanting the malignant meningioma cell line, the control group survived an average of less than 30 weeks, whereas the groups treated with Ganoderic Acid A and Ganoderic Acid DM survived an average of around 50 weeks.

Moreover, the liver function indicator ALP (alkaline phosphatase, an indicator reflecting hepatocellular injury and necrosis) remained at roughly the same level in all three groups of tumor-bearing mice, indicating that the use of ganoderic acid A and ganoderic acid DM does not cause any hepatotoxic side effects.

Chemical structures of Ganoderic Acid A and Ganoderic Acid DM

The application of single ganoderma triterpenes is promising.

The research findings by the team from the Medical University of South Carolina have confirmed that ganoderic acid A and ganoderic acid DM exhibit activity in inducing apoptosis in malignant meningioma cells. Moreover, these two ganoderic triterpenes have been shown to be safe and do not affect the survival of normal cells. This discovery further highlights their potential to inhibit the growth of malignant meningiomas and extend life expectancy in vivo, offering a highly valuable alternative perspective for the treatment of malignant meningiomas, where current therapeutic options are limited.

It is precisely because of the extensive research on Ganoderma lucidum conducted by numerous scholars in the past that we now have this U.S.-based scientific breakthrough, which further advances the medical applications of these two Ganoderma triterpenoids.

The relentless efforts of scientists around the world bear witness to the enduring appeal of Ganoderma lucidum—from ancient times to the present day. Whether in the future we’ll have the opportunity to develop clinical injection formulations of ganoderic acid A and ganoderic acid DM to benefit cancer patients remains to be seen.

Before that, let’s just enjoy some lingzhi mushrooms!

(Editor’s Note: Due to copyright restrictions on the images of research findings in this paper, they cannot be included in the text.)

[Source of Information]

1. Cover of the journal *Clinical and Translational Oncology*: https://www.springer.com/journal/12094; Abstract of the paper: https://link.springer.com/article/10.1007/s12094-019-02240-6

2. A Das, et al. Ganoderic Acid A/DM-induced NDRG2 Over-Expression Suppresses High-Grade Meningioma Growth. Clin Transl Oncol. 2020 Jul;22(7):1138-1145. doi: 10.1007/s12094-019-02240-6. Epub 2019 Nov 15.

3. Source for the location related to the meninges: https://en.wikipedia.org/wiki/Meninges; Source for CT images of meningioma: https://en.wikipedia.org/wiki/Meningioma)

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